| |
Important Note: The following information
is provided for your education. It should not be relied upon
for personal diagnosis or treatment. If you believe that a particular
therapy applies to you or someone you care about, be sure to
consult a doctor before trying it.
Anemia Research: 2002-2006
Am J Kidney Dis. 2006 Sep;48(3):445-55.
Once-every-2-weeks and once-weekly epoetin beta regimens:
equivalency in hemodialyzed patients.
Mircescu G, Garneata L, Ciocalteu A, Golea O, Gherman-Caprioara M, Capsa D, Mota
E, Gusbeth-Tatomir P, Ghenu A, Baluta S, Constantinovici N, Covic AC.
Dr. Carol Davila Teaching Hospital of Nephrology.
BACKGROUND: Currently, less frequent than once-weekly subcutaneous epoetin
administration regimens were shown to be equally effective and safe as
once-weekly schedules in stable predialysis and peritoneal dialysis patients.
Bioequivalency of once-every-2-weeks and once-weekly subcutaneous administration
of the same total dose of epoetin beta for the maintenance phase of anemia
treatment in stable iron-replete long-term hemodialysis patients therefore was
investigated prospectively. METHODS: Two hundred seven stable selected
hemodialysis patients without diabetes, acute illness, significant inflammation,
malnutrition or hyperparathyroidism administered once-weekly subcutaneous
epoetin beta and preserving stable hemoglobin levels between 10 and 12 g/dL (100
and 120 g/L; difference between maximum and minimum of 3 subsequent levels
<or=2.5 g/dL [<or=25 g/L]) and optimal iron status for at least 8 weeks before
inclusion were enrolled and randomly assigned to subcutaneous administration of
the same total dose of epoetin beta either once every 2 weeks (group 2w; n =
104) or once weekly (group 1w; n = 103) for 24 weeks. RESULTS: Per-protocol
analyses (group 1w = 102 versus group 2w = 101) showed similar hemoglobin levels
throughout the assessment period (weeks 13 to 24): mean, 11.38 g/dL; 95%
confidence interval (CI), 11.23 to 11.54 versus 11.41 g/dL; 95% CI, 11.22 to
11.58. Mean difference was 0.028 g/dL (95% CI, -0.208 to 0.264) in the
prespecified range (+/-0.5 g/dL). Epoetin dose ratio of group 2w to group 1w was
0.94 (95% CI, 0.813 to 1.076), also in the prespecified range of equivalence
(0.80 to 1.25). Hemoglobin levels and epoetin doses were stable during the study
irrespective of treatment schedule, with no differences between groups at any
time. Both schedules were well tolerated. CONCLUSION: Once-every-2-weeks and
once-weekly subcutaneous epoetin beta regimens are equivalent in the maintenance
phase of anemia treatment in long-term stable hemodialysis patients without
diabetes, with similar safety profiles.
-----
Health Qual Life Outcomes. 2006 Aug 31;4(1):59 [Epub ahead of print]
Hydroxyurea and sickle cell anemia: Effect on quality of life.
Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH, Koshy M,
Barton BA, Bonds DR, Msh IO.
ABSTRACT: BACKGROUND: The Multicenter Study of Hydroxyurea (HU)
in Sickle Cell Anemia (MSH) previously showed that daily oral HU
reduces painful sickle cell (SS) crises by 50% in patients with
moderate to severe disease. The morbidity associated with this
disease is known to have serious negative impact on the overall
quality of life (QOL) of affected individuals. METHODS: The data
in this report were collected from the 299 patients enrolled in
the MSH. Health quality of life (HQOL) measures were assessed in
the MSH as a secondary endpoint to determine if the clinical
benefit of HU could translate into a measurable benefit
perceptible to the patients. HQOL was assessed with the Profile
of Mood States, the Health Status Short Form 36 (SF-36),
including 4-week pain recall, and the Ladder of Life,
self-administered twice 2-weeks apart pre-treatment and every 6
months during the two-year, randomized, double-blind, treatment
phase. The effects of factors including randomized treatment,
age, gender, pre-treatment crises frequency, Hb-F level mean,
daily pain from 4-week pre-treatment diaries, and 2-year Hb-F
response level (low or high) were investigated. RESULTS: Over
two years of treatment, the benefit of HU treatment on QOL,
other than pain scales, was limited to those patients taking HU
who maintained a high HbF response, compared to those with low
HbF response or on placebo. These restricted benefits occurred
in social function, pain recall and general health perception.
Stratification according to average daily pain prior to
treatment showed that responders to HU whose average daily pain
score was 5-9 (substantial pain) achieved significant reduction
in the tension scale compared to the placebo group and to
non-responders. HU had no apparent effect on other QOL measures.
CONCLUSION: Treatment of SS with HU improves some aspects of QOL
in adult patients who already suffer from moderate-to-severe SS.
-----
Oncology (Williston Park). 2006 Jul;20(8 Suppl 6):39-43.
Erythropoiesis-stimulating protein support and
survival.
Crawford J.
Division of Medical Oncology, Duke Comprehensive Cancer Center,
Durham, North Carolina 27710-0001, USA. crawf006@mc.duke.edu
Anemia is common in many patients with cancer treated with
chemotherapy. One option for managing chemotherapy-induced
anemia (CIA) is erythropoiesis-stimulating proteins (ESPs),
which are indicated for the treatment of CIA in patients with
most types of cancer. They have been shown to be safe and
effective in numerous well-documented studies, and their side
effects are well known. The rate of thrombotic events with the
long-acting ESP darbepoetin alfa (Aranesp) has been consistent
in studies conducted before and after its approval. The
association of thrombotic events with high hemoglobin levels or
rapid increases in its levels in patients with cancer remains
controversial. Adjusting the dose of the ESP to maintain and
monitor a target hemoglobin level of 11 to 12 g/dL is certainly
prudent and may help prevent or minimize these events.
Chemotherapy-induced anemia has been associated with shorter
survival in patients with cancer, and the relation is likely
multifactorial. Data on the treatment of CIA with ESPs have not
shown a consistent effect on survival. Two studies in patients
with hemoglobin levels above the target level showed that
survival was shorter in the patients treated with ESPs. A review
of data from other trials found no effect of ESPs on survival,
and other trials suggested a positive effect. This article
reviews data on survival in patients treated with ESPs and
discusses five large randomized controlled trials of darbepoetin
alfa that are addressing this issue.
-----
Oncology (Williston Park). 2006 Jul;20(8 Suppl 6):8-11.
Management of anemia in patients with hematologic
malignancies.
Straus DJ.
Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New
York, New York, USA. strausd@mskcc.org
Anemia is common in patients with hematologic malignancies, and
it has negative effects on their quality of life. The current
clinical practice guidelines recommend erythropoietic therapy in
patients with cancer- or chemotherapy-related anemia, but anemia
is often undertreated in patients with hematologic malignancies.
Several randomized controlled trials have shown that treatment
with erythropoiesis-stimulating proteins such as epoetin alfa (Procrit),
epoetin beta, and darbepoetin alfa (Aranesp) increases
hemoglobin levels, reduces the need for red blood cell
transfusions, and improves quality of life in patients with
hematologic malignancies and anemia receiving chemotherapy.
Furthermore, preliminary data from a recent open-label study
suggest that early treatment of mild anemia in patients with
hematologic malignancies treated with chemotherapy produces
marked improvements in quality of life and productivity.
Increasing patients' hemoglobin levels may also improve their
cognitive function. These findings support the use of
erythropoietic therapy to manage anemia in patients with
hematologic malignancies who are treated with chemotherapy.
-----
Oncology (Williston Park). 2006 Jul;20(8 Suppl 6):29-32.
Optimizing the dose and schedule of darbepoetin
alfa in patients with chemotherapy-induced anemia.
Glaspy J.
Clinical Research Unit, UCLA School of Medicine, Los Angeles,
California 90095-7077, USA. jglaspy@mednet.ucla.edu
Chemotherapy-induced anemia is common in patients who have
cancer. Erythropoiesis-stimulating proteins such as epoetin alfa
(Procrit) and darbepoetin alfa (Aranesp) have been shown to
improve hematologic and clinical outcomes in these patients.
Darbepoetin alfa has a longer serum half-life than epoetin alfa,
making less frequent administration possible and offering the
possibility of synchronizing the administration of
erythropoietic therapy and chemotherapy. Several clinical trials
have evaluated the utility of darbepoetin alfa given every 3
weeks (q3wk) in patients with chemotherapy-induced anemia. An
exploratory study showed that darbepoetin alfa q3wk stabilized
hemoglobin levels and reduced transfusion requirements. It was
also shown that giving darbepoetin alfa q3wk at the same time as
the chemotherapy produced hematopoietic benefits similar to
those observed when it is given later in the chemotherapy cycle.
The q3wk dosing schedule was effective in patients with mild and
moderate anemia, and treatment goals were achieved in most of
them. The equivalence of q3wk and qwk darbepoetin alfa has also
been established. Synchronous administration of darbepoetin alfa
with chemotherapy is a convenient option for patients with
chemotherapy-induced anemia, with clinical trials showing it to
be an effective treatment strategy.
-----
Oncology (Williston Park). 2006 Jul;20(8 Suppl 6):21-4.
The role of intravenous iron in cancer-related
anemia.
Henry DH.
Department of Medicine, Pennsylvania Hospital, Philadelphia,
Pennsylvania 19106, USA. dhhenry@juno.com
Patients with cancer may have an absolute or functional iron
deficiency as a result of their disease or its treatment. These
conditions can lead to an insufficient supply of iron for
incorporation into erythrocytes during supportive care with
erythropoiesis-stimulating proteins for chemotherapy. The use of
supplemental iron therapy is well established in patients with
chronic kidney disease and anemia, but less well studied in the
oncology/hematology setting. Furthermore, the use of oral iron
formulations in patients with cancer and anemia is limited by
poor absorption in the duodenum, arduous dosing requirements
(three times a day), and a high likelihood of gastrointestinal
side effects. Two recent studies have shown that intravenous (i.v.)
iron (iron dextran or ferric gluconate) increases the
hematopoietic response rates in cancer patients who were
receiving chemotherapy and treated with epoetin alfa (Procrit)
for anemia. The effects on hemoglobin levels and measures of
iron metabolism were notably greater with i.v. iron formulations
than with oral iron formulations. The results from several
ongoing trials of i.v. iron in patients treated with epoetin
alfa or darbepoetin alfa (Aranesp) for chemotherapy-induced
anemia should lead to a greater understanding of the role of i.v.
iron supplementation in improving the hematopoietic responses in
these patients.
-----
Oncology (Williston Park). 2006 Jul;20(8 Suppl 6):16-20.
Benefits of early intervention with
erythropoiesis- stimulating proteins in chemotherapy-induced
anemia.
Lyman GH.
Health Services and Outcomes Research, James P. Wilmot Cancer
Center, University of Rochester Medical Center, Rochester, New
York 14642, USA. gary_lyman@urmc.rochester.edu
Anemia is common in patients treated with chemotherapy for both
solid and hematologic malignancies, contributing to fatigue and
diminished quality of life and exposing them to the inherent
risks of red blood cell transfusions. Erythropoiesis-stimulating
proteins have been shown to increase hemoglobin levels, reduce
the need for transfusions, and improve quality of life. The
current practice guidelines recommend treating moderate to
severe chemotherapy-induced anemia with erythropoiesis-stimulating
proteins, but the risk of transfusions may be less with earlier
intervention at higher hemoglobin levels. A review of the
literature suggests that treating mild chemotherapy-induced
anemia with erythropoiesis-stimulating proteins reduces the
risks of transfusions and the development of more-severe anemia.
Weighing the clinical evidence together with other clinical and
economic considerations should provide greater insight into the
benefits of treating mild anemia in patients treated with
chemotherapy.
-----
Biochem Cell Biol. 2006 Jun;84(3):377-380.
Oral administration of lactoferrin increases
hemoglobin and total serum iron in pregnant women.
Paesano R, Torcia F, Berlutti F, Pacifici E, Ebano V, Moscarini
M, Valenti P.
Department of Obstetrician and Gynecology, University of Rome
"La Sapienza", Via di Grottarossa 1035, 00189 Roma, Italy.
Iron deficiency anemia (IDA) during pregnancy continues to be of
world-wide concern. IDA is a risk factor for preterm delivery
and subsequent low birth weight, and possibly for poor neonatal
health. Iron supplementation in pregnancy is a widely
recommended practice, yet intervention programs have met with
many controversies. In our study, 300 women at different
trimesters of pregnancy were enrolled in a trial of oral
administration of ferrous sulfate (520 mg once a day) or 30%
iron-saturated bovine lactoferrin (bLf) (100 mg twice a day).
Pregnant women refusing treatment represented the control group.
In this group hemoglobin and total serum iron values measured
after 30 d without treatment decreased significantly, especially
in women at 18–31 weeks of pregnancy. In contrast, after
30 d of oral administration of bLf, hemoglobin and total serum
iron values increased and to a greater extent than those
observed in women treated orally for 30 d with ferrous sulfate,
independently of the trimester of pregnancy. Unlike ferrous
sulfate, bLf did not result in any side effects. These findings
lead us to hypothesize that lactoferrin could influence iron
homeostasis directly or through other proteins involved in iron
transport out of the intestinal cells into the blood.
-----
J Am Soc Nephrol. 2006 Apr;17 Suppl 2:S74-7.
Update on erythropoietin treatment: should hemoglobin be
normalized in patients with chronic kidney disease?
Paoletti E, Cannella G.
Address correspondence to: Dr. Ernesto Paoletti, Divisione di Nefrologia,
Dialisi e Trapianto, Azienda Ospedaliera Universitaria San Martino, Genova,
Italy. ernesto.paoletti@hsanmartino.it.
The partial correction of ESRD anemia by recombinant human erythropoietin (EPO)
has resulted both in generalized improvement in quality of life and physical
activity and in reduced mortality and hospitalization rate. The question remains
as to whether normalizing hemoglobin (Hgb) is desirable in patients with chronic
kidney disease (CKD). This review provides an analysis and commentary on the
available reports and, for the most part, randomized, controlled trials on the
topic. In dialysis patients, normalization of Hgb is associated with improved
quality of life and exercise capacity but not with reduced mortality and
hospitalization rate. Moreover, no significant changes in the degree of left
ventricular hypertrophy have been demonstrated. By contrast, an increased
mortality rate has been reported for hemodialysis patients with overt
cardiovascular disease (CVD) when randomly assigned to normal hematocrit by EPO.
Data regarding patients who have CKD but are not yet on renal replacement
therapy are scarce, and the effects of EPO on renal disease progression require
further elucidation through controlled trials. The conclusion that can be drawn
from the available studies is that Hgb >11 g/dl is the minimum required to
achieve improved quality of life in patients with CKD, whereas values >12 g/dl
are not recommended for patients with overt CVD. Finally, Hgb normalization
might reasonably be restricted to a selected population of younger, employed,
and active individuals, provided that they do not have CVD.
-----
Am J Kidney Dis. 2006 Apr;47(4):644-54.
Effect of intravenous ascorbic acid in hemodialysis patients with
EPO-hyporesponsive anemia and hyperferritinemia.
Attallah N, Osman-Malik Y, Frinak S, Besarab A.
Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI 48202,
USA. nattall1@hfhs.org
BACKGROUND: Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis
patients most commonly results from iron deficiency, the contributory role of
chronic inflammation and oxidative stress in its pathogenesis is poorly
understood. We conducted an open-label prospective study to assess the effect of
vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients
with unexplained hyperferritinemia. METHODS: Forty-six of 262 patients in an
inner-city hemodialysis center met the inclusion criteria (administration of
intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk,
average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L],
ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] <
or = 50%). Patients were excluded if they had a clear explanation for the EPO
hyporesponsiveness. Four patients refused to participate. The remaining patients
were randomly assigned; 20 patients to receive standard care and 300 mg of
intravenous vitamin C with each dialysis session (group 1) and 22 patients to
receive standard care only (group 2). Study duration was 6 months. During the
study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from
final analysis. Monthly assessment included Hb level, mean corpuscular volume,
iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in
reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive
protein (CRP), and liver enzymes were measured every 3 months. RESULTS: Age,
sex, race, and time on dialysis therapy were similar in both groups. At 6
months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0
g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P =
0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group
2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk),
iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7
versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL)
decreased significantly in group 1, but not in controls. Changes in Hb content
in reticulocytes and ferritin level also were statistically significant in group
1. There was no change in biointact parathyroid hormone levels. Although serum
iron levels and intravenous iron doses changed within each group, changes were
equal between the 2 groups. CONCLUSION: In hemodialysis patients with refractory
anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either
by augmenting iron mobilization from its tissue stores or through antioxidant
effects.
-----
J Support Oncol. 2006 Mar;4(3):129-35.
Weekly epoetin alfa treatment of anemia in patients with cancer
not undergoing therapy.
Shasha D, Williams D.
Blitman Department of Radiation Oncology, Beth Israel Medical Center, New York,
New York 10003, USA. dshasha@bethisraelny.org
Epoetin alfa is an established treatment of anemia in patients with cancer who
are receiving chemotherapy with or without radiation therapy. However, fewer
data support its use in patients with cancer not currently receiving either
therapy. This 16-week, open-label, nonrandomized, multicenter pilot study
evaluated the clinical profile of epoetin alfa (40,000 U) administered weekly
via subcutaneous injection in anemic patients with cancer not receiving
chemotherapy or radiation therapy. The primary endpoint was the proportion of
patients who achieved a minor (hemoglobin [Hgb] increase > or = 1-1.9 g/dL) or
major (Hgb increase > or = 2 g/dL) hematologic response. The trial was
temporarily suspended to amend the protocol to reflect updated package insert
recommendations for target Hgb and dose adjustments. Of the 98 patients
enrolled, 91 (mean age, 69.5 +/- 9.5 years; baseline Hgb level, 10.4 +/- 0.7 g/dL)
were evaluated for efficacy in a modified intent-to-treat analysis. Nearly all
patients (94.5% [86/91]) achieved a minor response, and the majority (80.2%
[73/91]) achieved a major hematologic response at any time during the study.
Mean Hgb levels increased steadily over the 12-week dosing period, with
significant (P < 0.001) increases from baseline observed as early as week 2.
Only one patient required a transfusion. Epoetin alfa was safe and well
tolerated.
-----
Fut Oncol. 2006 Feb;2(1):21-38.
Epoetin beta in oncology: examining the current evidence.
Ludwig H.
1st Department of Medicine, Center for Oncology and Hematology,
Wilhelminenspital, Montleartstr. 37, A-1171 Vienna, Austria. heinz.ludwig@wienkav.at.
Anemia is highly prevalent in patients with cancer and its impact on quality of
life and long-term outcome in these patients is well documented. Recombinant
human erythropoietins, or epoetins, have been used to treat cancer-related or
antitumor therapy-induced anemia for many years. Through a combination of
clinical studies and extensive experience in the real-life clinical setting,
epoetin beta has been shown to be efficacious and well tolerated, increasing
hemoglobin levels, reducing the need for transfusion and improving quality of
life. This favorable efficacy and safety profile has been demonstrated across a
broad range of malignancy types, irrespective of the treatment used (platinum or
nonplatinum based). The effect of treatment with epoetin beta is rapid, with
mean hemoglobin increases of 1 g/dl seen as early as 4 weeks following the start
of therapy. Furthermore, there is no evidence that epoetin beta negatively
affects overall survival or tumor progression in anemic patients with cancer.
The approved 30,000 IU once-weekly dosing regimen (as opposed to the 10,000 IU
three-times weekly regimen) provides greater convenience and may result in
improved treatment compliance.
-----
Medicina (B Aires). 2006;66(1):51-69.
[Human recombinant erythropoietin therapy]
[Article in Spanish]
Donato H, Ferro H.
Departamento de Neonatologia, Sanatorio de la Trinidad. hugodonato@aol.com
Recombinant human erythropoietin (rHuEpo) has become the most widely used
cytokine in the world. Following the success of its use in patients with
end-stage renal disease, the usefulness of rHuEpo to ameliorate other anemias
was assessed, including pediatric patients and newborn infants. The treatment or
prevention of anemia of prematurity with rHuEpo resulted in a significant
reduction in the number of transfusions and donor exposure. A clear definition
of which premature babies must receive therapy needs yet to be established.
Other indications in neonatal period include hyporegenerative and hemolytic
anemias. With the exception of chronic renal failure, in older children the
efficacy of rHuEpo has not been evaluated as in adults. While an impressive
amount of studies were carried out during the last years in adult patients with
cancer-related or HIV-infection-related anemias, allowing to establish clear
conclusions on its efficacy, only a few trials with small number of patients
have been reported in children. Up to date, results in pediatric patients
suggest that rHuEpo therapy is as useful as in adult patients, but prospective,
randomized trials including large number of patients are essential to achieve
definitive conclusions. Results of studies designed to evaluate the efficacy of
rHuEpo for sustaining an adequate dose of ribavirin in patients receiving
treatment for hepatitis C are encouraging. The potential for use of the non-hematopoietic
effects of rHuEpo in newborn infants is a novel and exciting issue. The role of
rHuEpo as a tissue protective factor for central nervous system and intestinal
mucosa is under exhaustive investigation.
-----
Kidney Blood Press Res. 2005;28(5-6):363-71. Epub 2006 Mar 7.
Anemia management in chronic heart failure: lessons learnt from
chronic kidney disease.
Besarab A, Soman S.
Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI 48202,
USA. abesarab@ghsrenal.com
The importance of anemia in chronic kidney disease (CKD) has become increasingly
well recognized over recent years, as have the benefits of treating anemic CKD
patients with recombinant human erythropoietin (rHuEPO, epoetin). As well as
reducing the need for blood transfusions and the complications associated with
renal failure in CKD patients, rHuEPO treatment decreases patient morbidity and
mortality, particularly as a result of cardiovascular disease. The strong
correlation between anemia, renal failure and cardiac failure is one that has
received much attention recently, with each factor recognized to cause the other
to worsen in a 'vicious cycle'. Recent studies have concentrated on the possible
benefits of anemia treatment in patients with CHF. Currently available data
suggest improvements in CHF symptoms, left ventricular ejection fraction (LVEF)
and a reduction of hospitalizations associated with anemia correction through
epoetin treatment. Available data from CKD patients suggest that anemia
management should begin as early as possible, although the optimal target level
for individual patients is as yet unclear. In addition to the currently
available evidence, additional large, randomized, controlled studies are
required to further define the morbidity/mortality benefits of epoetin treatment
in CHF patients with anemia. Copyright 2005 S. Karger AG, Basel.
-----
Eur J Obstet Gynecol Reprod Biol. 2005 Dec;123 Suppl 2:S3-S13.
Iron deficiency and anaemia in pregnancy: Modern aspects of
diagnosis and therapy.
Breymann C.
The prevalence of iron-deficiency anemia in different regions of the world
ranges from 12 to 43%. The increased iron requirement in pregnancy and the
puerperium carry with it an increased susceptibility to iron deficiency and
iron-deficiency anemia and perioperative or peripartal blood transfusion.
Prevention and correction presuppose reliable laboratory parameters and a
thorough understanding of the mechanisms of iron therapy. The Hb level alone is
insufficient to guide management. A complete work-up (ferritin, transferrin
saturation) is essential, preferably with hematological indices such as
hypochromic and microcytic red cells and reticulocytes, classified by degree of
maturity, in particular, before parenteral therapy is given. Since ferritin acts
as both an iron-storage and acute-phase protein, it cannot be used to evaluate
iron status in the presence of inflammation. A high ferritin level thus requires
the presence fo an inflammatory process to be eliminated before it can be taken
at face value. If the C-reactive protein level is also raised, the soluble TfR
concentration can be used, since it is unaffected by inflammation. Inadequate
understanding of the complex chemistry of parenteral iron administration was
previously responsible for serious side effects, such as toxic and allergic
reactions, and even anaphylactic shock, in particular with dextran preparations.
However, the current type II iron complexes that release iron to the endogenous
iron-binding proteins with a half-life of about 6 hours are not only effective
but carry a minimal risk of allergic accident and overload, especially after a
comprehensive pretreatment work-up. Our departmental data collected over 8 years
and backed by postmarketing experience in 25 countries indicate that iron
sucrose complex therapy is a valid first-line option for the safe and rapid
reversal of iron-deficiency anemia.
-----
Eur J Obstet Gynecol Reprod Biol. 2005 Dec;123 Suppl 2:S21-7.
Severe anaemia in the immediate post-partum period. Clinical
practice and value of intravenous iron.
Broche DE, Gay C, Armand-Branger S, Grangeasse L, Terzibachian JJ.
Department of Obstetrics and Gynaecology, Regional Hospital, 14 rue du Mulhouse,
BP 499, 90016 Belfort cedex, France.
Abstract OBJECTIVES: Post-partum anaemia is a very frequent condition affecting
4 to 27% of women who have given birth. Our study had the dual aim of
investigating daily clinical practice in dealing with severe anaemia of the
immediate post-partum period and of determining the place and efficacy of
treatment with intravenous iron: Venofer(R). PATIENTS AND METHODS: We conducted
a retrospective study in 4292 women who gave birth from April 2001 to March 2003
in the Department of Obstetrics and Gynaecology of Belfort Regional Hospital.
All patients who had a haemoglobin of less than 8 g/dL within 48 hours
post-partum (217 women or 5% of women who gave birth) were included and divided
into two groups depending on the availability or lack of availability of iron
treatment by the intravenous route at the time when they gave birth. A range of
clinical and laboratory parameters related to delivery were analysed. RESULTS:
The mean haemoglobin level in the 48 hours after delivery was: 5.81 g/dL for
transfused women; 6.88 g/dL for patients treated with intravenous iron and 7.43
g/dL for patients treated with oral iron. Fifteen patients were transfused in
the year prior to the introduction of treatment with intravenous iron and only
five the following year. A mean increase in haemoglobin of 1.9 g/dL within 7
days was obtained with intravenous iron and of 3.1 g/dL within 14 days without
any serious side effect. DISCUSSION AND CONCLUSION: These results suggest
efficacy of treatment with intravenous iron for severe post-partum anaemia with
entirely acceptable clinical tolerability. This treatment undoubtedly allows
some blood transfusions to be avoided in young women, even though the indication
for transfusion is unquestionable in the context of an emergency.
-----
Eur J Obstet Gynecol Reprod Biol. 2005 Dec;123 Suppl 2:S15-9.
Iron therapy in iron deficiency anemia in pregnancy: Intravenous
route versus oral route.
Bayoumeu F, Subiran-Buisset C, Baka NE, Legagneur H, Monnier-Barbarino P,
Laxenaire MC.
>From the Department of Anesthesia and Intensive Care, Maternity Hospital,
Supported by Maternity Hospital Nancy, France.
OBJECTIVE:: The aim of this study was to compare intravenous iron sucrose versus
oral iron sulfate in anemia at 6 months of pregnancy. STUDY DESIGN:: A random,
prospective, open study with individual benefit was performed involving 50
patients with hemoglobin levels between 8 and 10 g/dL and a ferritin value of
<50 mug/L. In the intravenous group (IV group), the iron dose was calculated
from the following formula: Weight before pregnancy (kg) x (120 g/L - Actual
hemoglobin [g/L]) x 0.24 + 500 mg. The oral group (PO group) received 240 mg of
iron sulfate per day for 4 weeks. Treatment efficacy was assessed by measurement
of hemoglobin and reticulocytes on days 8, 15, 21, and 30 and at delivery and of
ferritin on day 30 and at delivery. The baby's birth weight and iron stores were
noted. Results were expressed as median +/- intequartile range. Mann-Whitney and
Wilcoxon tests were used for the analysis, with P < .05 considered significant.
RESULTS:: An increase in hemoglobin was observed, rising from 9.6 +/- 0.79 g/dL
to 11.11 +/- 1.3 g/dL on day 30 in the IV group and from 9.7 +/- 0.5 g/dL to 11
+/- 1.25 g/dL on day 30 in the PO group (not significant). On day 30 (P < .0001)
and at delivery (P = .01) ferritin was higher in the IV group. A mean higher
birth weight of 250 g was noted in the IV group (not significant). CONCLUSION::
Iron sucrose appears to be a treatment without serious side effects indicated in
correction of pregnancy anemia or iron stores depletion. (Am J Obstet Gynecol
2002;186:518-22.).
-----
Nephrology (Carlton). 2005 Dec;10(6):583-7.
Melatonin corrects reticuloendothelial blockade and iron status
in haemodialysed patients.
Labonia W, Rubio D, Arias C.
Servicio de Nefrologia, Hospital Santojanni, Buenos Aires, Argentina.
SUMMARY: Aim: Treatment of anaemia in haemodialysed patients in the setting of
inflammation usually displays high levels of serum ferritin (>800 ng/mL) and low
transferrin saturation (TSAT) (<20%) despite i.v. iron supplementation, thus
proving iron trapping in the reticuloendothelial system. Melatonin has been
reported to reduce cytokine production and, in dialysis patients, to prevent
oxidative stress resulting from iron and erythropoietin treatment. Method: In
this study, we evaluated a group of 10 patients undergoing haemodialysis who
displayed elevated serum ferritin (981 +/- 44.6 ng/mL) and TSAT <20% (15.6 +/-
3.8%) after having received 1.2 g of i.v. iron dextran over a period of 8 weeks.
These patients received oral melatonin, 6 mg/day at night for 30 days. Results:
After this treatment, all of them markedly increased TSAT values, reaching 35.5
+/- 6.7% (P < 0.0001 vs basal values). In addition, ferritin values decreased to
754.4 +/- 263.7 ng/mL (P < 0.05), and serum iron dramatically increased in all
of the patients under study (42.4 +/- 9.4 vs 109.7 +/- 24.3 microg/dL; P <
0.0001). Values for haematocrit (28.6 +/- 2.7 vs 31.9 +/- 3.57%; P < 0.05) and
haemoglobin (9.19 +/- 0.97 vs 10.04 +/- 1.29 g/dL; P < 0.05) were also improved.
Measurements were then repeated 2 weeks after melatonin withdrawal, showing an
impressive decrease in TSAT (16.4 +/- 5.3%; P < 0.00001) and serum iron (48 +/-
14.7 microg/dL; P < 0.0001) values and an almost significant increase in
ferritin values (954.4 +/- 86 ng/mL; P < 0.054). Conclusion: The present study
demonstrates that melatonin may strongly correct the reticuloendothelial
blockade seen in dialysis patients under an inflammatory status, thus allowing a
better management of iron derangements and renal anaemia.
-----
Kidney Int Suppl. 2005 Dec;(99):S76-81.
Anemia management and chronic renal failure progression.
Rossert J, Froissart M, Jacquot C.
Paris-Descartes University School of Medicine, INSERM U652, AP-HP (Hopital
Europeen Georges Pompidou), Paris, France.
Anemia management and chronic renal failure progression. Analysis of the
biologic effects of erythropoietin and pathophysiology of chronic kidney
diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA)
could slow the progression of CKD. By decreasing hypoxia and oxidative stress,
it could prevent the development of interstitial fibrosis and the destruction of
tubular cells. It could have direct protective effects on tubular cells through
its antiapoptotic properties. It could help maintain the integrity of the
interstitial capillary network through its effects on endothelial cells. Thus,
suggesting that correcting anemia with ESA could slow the progression of CKD is
biologically plausible. In patients with CKD, three small prospective studies
and a retrospective study have suggested that treatment with ESA may have
protective effects. Post-hoc analysis of the Reduction in Endpoints in
Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist
Losartan study has also shown that anemia was an independent risk factor for
progression of nephropathy in patients with type 2 diabetes. In addition, a
large clinical trial, which had to be stopped prematurely because of labeling
change for subcutaneous administration of epoetin alfa, suggests that complete
normalization of hemoglobin levels is safe in CKD patients not on dialysis and
without severe cardiovascular disease. Thus, it seems reasonable to advocate
starting a large randomized, prospective study to determine if normalization of
hemoglobin concentration can effectively slow the progression of CKD.
-----
Ann Pharmacother. 2005 Dec 6; [Epub ahead of print]
Epoetin Alfa Versus Darbepoetin Alfa in Chemotherapy-Related
Anemia (CE) (January).
Cersosimo RJ, Jacobson DR.
Boston, MA.
OBJECTIVE: To review and compare the data concerning the clinical activity of
epoetin alfa versus darbepoetin alfa when administered to patients with cancer
who are experiencing treatment-related anemia. DATA SOURCES: English-language
publications from the MEDLINE database (1990-June 2005), published articles, and
meeting abstracts were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant
data were extracted from published reports and abstracts on studies of humans
with cancer who developed treatment-related anemia and were treated with epoetin
alfa or darbepoetin alfa. DATA SYNTHESIS: Epoetin alfa and darbepoetin alfa are
similar agents with identical indications for treatment of anemia in patients
with cancer. Clinical trials have demonstrated that both agents can
significantly improve hemoglobin levels, reduce transfusion requirements, and
improve quality of life. Epoetin alfa is approved for administration at a dose
of 150 units/kg subcutaneously 3 times per week, and darbepoetin alfa is
approved for administration at a dose of 2.25 units/kg once a week. Clinical
studies have demonstrated that epoetin alfa may be administered at 40 000 units
once a week and that darbepoetin alfa may be administered at 200 microg every 2
weeks without loss of efficacy. Cost analysis, based on the average wholesale
price of each drug alone administered for 12 weeks at Food and Drug
Administration-approved doses, revealed that epoetin alfa is less expensive than
darbepoetin alfa. When they are administered in the extended schedules, the cost
of darbepoetin alfa is slightly less than that of epoetin alfa. However, the
total expense associated with the extended schedule of either agent is further
reduced by a reduction in other costs associated with drug administration.
CONCLUSIONS: Epoetin alfa and darbepoetin alfa have identical indications for
treatment of anemia in patients receiving cancer chemotherapy. Clinical trials
have demonstrated similar activities with both agents. Darbepoetin alfa, with a
longer half-life, can be administered less frequently, saving costs as well as
reducing patient office visits. ((CE)) This article is approved for continuing
education credit ACPE UNIVERSAL PROGRAM NUMBER: 407-000-06-xxx-H01.
-----
Cancer. 2005 Dec 5; [Epub ahead of print]
Are there clinical benefits with early erythropoietic
intervention for chemotherapy-induced anemia?
Lyman GH, Glaspy J.
James P. Wilmot Cancer Center, University of Rochester School of Medicine and
Dentistry, Rochester, New York.
BACKGROUND: In recent years there has been an increasing debate regarding the
benefits of initiating erythropoietic treatment in patients with cancer when
anemia is still relatively mild. To address this, a systematic review of studies
was conducted that answered the following question: Is there a clinical benefit
associated with early erythropoietic intervention (hemoglobin >/= 10 g/dL) for
chemotherapy-induced anemia? METHODS: A systematic review of published
literature and meeting abstracts was undertaken to identify relevant studies.
Data were extracted from studies meeting prespecified eligibility criteria. For
outcome measures not associated with significant heterogeneity, summary measures
of relative risk associated with early erythropoietic intervention were
estimated using the method of Mantel and Haenszel. RESULTS: Eleven studies were
eligible and were included in the review. Erythropoietic treatment effectively
decreased transfusion incidence and the proportion of patients with hemoglobin <
10 g/dL compared with no treatment, with relative risk reductions of 0.50 (95%
confidence interval [CI], 0.43, 0.59; 7 studies, P < 0.0001) and 0.40 (95% CI,
0.19, 0.83; 4 studies, P = 0.147), respectively. The findings from both
prospective studies and planned subset analyses in which early and late
intervention were compared also indicated a reduction in the relative risk of
both transfusions and hemoglobin < 10 g/dL after early intervention (0.55 [95%
CI, 0.42, 0.73; 5 studies, P < 0.0001] and 0.44 [95% CI, 0.33, 0.57; 2 studies,
P < 0.0001], respectively). CONCLUSION: Collectively, these findings suggest
that optimal clinical benefit from erythropoietic treatment of
chemotherapy-induced anemia may be achieved through early intervention. Cancer
2006. (c) 2005 American Cancer Society.
-----
Nutr Hosp. 2005 Nov-Dec;20(6):433-5.
[Management, prevention and control of pernicious anemia]
[Article in Spanish]
De Paz R, Hernandez-Navarro F.
Servicio de Hematologia y Hemoterapia Hospital Universitario La Paz Madrid.
depazraquel@terra.es
Pernicious anemia is the most frequent cause of megaloblastic anemia in our
area, and it is the result of a vitamin B12 deficiency due, itself, to the
decrease or absence of intrinsic factor (IF) because of gastric mucosa atrophy
or autoimmune destruction of IF-producing parietal cells. With the existence of
a severe gastric atrophy, there is a decrease in acid and IF production and a
further change in vitamin B12 absorption. Fifty percent of the cases are
associated to anti-IF antibodies, which presence in other autoimmune diseases is
exceptional. In patients with pernicious anemia, measurement of anti-IF
antibodies has high specificity (95%); however, measurement of anti-parietal
cells antibodies has low specificity. The first-choice treatment is
administration of vitamin B12 intramuscularly. The regimen is the administration
of 1 mg of vitamin B12 daily for one week, weekly thereafter for one month and,
then, every 2-3 months for life.
-----
Ann N Y Acad Sci. 2005 Nov;1054:78-91.
Progress Toward the Genetic Treatment of the {beta}-Thalassemias.
Sadelain M, Lisowski L, Samakoglu S, Rivella S, May C, Riviere I.
Laboratory of Gene Transfer and Gene Expression, Memorial Sloan-Kettering Cancer
Center, Box 182, 1275 York Ave., New York, NY 10021. m-sadelain@ski.mskcc.org.
The beta-thalassemias are congenital anemias that are caused by mutations that
reduce or abolish expression of the beta-globin gene. They can be cured by
allogeneic hematopoietic stem cell (HSC) transplantation, but this therapeutic
option is not available to most patients. The transfer of a regulated beta-globin
gene in autologous HSCs is a highly attractive alternative treatment. This
strategy, which is simple in principle, raises major challenges in terms of
controlling expression of the globin transgene, which ideally should be
erythroid specific, differentiation- and stage-restricted, elevated, position
independent, and sustained over time. Using lentiviral vectors, May et al.
demonstrated in 2000 that an optimized combination of proximal and distal
transcriptional control elements permits lineage-specific and elevated beta-globin
expression, resulting in therapeutic hemoglobin production and correction of
anemia in beta-thalassemic mice. Several groups have by now replicated and
extended these findings to various mouse models of severe hemoglobinopathies,
thus fueling enthusiasm for a potential treatment of beta-thalassemia based on
globin gene transfer. Current investigation focuses on safety issues and the
need for improved vector production methodologies. The safe implementation of
stem cell-based gene therapy requires the prevention of the formation of
replication-competent viral genomes and minimization of the risk of insertional
oncogenesis. Importantly, globin vectors, in which transcriptional activity is
highly restricted, have a lesser risk of activating oncogenes in hematopoietic
progenitors than non-tissue-specific vectors, by virtue of their late-stage
erythroid specificity. As such, they provide a general paradigm for improving
vector safety in stem cell-based gene therapy.
-----
Am J Med. 2005 Oct;118(10):1154-9.
Food-cobalamin malabsorption in elderly patients: Clinical
manifestations and treatment.
Andres E, Affenberger S, Vinzio S, Kurtz JE, Noel E, Kaltenbach G, Maloisel F,
Schlienger JL, Blickle JF.
Department of Internal Medicine, Diabetes and Metabolic Disorders, Hopitaux
Universitaires de Strasbourg, Strasbourg, France.
PURPOSE: Approximately 15% of people aged more than 60 years old have a
cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin
malabsorption (FCM). To date, no study has documented this disorder in the
elderly. There is also little information on clinical consequences. SUBJECTS AND
METHODS: We studied 92 elderly patients with well-established FCM who were
extracted from an observational cohort study (1995-2004) of 172 consecutive
elderly patients with documented cobalamin deficiency. RESULTS: The median
patient age was 76 +/- 8 years; 60 patients were women. The most common clinical
manifestations were neurologic or psychologic: mild sensory polyneuropathy
(44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia
(20.7%). Hematologic abnormalities were reported in at least one third of the
patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and
pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL),
with a mean value (+/- standard deviation) of 131 +/- 38 pg/mL and total serum
homocysteine level of 22.1 +/- 9.3 mumol/L. The mean hemoglobin level was 10.9
+/- 2.5 g/dL and the mean erythrocyte cell volume 95.7 +/- 12.7 fL. Correction
of the serum vitamin B12 levels and hematologic abnormalities was achieved
equally well in patients treated with either intramuscular or oral crystalline
cyanocobalamin. CONCLUSIONS: This study suggests that in elderly patients, FCM
may be associated with significant neurologic, psychologic, and hematologic
abnormalities, which seem to respond equally well to either oral or parenteral
vitamin B12 therapy.
-----
Am J Med. 2005 Oct;118(10):1142-7.
Are we giving too much iron? Low-dose iron therapy is effective
in octogenarians.
Rimon E, Kagansky N, Kagansky M, Mechnick L, Mashiah T, Namir M, Levy S.
Geriatrifc Department, Kaplan Medical Center, Rehovot, and the Hebrew University
and Hadassah Medical School, Jerusalem, Israel.
PURPOSE: Elderly patients are vulnerable to the dose-dependent adverse effects
of iron replacement therapy. Our study examines whether low-dose iron therapy
can efficiently resolve iron-deficiency anemia in patients over the age of 80
years and reduce adverse effects. SUBJECTS AND METHODS: Ninety hospitalized
patients with iron-deficiency anemia were randomized to receive elemental iron
in daily doses of 15 mg or 50 mg as liquid ferrous gluconate or 150 mg of
ferrous calcium citrate tablets for 60 days. Thirty control patients without
anemia were given 15 mg of iron for 60 days. A 2-hour iron absorption test was
performed after the initial dose. Hemoglobin and ferritin levels were measured
on day 1, 30, and 60 after initiating therapy. Each patient completed a weekly
questionnaire regarding drug-induced adverse effects. RESULTS: Serum iron rose
significantly in the anemic patients beginning 15 minutes after the first dose
but not in nonanemic patients. Two months of iron treatment significantly
increased hemoglobin and ferritin concentrations similarly in all 3 groups of
iron-deficiency anemia patients (for example, hemoglobin levels rose from 10.0
g/dL to 11.3 g/dL with 15 mg/d of iron therapy and from 10.2 g/dL to 11.6 g/dL
with 150 mg/d). Abdominal discomfort, nausea, vomiting, changes in bowel
movements, and black stools were significantly more common at higher iron doses.
CONCLUSIONS: Low-dose iron treatment is effective in elderly patients with
iron-deficiency anemia. It can replace the commonly used higher doses and can
significantly reduce adverse effects.
-----
J Clin Oncol. 2005 Oct 1;23(28):6941-8.
Darbepoetin alfa for the treatment of chemotherapy-induced
anemia: disease progression and survival analysis from four randomized,
double-blind, placebo-controlled trials.
Hedenus M, Vansteenkiste J, Kotasek D, Austin M, Amado RG.
Department of Internal Medicine, Sundsvall Hospital, Sundsvall S-851 86, Sweden;
e-mail: Michael.Hedenus@lvn.se.
PURPOSE To determine the effect of darbepoetin alfa (DA) on progression-free
survival (PFS) and overall survival (OS) in patients with chemotherapy-induced
anemia (CIA). PATIENTS AND METHODS Two 16-week randomized, double-blind,
placebo-controlled phase III studies of weekly DA in anemic patients with lung
cancer (n = 314) or lymphoproliferative malignancies (LPMs; n = 344) undergoing
chemotherapy were analyzed with prospectively defined long-term PFS and OS end
points. Short-term effects of DA on PFS and OS were analyzed by including two
additional 16-week dose-finding, double-blind, placebo-controlled studies in
anemic patients with multiple tumor types (n = 405) and LPMs (n = 66). Results
Median follow-up is 15.8 months (lung cancer) and 32.6 months (LPM). Median
duration of PFS was comparable between DA and placebo: 5.1 months (95% CI, 4.1
to 6.9 months) versus 4.4 months (95% CI, 3.7 to 5.3 months) for lung cancer and
14.2 months (95% CI, 12.2 to 17.5 months) versus 15.9 months (95% CI, 13.1 to
19.0 months) for LPMs. The estimated hazard ratio (HR) of death related to DA
use for lung cancer was 0.77 (95% CI, 0.59 to 1.01) and 1.26 (95% CI, 0.92 to
1.71) for LPMs. In the pooled analyses of all four studies (n = 1,129), no
differences in PFS or OS were observed between DA and placebo (HR = 0.92; 95%
CI, 0.78 to 1.07; and HR = 0.95; 95% CI, 0.78 to 1.16, respectively). CONCLUSION
Treatment with DA does not seem to influence PFS or OS in patients with CIA.
Prospective, randomized clinical trials will provide additional insights into
the effects of DA on PFS and OS in specific tumor types.
-----
Blood. 2005 Oct 1;106(7):2269-75.
Long-term hydroxyurea therapy for infants with sickle cell
anemia: the HUSOFT extension study.
Hankins JS, Ware RE, Rogers ZR, Wynn LW, Lane PA, Scott JP, Wang WC.
St Jude Comprehensive Sickle Cell Center, Department of Hematology-Oncology, St
Jude Children's Research Hospital, 332 N Lauderdale, MS 763, Memphis TN 38105.
jane.hankins@stjude.org.
The long-term efficacy and toxicity of hydroxyurea for infants are undefined,
and its role in preventing organ dysfunction is unknown. Short-term feasibility
of hydroxyurea administration, toxicities, hematologic effects, and effect on
spleen function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea
Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of
hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose
escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and
biannual imaging studies. Hematologic indices were compared with predicted
age-specific values and event rates compared with historic rates. All 21
subjects completing the original trial enrolled in the extension study: median
age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with
Hb S/beta(0)-thalassemia. Seventeen patients completed 4 years of hydroxyurea,
and 11 completed 6 years. After 4 years, hydroxyurea was associated with
increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and
mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs),
and platelets (P < .01). Patients experienced 7.5 acute chest syndrome (ACS)
events per 100 person-years, compared with 24.5 events per 100 person-years
among historic controls (P = .001). Treated patients had better spleen function
than expected and improved growth rates. Infants with SCA tolerate prolonged
hydroxyurea therapy with sustained hematologic benefits, fewer ACS events,
improved growth, and possibly preserved organ function.
-----
Ann Pharmacother. 2005 Sep 27; [Epub ahead of print]
Darbepoetin Alfa Therapeutic Interchange Protocol for Anemia in
Dialysis (November).
Brophy DF, Ripley EB, Kockler DR, Lee S, Proeschel LA.
School of Pharmacy, Virginia Commonwealth University/Medical College of Virginia
(VCU/MCV), Richmond, VA.
BACKGROUND: Erythropoiesis-stimulating proteins, such as erythropoietin alfa and
darbepoetin alfa, have positively impacted anemia management. These medications
improve patient outcomes and quality of life. Their costs, however, remain a
major barrier for health systems. OBJECTIVE: To evaluate the development,
implementation, and cost-effectiveness of an inpatient therapeutic interchange
protocol for erythropoiesis-stimulating proteins at a large, tertiary care,
university-affiliated health system. METHODS: Virginia Commonwealth University
Health System (VCUHS) developed and implemented a therapeutic interchange
program to convert therapy for all inpatients undergoing dialysis from
erythropoietin alfa to darbepoetin alfa for treatment of chronic kidney
disease-related anemia. An evaluation of the economic impact of this program on
drug expenditures over a fiscal quarter (2003) was conducted using historical
comparator data (2002). RESULTS: Preliminary evaluation of the program
demonstrated cost-savings and reduced drug utilization of erythropoiesis-stimulating
proteins in hospitalized dialysis patients. For the first quarter of 2003
compared with the first quarter of 2002, VCUHS realized a cost-savings of nearly
$10 000, which was related to the program's aggressive screening procedure. When
these data were normalized for equal numbers of patients in each group receiving
one of the drugs, the actual cost-savings was over $2000. These cost-savings are
largely due to reduced utilization of these expensive biotechnology products
with implementation of a dosing protocol. CONCLUSIONS: VCUHS has successfully
developed and implemented a darbepoetin alfa therapeutic interchange protocol
for hospitalized dialysis patients. This has translated into reduced use of
erythropoiesis-stimulating proteins, resulting in cost-savings for the health
system.
-----
Transfus Clin Biol. 2005 Sep 14; [Epub ahead of print]
[Blood product transfusion in the neonatal period.]
[Article in French]
Arnaud F, Simeoni U.
Service de neonatalogie, faculte de medecine, universite de la Mediterranee,
hopital de La Conception, AP-HM, 147, boulevard Baille, 13385 Marseille cedex
France.
Newborn infants in intensive care units, especially those born premature, are at
particular risk for blood transfusion adverse effects. Aside improvements in the
preparation of specific blood products for the neonatal period, such as multiple
packed cells preparations from a single donor for multiple transfusions in
premature infants, progress has involved prophylaxis of anemia of prematurity as
well. Recombinant human erythropoietin has proven to be beneficial with high
range evidence. Also, alternative methods have been proposed to compensate for
the delay in the effect of rHuEPO, such as delayed clamping of umbilical cord at
birth, or autologous placental blood transfusion. However, a better
understanding of the indications of blood transfusion and the provision of
practice guidelines may justify a re-evaluation of prophylactic strategies for
anemia of prematurity.
-----
Ann Oncol. 2005 Sep 15; [Epub ahead of print]
Darbepoetin alfa for the treatment of anemic patients with low-
and intermediate-1-risk myelodysplastic syndromes.
Stasi R, Abruzzese E, Lanzetta G, Terzoli E, Amadori S.
Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale,
Italy.
BACKGROUND: The hematological and quality of life (QoL) changes associated with
darbepoetin alfa (DA) therapy were assessed in anemic patients with previously
untreated low- and intermediate-1-risk myelodysplastic syndrome (MDS). PATIENTS
AND METHODS: Fifty-three patients received DA administered subcutaneously once a
week for 24 weeks. Treatment was initiated at 150 microg fixed dose and was
doubled if after the first 12 weeks there was no or suboptimal erythroid
response. RESULTS: The final response rate was 24/53 (45%), with 21 major and
three minor responses. Most of the responses (21/24; 87.5%) were obtained at the
dose of 150 microg. With a median follow-up of 9.4 months, 17 patients maintain
their response. Treatment was well tolerated with no relevant side-effects. MDS
progression was observed in one case. Increases in hemoglobin levels were
positively correlated with improved QoL scores using both the linear analog
scale assessment (energy level, r = 0.429, P = 0.036; daily activities, r =
0.653, P < 0.001; overall well-being, r = 0.457, P = 0.024) and the Functional
Assessment of Cancer Therapy-Anemia questionnaire (r = 0.247, P = 0.025). In
multivariate analysis, only low levels (<200 IU/l) of endogenous erythropoietin
predicted response to DA therapy. CONCLUSIONS: DA is an active, safe and well
tolerated treatment for anemia in a substantial proportion of patients with low-
and intermediate-1-risk MDS, and has a positive impact on the patients' QoL.
-----
Transplant Proc. 2005 Jul-Aug;37(6):2667-9.
Allogeneic stem cell transplantation.
Bosi A, Bartolozzi B, Guidi S.
BMT Unit, Department of Hematology, University of Florence, Florence, Italy.
Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate
number of stem cells (SC) from a histocompatible donor and their infusion into a
patient following a conditioning regimen. During the past 35 years, the role of
HSCT has changed from an experimental procedure for terminally ill patients to a
curative treatment. In 2003, 1170 procedures were registered in Italy (Italian
Group for Blood and Marrow Transplantation). The main reported indications were
as follows: leukemia, lymphoproliferative diseases, myelodysplasia, and
nonmalignant diseases such as thalassemia and severe aplastic anemia. Important
changes have been observed in the last 5 years: the shift from bone marrow to
peripheral blood as the SC source, the increasing number of alternative donors
such as unrelated, partially matched family donors and cord blood SC, and the
new extra-hematological indications including solid tumors. Moreover, the
development of nonmyeloablative conditionig regimens have allowed physicians to
perform HSCT in patients with advanced age or important comorbidities. In
contrast, the availability of the Tyrosine kinase inhibitor (STI-571) for
treatment of patients affected by chronic myelogenous leukemia, which was
formerly the main indication for HSCT, has produced a dramatic decrease in the
number of transplantations in this setting. HSCT performed in the early phases
of disease and in young patients offers more than a 50% cure rate. The
transplant-related mortality still represents the greatest obstacle, ranging
from 20%-30%, despite the less toxic conditioning regimens, high-resolution HLA
typing, and better supportive care. GvHD and infections remain the main causes
of morbidity. As regards relapses, they correlate with disease status at the
time of transplantation. Promising results have been recently obtained with
haploidentical and with cord blood SC transplantation also in adult patients.
-----
J Cardiovasc Pharmacol. 2005 Aug;46(2):155-161.
Once-Monthly Administration of Darbepoetin Alfa for the Treatment
of Patients with Chronic Heart Failure and Anemia: A Pharmacokinetic and
Pharmacodynamic Investigation.
Cleland JG, Sullivan JT, Ball S, Horowitz JD, Agoram B, Rosser D, Yates W, Tin
L, Fuentealba P, Burton PB.
>From the *Department of Cardiology, University of Hull, Castle Hill Hospital,
Kingston upon Hull, UK; daggerAmgen Inc, Thousand Oaks, California; double
daggerAcademic Unit of Cardiovascular Medicine, Yorkshire Heart Centre, Leeds,
UK; and section signThe Queen Elizabeth Hospital, University of Adelaide,
Adelaide, Australia.
In patients with chronic heart failure (CHF), anemia is associated with more
severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs)
increase hemoglobin and may be of therapeutic benefit. We investigated the
pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa,
administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients
with symptomatic CHF and anemia (hemoglobin </=12.5 g/dL) in 2 randomized,
double-blind, placebo-controlled studies. Subcutaneous (SC) and intravenous
administration of 0.75 mug/kg of darbepoetin alfa were compared in a crossover
study. The second study compared 2.0, 3.0, and 5.0 mug/kg SC doses with placebo.
Darbepoetin alfa (0.75 mug/kg SC) pharmacokinetics were similar in CHF patients
and healthy subjects, with a mean (+/-SD) bioavailability of 29 (+/-11)% and 37
(+/-8)%, respectively. In anemic CHF patients, mean (+/-SD) increases in
hemoglobin at 4 weeks after the second monthly dose of 2.0, 3.0, and 5.0 mug/kg
(SC) of darbepoetin alfa were 2.3 (+/-0.6), 1.4 (+/-1.0), and 2.4 (+/-1.9) g/dL,
respectively. Darbepoetin alfa 0.75 mug/kg (SC) given twice, 1 month apart, was
insufficient to increase hemoglobin in this study. No severe, drug-related
adverse events occurred. Darbepoetin alfa administered once monthly elevates and
maintains the hemoglobin concentration in patients with CHF and anemia.
-----
Biol Blood Marrow Transplant. 2005 Aug;11(8):600-8.
Bone marrow transplantation for diamond-blackfan anemia.
Roy V, Perez WS, Eapen M, Marsh JC, Pasquini M, Pasquini R, Mustafa MM, Bredeson
CN.
Abstract Patients with Diamond-Blackfan anemia (DBA) who are unresponsive to or
intolerant of corticosteroids, experience treatment failure with other
treatments, develop additional cytopenias or clonal disease, or opt for curative
therapy are often treated with allogeneic bone marrow transplantation. We
studied the transplantation outcomes of 61 DBA patients whose data were reported
to the International Bone Marrow Transplant Registry between 1984 and 2000. The
median age was 7 years (range, 1-32 years). Among 55 patients with available
transfusion information, 35 (64%) had received >/=20 units of blood before
transplantation. Most patients (67%) received their bone marrow grafts from an
HLA-matched related donor. The median time to neutrophil recovery was 17 days
(range, 10-119 days) and to platelet recovery was 23 days (range, 9-119 days).
Five patients did not achieve neutrophil engraftment. The 100-day mortality was
18% (95% confidence interval, 10%-29%). Grade II to IV acute graft-versus-host
disease occurred in 28% (range, 17%-39%) and chronic graft-versus-host disease
in 26% (range, 15%-39%). The 3-year probability of overall survival was 64%
(range, 50%-74%). In univariate analysis, a Karnofsky score >/=90 and
transplantation from an HLA-identical sibling donor were associated with better
survival. These data suggest that allogeneic bone marrow transplantation is
effective for the treatment of DBA. Transplantation before deterioration of the
performance status and from an HLA-identical sibling donor may improve survival.
-----
Semin Hematol. 2005 Jul;42(3):131-6.
Treatment of autoimmune hemolytic anemia.
King KE, Ness PM.
The appropriate therapy of autoimmune hemolytic anemia (AIHA) is dependent on
the correct diagnosis and classification of this family of hemolytic disorders.
Although the majority of cases are warm AIHA, there are several distinct types
of cold AIHA and a number of drug-induced etiologies of AIHA, which must be
investigated to determine if stopping a drug will induce a remission. In warm
AIHA, corticosteroids are standard, followed by consideration of splenectomy in
recalcitrant cases. If steroids and splenectomy are insufficient, other forms of
immunosuppressive therapy are typically initiated. In cold AIHA, keeping the
patient warm in often sufficient, but therapy directed at an underlying
lympholiferative disorder may be helpful. Brisk hemolysis, inadequate responses
to therapy, and worsening anemia require transfusion therapy. Although the
pretransfusion workup is made difficult by the presence of the autoantibody,
transfusion services can usually provide blood safe for transfusion by excluding
underlying alloantibodies. When transfusion is urgently required and compatible
blood cannot be located, incompatible blood may be provided as a life-saving
measure. Communication between the transfusion service and the hematologist is
critical to assess the risks in these settings. Hemoglobin-based oxygen carriers
may provide an important bridging therapy in the future. Requests for "least
incompatible" blood do not enhance transfusion safety and often result in
unnecessary delays.
-----
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003266.
Recombinant human erythropoietin for chronic renal failure
anaemia in pre-dialysis patients.
Cody J, Daly C, Campbell M, Donaldson C, Khan I, Rabindranath K, Vale L, Wallace
S, Macleod A.
Cochrane Incontinence Review Group, University of Aberdeen, Health Services
Research Unit, Polwarth Building, Foresterhill, Aberdeen, UK, AB25 2ZD.
BACKGROUND: Treatment with recombinant human erythropoietin (rHu EPO) in
dialysis patients has been shown to be highly effective in terms of correcting
anaemia and improving quality of life. There is debate concerning the benefits
of rHu EPO use in pre-dialysis patients which may accelerate the deterioration
of renal function. However the opposing view is that if rHu EPO is as effective
in pre-dialysis patient's, improving the patients sense of well-being may result
in the onset of dialysis being delayed. OBJECTIVES: To assess the effects of rHu
EPO use in pre-dialysis patients with renal anaemia. SEARCH STRATEGY: The
initial search included 13 electronic databases (1980 to May 2001) an internet
search (August 1997), handsearching of Kidney International (1983 to May 1997),
contact with known investigators and biomedical companies, and reference list of
relevant articles. For this update we searched the Cochrane Renal Group's
specialised register (June 2004) and The Cochrane Library (Issue 3, 2004).
SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing
the use of rHu EPO with no treatment or placebo in pre-dialysis patients. DATA
COLLECTION AND ANALYSIS: Only published data were used. Quality assessment was
performed by two assessors independently. Data were abstracted by a single
author onto a standard form, a sample of which was checked by another author.
Results were expressed as relative risk (RR) or weighted mean difference (WMD)
with 95% confidence intervals (CI). MAIN RESULTS: Fifteen trials (461
participants) were included. There was a marked improvement in haemoglobin (WMD
1.82 g/dL, 95% CI 1.35 to 2.28) and haematocrit (WMD 9.85%, 95% CI 8.35 to
11.34) with treatment and a decrease in the number of patients requiring blood
transfusions (RR 0.32, 95% CI 0.12 to 0.83). The data from studies reporting
quality of life or exercise capacity demonstrated an improvement in the
treatment group. Most of the measures of progression of renal disease showed no
statistically significant difference. No significant increase in adverse events
was identified. AUTHORS' CONCLUSIONS: Treatment with rHu EPO in pre-dialysis
patients corrects anaemia, avoids the requirement for blood transfusions and
also improves quality of life and exercise capacity. We were unable to assess
the effects of rHu EPO on progression of renal disease, delay in the onset of
dialysis or adverse events. Based on the current evidence, decisions on the
putative benefits in terms of quality of life are worth the extra costs of
pre-dialysis rHu EPO need careful evaluation.
-----
Nephrol Dial Transplant. 2005 Jul;20 Suppl 7:vii7-vii10.
Anaemia and heart failure: aetiology and treatment.
Klutstein MW, Tzivoni D.
Director, Department of Cardiology, Shaare Zedek Medical Center, 12 Hans Beyth
Street, POB 3235, Jerusalem 91031, Israel. cardio@szmc.org.il.
Heart failure (HF) is a common disease associated with poor prognosis. Anaemia
is commonly associated with HF due to bone marrow depression, reduced
availability of iron and haemodilution, and is sometimes aggravated by too
frequent blood testing. Low haemoglobin is very detrimental to the haemodynamic
state of the patient with decreased cardiac output as it further diminishes the
oxygen supply to the tissues. When anaemia is associated with HF. and renal
failure, the patient enters a vicious cycle called cardio renal anaemia
syndrome. The prognosis of patients with HF is worse as the haemoglobin is lower
and even mild anaemia is associated with <1 year survival. Aggressive correction
of the anaemia by subcutaneous injections of erythropoeitin and intravenous iron
has been shown to improve the functional capacity and quality of life of
patients with cardio renal anaemia syndrome and to reduce the need for
hospitalization. However, intravenous iron can be detrimental because of
increased formation of free radicals, oxidative stress and risk of infection.
The level of haemoglobin needed to be achieved is not clear, but it seems
indicated to maintain it above 12 g%.
-----
Nephrol Dial Transplant. 2005 Jul;20 Suppl 7:vii16-vii23.
Intravenous iron supplementation in the anaemia of renal and
cardiac failure--a double-edged sword?
Slotki I.
Division of Adult Nephrology, Shaare Zedek Medical Center, PO Box 3235,
Jerusalem, 91031 Israel. islotki@szmc.org.il.
The anaemia of chronic kidney disease (CKD) is efficiently corrected with a
combination of recombinant erythropoietin (rhEPO) and intravenous iron
supplementation. Recently, patients with severe cardiac failure and anaemia have
also been shown to benefit from this treatment. However, iron excess may lead to
the production of free radicals and has been incriminated in the pathogenesis of
atherosclerosis and increased risk of infection, the two major causes of death
in end-stage renal disease. The exact risk of excess iron supplementation has
not been defined and, in the absence of sensitive and specific indicators of
iron overload, the risk remains difficult to quantify. There is increasing
epidemiological evidence incriminating iron overload as a risk factor in CKD,
but direct evidence is still hard to obtain. The precise role of iron is
complicated further by the complex inter-relationships between iron metabolism
and the inflammatory process characteristic of CKD. The recent discovery of the
antimicrobial peptide, hepcidin, may shed light on these inter-relationships.
New methods for quantifying non-transferrin-bound (or labile plasma) iron may
help in the future to identify patients at risk for toxicity from excess iron
supplementation.
-----
Oncology. 2005 Jul 7;68(2-3):122-129 [Epub ahead of print]
Once-Weekly Treatment of Anemia in Patients with Cancer: A
Comparative Review of Epoetins.
Pujade-Lauraine E, Topham C.
Service d'Oncology, CHU Hotel Dieu, Paris, France.
Anemia is common in cancer patients, but its impact is often poorly appreciated.
As well as the negative effect of anemia on the quality of life, there is strong
evidence that it is associated with poor treatment outcome and reduced survival.
The introduction of recombinant human erythropoietin (epoetin) has provided an
effective treatment of anemia, without the risk associated with blood
transfusion. A recent randomized study of patients with hematological
malignancies showed that once-weekly epoetin beta has comparable efficacy at the
same overall weekly dose as three-times-weekly treatment. This once-weekly
regimen of epoetin beta (NeoRecormon((R))) has been approved by European
Regulatory Authorities for patients with lymphoproliferative malignancies and
relative erythropoietin deficiency, who are receiving anti-tumor therapy.
Darbepoetin alpha (Aranesp((R))) has also recently been approved for once-weekly
treatment of anemia in patients with nonmyeloid malignancies receiving
chemotherapy. The improved convenience and reduced administration costs
associated with a once-weekly treatment may result in more patients receiving
the benefits of epoetin therapy. Copyright (c) 2005 S. Karger AG, Basel.
-----
Anticancer Drugs. 2005 Jul;16(6):617-20.
Darbepoetin alpha as treatment for anemia in patients receiving
chemotherapy: a single-center experience.
Bartsch R, Wenzel C, Sevelda U, Hussian D, Pluschnig U, Locker GJ, Mader R,
Zielinski CC, Steger GG.
aDepartment of Internal Medicine I, Division of Oncology bChair of Medical
Oncology cLudwig Boltzmann Institute for Clinical Oncology, Medical University
of Vienna, Vienna, Austria.
We evaluated Darbepoetin alpha (Aranesp; Amgen), a novel erythropoietic protein,
in patients who developed anemia while receiving chemotherapy. Seventy-five
patients (median age 62 years, range 40-81 years) undergoing different cancer
chemotherapy regimens were treated with darbepoetin alpha. Therapy was started
if hemoglobin (Hb) levels fell below 10 g/dl or if symptomatic anemia developed.
Treatment effect was evaluated after 4 weeks, 8 weeks and at the end of therapy
(up to 12 weeks). If no increase in Hb was seen after 4 weeks, the dose of
darbepoetin alpha was increased to 300 mug. Patients were questioned about
fatigue and any change during treatment, with evaluation according to a
four-point scale, where 0=no fatigue and 3=severe fatigue. We observed a
treatment response in 54 of 75 patients (72%). Dose escalation was necessary in
30 of 75 patients (40%) and blood transfusions were required in 13 of 75
patients (17.3%). Response was observed in 32 of 43 patients (74.4%) who had a
baseline Hb<10 g/dl and in 22 of 32 (68.8%) patients who had a baseline Hb>/=10
g/dl. At baseline, 60 of 75 patients (93.3%) reported fatigue of grade 2 or 3,
but at the end of the 12-week follow-up period, only 26 of 68 patients (38.3%)
reported fatigue at these levels. We conclude that darbepoetin alpha is a highly
effective and well-tolerated drug in the treatment of chemotherapy-associated
anemia. Patients benefited both in terms of Hb levels and control of
chemotherapy-related symptoms.
-----
Pharmacotherapy. 2005 Jun;25(6):862-75.
Epoetin alfa for the Treatment of Combination Therapy-Induced
Hemolytic Anemia in Patients Infected with Hepatitis C Virus.
Rivkin AM, Chawla S.
Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island
University, Brooklyn, New York; Department of Pharmacy, St. Luke's-Roosevelt
Hospital Center, New York, New York.
In the United States, about 2.7 million people are chronically infected with the
hepatitis C virus, accounting for nearly 1.8% of the population. The current
standard of therapy is a combination of pegylated interferon products and
ribavirin. A common adverse effect associated with this therapy is anemia, which
is frequently referred to as mixed anemia because of the synergistic
contribution of the interferons and ribavirin. The effect of ribavirin on the
development of anemia is considered greater than that of interferon. The current
standard of practice for treating this adverse effect is reduction of the
dosages of both drugs, at prespecified hemoglobin levels. However, recent
findings underscore the importance of maintaining adequate dosages of interferon
and ribavirin, which may be crucial in achieving an early virologic response and
a sustained virologic response in treating patients with hepatitis C infection.
Treatment with epoetin alfa for this mixed anemia significantly improved
hemoglobin levels and quality of life, and enabled adequate dosages of ribavirin
to be maintained. Future studies should address several issues: when to start
epoetin alfa treatment, the duration of treatment, the drug's optimal dosage,
its effects on end-of-treatment and sustained virologic response rates, and a
cost analyses.
-----
Expert Opin Pharmacother. 2005 May;6(5):723-34.
Erythropoietin: an update on the therapeutic use in newborn
infants and children.
Donato H.
Department of Neonatology, Sanatorio de la Trinidad, Buenos Aires, Argentina.
hugodonato@aol.com
Recombinant human erythropoietin (epoetin) has become the most widely used
cytokine in the world. Following the success of its use in patients with
end-stage renal disease, the usefulness of epoetin in other anaemias was
assessed, including paediatric patients, mainly newborns. The treatment or
prevention of anaemia of prematurity with epoetin resulted in a significant
reduction in the number of transfusions and donor exposure. A clear definition
of which premature babies must receive therapy is yet to be established. Other
indications in neonatal period include hyporegenerative and haemolytic anaemias.
The potential for use of the nonhaematopoietic effects of epoetin in newborn
infants is a novel and exciting issue. The role of epoetin as a
tissue-protective factor for the CNS and intestinal mucosa is under exhaustive
investigation. With the exception of chronic renal failure, in older children
the efficacy of epoetin has not been evaluated as in adults. Although an
impressive amount of studies were carried out during recent years in adult
patients with cancer-related or HIV-infection-related anaemias, thus allowing
clear conclusions to be established on its efficacy, only a few trials with a
small number of patients have been reported in children. Up-to-date, results in
paediatric patients suggest that epoetin therapy is as useful as in adult
patients, but prospective, randomised trials including large number of patients
are essential to achieve definitive conclusions.
-----
Expert Opin Biol Ther. 2005 May;5(5):617-26.
Haematopoietic stem cell transplantation to treat aplastic
anaemia.
Jaime-Perez JC, Ruiz-Arguelles GJ, Gomez-Almaguer D.
Universidad Autonoma de Nuevo Leon Servicio de Hematologia, Hospital
Universitario, Dr Jose E. Gonzalez, Edificio Dr Rodrigo Barragan, 2 piso.,
Avenida Madero y Gonzalitos, Monterrey, Nuevo Leon, C.P. 64460, Mexico. carjaime@hotmail.com
Aplastic anaemia (AA) consists of pancytopenia and empty bone marrow. Its
incidence varies worldwide but predominates in developing countries. Diverse
aetiologies are involved, with autoimmunity at the centre of the picture. For
the 70% of patients with the severe and very severe forms of AA and who lack a
human leukocyte antigen (HLA)-matched sibling, immunosuppressive therapy (IST)
is key in treating the disease, with a remission rate close to 70%, an 80-90%
5-year survival rate in responding patients and a relapse rate close to 10%. For
the 30% with a sibling donor available, haematopoietic stem cell transplant (HSCT)
from bone marrow or peripheral blood has up to a 90% chance of cure, with a
5-10% graft rejection/failure rate. Patients who fail IST (25-30%) and lack a
sibling donor can benefit from CD34(+)-enriched, partially T cell-depleted
unrelated stem cell transplants, with a general survival rate up to 37%, the
newest source of stem cells for this modality being cord blood. Non-myeloablative,
irradiation-free conditioning regimens offer appreciable benefits, and new
immunosuppressive agents, such as fludarabine and alemtuzumab, have been
incorporated with promising preliminary results. Graft-versus-host disease,
graft failure and infections remain significant challenges in HSCT for which
innovative treatment strategies are being developed at present.
-----
Bull Cancer. 2005 May 1;92(5):439-44.
[Anemia in lung cancer patients]
[Article in French]
Meric JB, Morere JF; CLub de l'ANemie.
Service d'Oncologie Medicale, Hopital Pitie-Salpetriere, 43-87 bd de l'Hopital,
75013 Paris. jean-baptiste.meric@libertysurf.fr
Anemia and fatigue are frequent in lung cancer patients. Anemia is due to cancer
and platinum-based chemotherapy. Anemia leads to a wide range of symptoms and
affects health-related quality of life. Anemia also worsens outcome of therapy
and prognosis. Efficient treatment exist: blood transfusion and recombinant
erythropoietin. Early treatment of anemia is recommended as soon as diagnosis is
made. But few patients receive optimal treatment. Its cost and unsolved question
regarding therapeutic strategies may explain this phenomenon. This debate should
not preclude correct treatment prescription. Clinical trials have to be
preformed to clarify unsolved questions. As EPO administration can affect
survival, this point should be of particular interest in future trials.
-----
Bull Cancer. 2005 May 1;92(5):445-51.
[Anemia in head and neck cancers]
[Article in French]
Azria D, Zouhair A, Serre A, Lemanski C, Schneider M, Ozsahin M, Dubois JB,
Lartigau E; Club de Lutte Contre l'Anemie.
Departement d'Oncologie-Radiotherapie, EMI0227, CRLC Val d'Aurelle-Paul Lamarque,
Rue Croix Verte, 34298 Montpellier Cedex. azria@valdorel.fnclcc.fr
Anemia is very common in head and neck cancer patients, and seems to be
correlated with intratumoral hypoxia. Anemia is one of the main prognostic
factors of locoregional recurrence and, in some studies, of poor survival. Blood
transfusions and human recombinant erythropoietin (rHuEPO) are the two main
methods used in clinical practice to correct hemoglobin level during curative
treatment. Blood transfusions were rarely evaluated, and did not influence
locoregional control of patients treated with radiotherapy with or without
chemotherapy. Retrospective studies evaluating combined treatment of rHuEPO and
radiotherapy reported positive impact on locoregional recurrence and actuarial
survival. Since the end of 2003, this approach is a matter for debate after the
negative results of a prospective randomized study on progression-free survival
concerning head and neck cancer patients treated with definitive or
postoperative external radiotherapy with or without rHuEPO. Although many biases
were reported against this publication, several questions are to be answered in
the near future. Among them, erythropoietin receptor expression and activation
on tumour cell seem to be the more appropriate explanation of these negative
results. In October 2004, preliminary results of the RTOG 99-03 study have been
presented at the Astro annual meeting in Atlanta. This prospective randomized
trial was designed to determine if concurrent rHuEPO administration (40,000
units) with radiotherapy (with or without chemotherapy) could improve
locoregional control in non-operative head and neck cancers. In the rHuEPO arm,
haemoglobin level was significantly increased compared with control arm.
However, the addition of concurrent rHuEPO to definitive radiotherapy did not
improve locoregional control or survival for mildly/moderately anemic patients
with head and neck squamous cell carcinoma. Future clinical trials using
biological markers are thus imperative to target which patients could benefit
from these molecules.
-----
Bull Cancer. 2005 May 1;92(5):432-8.
[Anemia and colorectal cancer]
[Article in French]
Vignot S, Spano JP; CLub ANemie.
Service d'Oncologie Medicale, Hopital Saint-Louis, 1 avenue Claude-Vellefaux,
75010 Paris. stephanevignot@slsap-hop-paris-fr
Colorectal cancers are classically revealed by a low digestive bleeding, which
can be occult or exteriorized. They commonly present anemia at the diagnosis
leading to particular outcomes. Perioperative blood transfusions are frequently
indicated for the treatment of localized tumors and for hepatic resection of
metastatic lesions but transfusions seem to have a negative impact on prognosis
by increasing infections and potentially recurrence. In this context, various
strategies aim at limiting the transfusional risk (autologous transfusion,
preoperative use of erythropoietin...). Anemia associated with advanced
colorectal cancers provides the same interest as for any metastatic tumor, as
quality of life of patients is correlated to the hemoglobin's level.
-----
Minerva Urol Nefrol. 2005 Mar;57(1):23-31.
Anemia and erythropoietin treatment in chronic kidney diseases.
Santoro A, Canova C.
Unit of Nephrology and Dialysis, Policlinico S.Orsola-Malpighi, Bologna, Italy.
In patients with renal failure, severe anemia and associated fatigue, cognitive
and sexual dysfunctions have a significant impact on the quality of life. Anemia
also represents an important etiological factor in the development of left
ventricular hypertrophy. An inadequate production of a glycoprotein hormone,
erythropoietin (EPO), is the major cause of anemia in presence of a reduction in
the glomerular filtration rate. EPO is the primary regulator of the growth and
survival of the erythroid progenitor. The treatment of anemia in chronic renal
failure has been revolutionized by the introduction of recombinant human EPO.
The vast majority of patients responds very well to treatment, although 5-10% of
patients shows some resistance to EPO, the most common cause of which is iron
deficiency. Several studies have recently been started in order to investigate
the effects of preventing renal anemia from ever developing in uremic patients.
The hemoglobin concentration target in pre-dialysis and dialysis patients is the
subject of continuous re-assessment.
-----
Rev Med Suisse. 2005 Apr 13;1(15):1041-3, 1046-7.
[Anaemia treatment in gynaecology: use of epoetin in
onco-gynaecology and gynaecological surgery]
[Article in French]
Kirchner V; Anaemia Working Group.
FMH medecine interne, oncologie-hematologie, Clinique de Genolier 1272 Genolier.
In gynaecology, anaemia treatment is indicated in extremely different
situations. In cancer patients, treatment with epoetin can relieve fatigue and
improve quality of life. In these patients, epoetin treatment can also have a
positive influence on survival through increasing the efficacy of radiotherapy
and chemotherapy. Recent data are presented. In gynaecological surgery, the use
of epoetin--based on results in oncology and orthopaedic surgery--makes a
constructive contribution to the improvement of quality of life and during
patient recovery through rapid normalisation of perioperative anaemia, thus
reducing the risk of a transfusion with donated blood. Encouraging data from
recent publications concerning the prevention of PRCA under epoetin treatment
are presented.
-----
Best Pract Res Clin Haematol. 2005 Jun;18(2):319-32.
Diagnosis and management of iron-deficiency anaemia.
Cook JD.
Department of Medicine, University of Kansas Medical Center, 3901 Rainbow
Boulevard, Kansas City, KS 66160, USA.
Anaemia is typically the first clue to iron deficiency, but an isolated
haemoglobin measurement has both low specificity and low sensitivity. The latter
can be improved by including measures of iron-deficient erythropoiesis such as
the transferrin iron saturation, mean corpuscular haemoglobin concentration,
erythrocyte zinc protoporphyrin, percentage of hypochromic erythrocytes or
reticulocyte haemoglobin concentration. However, the changes in these
measurements with iron deficiency are indistinguishable from those seen in
patients with the anaemia of chronic disease. The optimal diagnostic approach is
to measure the serum ferritin as an index of iron stores and the serum
transferrin receptor as a index of tissue iron deficiency. The treatment of iron
deficiency should always be initiated with oral iron. When this fails because of
large blood losses, iron malabsorption, or intolerance to oral iron, parenteral
iron can be given using iron dextran, iron gluconate or iron sucrose.
-----
Nephrol Dial Transplant. 2005 Mar 15; [Epub ahead of print]
The efficacy and safety of weekly and fortnightly subcutaneous
epoetin {beta} in peritoneal dialysis patients with chronic renal anaemia.
Grzeszczak W, Sulowicz W, Rutkowski B, de Vecchi AF, Scanziani R, Durand PY,
Bajo A, Vargemezis V.
Silesian Medical University School, Nephrology Clinic, Zabrze, Poland.
BACKGROUND: Reducing the dosage of subcutaneous epoetin in peritoneal dialysis
(PD) patients is convenient and should improve patient satisfaction and,
possibly, compliance. We investigated if a weekly dosage of epoetin beta in PD
patients safely maintained haemoglobin (Hb) concentrations equivalent to those
obtained with twice- or thrice-weekly administration. In addition, we
investigated if a fortnightly dosage of epoetin beta was safe and as effective
as weekly administration. METHODS: After a 4 week run-in period, for 25 weeks PD
patients were switched to either weekly or fortnightly epoetin beta
administration, depending on their previous treatment schedules. RESULTS: The
per-protocol cohort included 128 patients, of whom 54 received epoetin beta once
weekly and 74 once fortnightly. The mean change in Hb concentration from
baseline over weeks 13-25 and the 90% confidence intervals (CIs) remained within
the target range (10-12 g/dl) and specified equivalence (+/-0.75 g/dl) limits in
the weekly (-0.34 g/dl; 90% CI: 0.14-0.54 g/dl) and fortnightly (-0.39 g/dl; 90%
CI: 0.24-0.55 g/dl) cohorts. The mean change from baseline in the epoetin beta
dose was 1.4 IU/kg/week (90% CI: -3.8 to 6.6 IU/kg/week; 2%) in the weekly
cohort and 4.4 IU/kg/week (90% CI: 1.7-7.2 IU/kg/week; 13%) in the fortnightly
cohort. Both treatment regimens were well tolerated. CONCLUSIONS: In stable PD
patients switched from twice- or thrice-weekly to weekly epoetin beta treatment,
Hb concentrations could be maintained within the specified range over 25 weeks
without significant change in their mean epoetin beta doses. In patients
switched from weekly to fortnightly treatment, Hb concentrations could also be
maintained over 25 weeks. There was a small increase in the mean dose during
this period, but >/=50% of patients could be maintained without increases in
their doses. Reducing dosage may improve compliance in PD patients who
self-administer their epoetin.
-----
Expert Opin Pharmacother. 2005 Feb;6(2):295-310.
Epoetin alfa for the treatment of cancer- and
chemotherapy-related anaemia: product review and update.
Henry DH.
Joan Karnell Cancer Center, Pennsylvania Hospital, 230 West Washington Square,
2nd Floor, Philadelphia, PA 19106, USA.
Anaemia, often associated with chemotherapy, is a common and debilitating
disorder in cancer patients. Recombinant human erythropoietin (epoetin alfa) was
introduced in the 1990s for the treatment of chemotherapy-related anaemia. Data
from randomised, double-blind, placebo-controlled studies and large, non-randomised,
community-based studies have demonstrated that either of the FDA-approved dosing
schedules of epoetin alfa 150 - 300 U/kg three times weekly or 40,000-60,000
U/week s.c., significantly increases haemoglobin levels, reduces transfusion
requirements, and improves quality of life in anaemic cancer patients undergoing
chemotherapy or chemoradiation therapy. Guidelines for the effective and safe
use of epoetin alfa have been published by major oncology/haematology
organisations and are reviewed in this article. Areas of recent and ongoing
investigation with epoetin alfa are also covered in this review.
-----
RCM Midwives. 2005 Feb;8(2):78-9.
Management of iron deficiency in pregnancy.
Ursell B.
This article reviews a study, published in Clinical and Laboratory Haematology
(2003), which looked at using iron-rich spa water (Spatone) as a prophylaxis
against iron deficiency in pregnancy. Anaemia is a significant problem in
pregnant women that can have a detrimental effect on the baby and mother. The
problems of non-compliance with oral iron supplements in this population are
well-documented. This was a prospective, randomised, double-blind,
placebo-controlled trial, and 102 patients were recruited into the study.
Inclusion criteria included singleton pregnancy, booking haemoglobin >10.4g/dl
and gestational age confirmed by ultrasound at 20 weeks. Primary outcome
measures were compliance with treatments during the trial period, ferritin
levels at 22 and 28 weeks and dyspepsia scores at 22 and 26 weeks. Results: Mean
ferritin levels fell by 24% in the Spatone group compared with a mean fall of
51% in ferritin levels in the control group, p = 0.016. In the Spatone group,
31% of patients raised their ferritin levels during the trial period compared
with 11% in the control group. The authors concluded that Spatone is effective
in maintaining iron stores in non-anaemic patients and is well-tolerated. The
study delivers a clear message to midwives--namely that Spatone has a place in
the management of iron-deficient pregnant women, because it is well-tolerated
and provides iron in a highly bioavailable form.
-----
Zhonghua Nei Ke Za Zhi. 2005 Jan;44(1):25-9.
[Improvement of left ventricular hypertrophy by anemic-correcting
erythropoietin therapy in chronic renal insufficiency.]
[Article in Chinese]
Jiang JP, Hou FF, Gao LZ, Pan YB, Yang NS, Chen W, Shu GY, Chen YM, Chen J, Peng
WH, Wu JP, Yang ZM.
Division of Nephrology, Nanfang Hospital, Guangzhou 510515, China.
OBJECTIVE: Left ventricular hypertrophy (LVH) is an independent predictor of
morbidity and mortality in dialysis patients. It remains unclear whether efforts
to correct anemia in patients with mild-to-moderate chronic renal insufficiency
(CRI) can reverse LVH. This prospective multi-center Chinese cohort study
evaluates left ventricular mass index (LVMI) evolution in anemic CRI patients
with or without recombinant human erythropoietin (rHuEPO) therapy. METHODS: Six
centers enrolled 158 patients with serum creatinine from 147 to 400 micromol/L,
and 86 of whom with hemoglobin (Hb) levels < 110 g/L received rHuEPO (Group A).
Forty patients with comparable Hb levels (< 110 g/L) but did not receive rHuEPO
(Group B) and those with Hb >/= 110 g/L (Group C, n = 32) were served as
controls. Echocardiographic studies were performed to evaluate LVMI at baseline
and every 3 months during a two-year period. RESULTS: At baseline, the
prevalence of LVH was 72.1% in Group A, 72.5% in Group B and 59.4% in Group C.
LVMI was inversely correlated with Hb levels (r = -0.70, P < 0.01). There was no
difference in age, gender, aetiology of renal failure, blood pressure (BP) and
cardiovascular risk factors between the 3 groups. The administration of rHuEPO
in Group A significantly increased Hb levels from (93.8 +/- 14.6) g/L to (111.2
+/- 10.3) g/L and decreased LVMI from (142.6 +/- 25.7) g/m(2) to (132.4 +/-
18.5) g/m(2). The prevalence of LVH decreased 16.3% after a partial correction
of anemia at 24 months, whereas Hb levels in controls (Group B and Group C)
tended to decrease and LVMI significantly increased compared with baseline. The
prevalence of LVH was significantly increased in Group B and C after 24 months.
The percentage of patients whose serum creatinine level doubled during the
follow-up was 3.4% in Group A, 15.0% in Group B and 9.4% in Group C, the
difference between Group A and Group B being significant (P < 0.05). In
addition, good BP control was obtained without any adverse effects. CONCLUSION:
High prevalence of LVH was present in pre-dialysis CRI patients, which is
associated with severity of anemia. Early treatment of anemia with rHuEPO can
reverse LVH in CRI patients.
-----
Rev Cardiovasc Med. 2005 Winter;6(1):1-10.
The deadly triangle of anemia, renal insufficiency, and
cardiovascular disease: implications for prognosis and treatment.
McCullough PA, Lepor NE.
Division of Cardiology, William Beaumont Hospital, Royal Oak, Michigan, USA.
Recently there has been considerable interest in the associations between blood
hemoglobin (Hb) level, renal function, and cardiovascular disease. Anemia is a
common feature of end-stage renal disease, but it also accompanies lesser
degrees of chronic kidney disease (CKD). The degree of anemia roughly
approximates the severity of CKD. Anemia seen in diabetes has been linked to
diabetic nephropathy; however, diabetes itself affects the hematologic system in
several ways. Anemia is associated with left ventricular hypertrophy,
cardiovascular morbidity, progressive loss of kidney function, and poor quality
of life. Anemia seems to act as a mortality multiplier; that is, at every
decrease in Hb below 12 g/dL, mortality increases in patients with CKD,
cardiovascular disease, and those with both. Unlike blood transfusion, treatment
of anemia with exogenous erythropoietin in patients with cardiorenal disease has
shown promise in reducing morbidity and in improving survival and quality of
life. Increasing the Hb level from less than 10 g/dL to 12 g/dL has resulted in
favorable changes in left ventricular remodeling, improved ejection fraction,
improved functional classification, and higher levels of peak oxygen consumption
with exercise testing. Clinical trials are underway to test the role of
erythropoietin in patients with CKD and in patients with heart failure.
-----
Semin Hematol. 2004 Oct;41(4 Suppl 7):17-25.
Preclinical and clinical studies: a preview of potential future
applications of erythropoietic agents.
Lewis LD.
Departments of Medicine/Pharmacology and Toxicology, Dartmouth Hitchcock Medical
Center, Lebanon, NH 03756, USA. Lionel.D.Lewis@Dartmouth.edu
Understanding the tissue distribution of erythropoietin receptors and cellular
actions of erythropoietic agents may facilitate the development of wider
applications for these compounds. Erythropoietin receptors have been identified
in the central nervous system (CNS), retina, heart, vascular endothelium,
kidney, lung, liver, gastrointestinal and reproductive tracts, and erythroid
bone marrow precursors. Potential benefits of erythropoietic agents in several
therapeutic areas may result from actions other than hematopoiesis stimulation.
Their hematopoietic effects may also have broader applications in treating
anemia of the elderly and non-chemotherapy (CT)-related anemia in patients with
cancer. Furthermore, because hypoxic tumor cells tend to be more resistant to
radiation therapy (RT) and some forms of CT, and more aggressive than normoxic
cells, increased oxygenation resulting from anemia correction may increase RT
and CT sensitivity, possibly impacting treatment outcomes. However, clinical
studies addressing this hypothesis have conflicting results. Preliminary
evidence suggests erythropoietin has CNS neuroprotective effects, including
potential clinical benefits in ischemic stroke. In addition, data suggest that
erythropoietin (epoetin alfa) may attenuate declines in cognitive function
during CT for early-stage breast cancer. Erythropoietin may have benefits in
retinal disease, peripheral neuropathy, and myocardial ischemia. Thus,
accumulating evidence suggests that erythropoietic agents may have clinical
utility outside CT-related anemia.
-----
Am J Transplant. 2004 Dec;4(12):2001-6.
Comparative effects of sirolimus and mycophenolate mofetil on
erythropoiesis in kidney transplant patients.
Augustine JJ, Knauss TC, Schulak JA, Bodziak KA, Siegel C, Hricik DE.
Department of Nephrology, Case Western University Hospitals, Cleveland, OH, USA.
joshua.augustine@uhhs.com
Anemia and erythrocytosis (PTE) are common after kidney transplantation. We
sought to determine the influence of sirolimus compared to mycophenolate mofetil
(MMF) on post-transplant erythropoiesis. A total of 214 patients with recent
kidney or kidney-pancreas transplants were treated with either sirolimus-based
(n = 87) or MMF-based (n = 127) therapy. At 12 months, the prevalence of anemia
was 31% with MMF and 57% with sirolimus (p < 0.001). Linear regression was used
to examine the independent influence of sirolimus on hemoglobin at 12 months,
controlling for multiple factors including gender and renal function. Sirolimus
remained a significant correlate of lower hemoglobin in all patients (slope
=-1.060, 95% CI: -1.76 to -0.362, p = 0.003), and in patients without PTE (slope
=-0.671, 95% CI: -1.32 to -0.028, p = 0.041). PTE, defined as a persistent
hematocrit above 51%, occurred in 19% with MMF and 7% with sirolimus (p =
0.013). PTE was examined using logistic regression analysis. Sirolimus use
correlated negatively with PTE (odds ratio with sirolimus = 0.33, 95% CI: 0.12
to 0.89, p = 0.028). Our results indicate that, compared to treatment with MMF,
treatment of kidney or kidney-pancreas recipients with sirolimus is associated
with a higher prevalence of anemia, lower hemoglobin levels and lower incidence
of PTE.
------
Schweiz Rundsch Med Prax. 2004 Nov 10;93(46):1905-10.
[Erythropoietin and intravenous iron to save blood in surgery]
[Article in German]
Beris P; Anemia Working Group.
Departement de Medecine Interne, Hopital Cantonal, Geneve. Photis.Beris@hcuge.ch
Recombinant human erythropoietin (rHuEPO) and intravenous (i.v.) iron
administration may be useful tools to save blood in surgery. In the
perioperative period, rHuEPO should be used in slightly anemic patients for whom
an autologous predonation program is not recommended (or feasible). In such
cases, i.v. iron is only given if there is a functional or real iron deficiency
state. In the post-operative period, i.v. iron is administered in association
with rHuEPO in an attempt to rapidly correct severe post-operative anemia. The
same regimen is used for patients undergoing surgery for inflammatory bowel
disease and rheumatoid arthritis. Finally, other particular categories of
patients, such as those with reduced body weight (< 50 kg), candidates for
surgery with increased blood needs (> 5 units), or those with a too-short period
of time before surgery, also benefit from the administration of these two drugs.
-----
Indian J Pediatr. 2004 Nov;71(11):1015-9.
Controlling iron deficiency anemia through the use of
home-fortified complementary foods.
Zlotkin SH, Christofides AL, Ziauddin Hyder SM, Schauer CS, Tondeur MC, Sharieff
W.
Departments of Pediatrics, Nutritional Sciences and Health Policy, Management
and Evaluation and Centre for International Health, University of Toronto,
Canada. Stanley.Zlotkin@sickkids.ca.
Iron deficiency anemia (IDA) is more common in South Asian countries including
India, Bangladesh and Pakistan than anywhere else in the world. During infancy
and early childhood, IDA is associated with impaired psycho-motor development
and cognitive function that may be irreversible. As a consequence, there is a
growing awareness that IDA is one of many factors impeding socio-economic
prosperity of developing nations. The combination of unacceptably high
prevalence rates and inadequate preventative programs highlights the need for
new effective sustainable strategies to control IDA. The burden of iron
deficiency can be reduced by taking a more holistic approach that would include
promotion of healthy weaning practices and use of appropriate complementary
foods, together with improving the nutritional value of such foods. There is an
increasing body of peer-reviewed literature to support the contention that
"micronutrient Sprinkles" is an effective strategy to improve the nutritional
value of home-prepared complementary foods and thus to reduce the burden of iron
deficiency among children. By combining data from recently conducted randomised
control trials, Sprinkles were shown to be as efficacious as iron drops for
treating childhood anemia. The iron in Sprinkles is well absorbed, and Sprinkles
are easy to use and well accepted by young children and their caregivers.
Integrated into existing public health programs, Sprinkles has the potential to
improve the effectiveness of such programs.
-----
Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004222.
Treatment for women with postpartum iron deficiency anaemia.
Dodd J, Dare M, Middleton P.
Department of Obstetrics and Gynaecology, University of Adelaide, Women's and
Children's Hospital, 72 King William Road, Adelaide, South Australia, AUSTRALIA,
5006.
BACKGROUND: Postpartum anaemia is associated with breathlessness, tiredness,
palpitations and maternal infections. Blood transfusions or iron supplementation
have been used in the treatment of iron deficiency anaemia. Recently other
anaemia treatments, in particular erythropoietin therapy, have also been used.
OBJECTIVES: To assess the clinical effects of treatments for postpartum anaemia,
including oral, intravenous or subcutaneous iron/folate supplementation and
erythropoietin administration, and blood transfusion. SEARCH STRATEGY: We
searched the Cochrane Pregnancy and Childbirth Group trials register (30 May
2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003),
Current Contents and ACP Journal Club (from inception to March 2003). SELECTION
CRITERIA: Randomised controlled trials (RCTs) comparing therapy for postpartum
iron deficiency anaemia (oral, intravenous or subcutaneous administration of
iron, folate, erythropoietin or blood transfusion) with placebo, another
treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers
independently assessed trial quality and extracted data. MAIN RESULTS: Six
included RCTs involving 411 women described treatment with erythropoietin or
iron as their primary interventions. No RCTs were identified that assessed
treatment with blood transfusion. Few outcomes relating to clinical maternal and
neonatal factors were reported: studies focused largely on surrogate outcomes
such as haematological indices. Overall, the methodological quality of the
included RCTs was reasonable; however, their usefulness in this review is
restricted by the interventions and outcomes reported.When compared with iron
therapy only, erythropoietin increased the likelihood of lactation at discharge
from hospital (1 RCT, n = 40; relative risk (RR) 1.90, 95% confidence interval
(CI) 1.21 to 2.98). No apparent effect on need for blood transfusions was found,
when erythropoietin plus iron was compared to treatment with iron only (2 RCTs,
n = 100; RR 0.20, 95% CI 0.01 to 3.92), although the RCTs may have been of
insufficient size to rule out important clinical differences. Haematological
indices (haemoglobin and haemocrit) showed some increases when erythropoietin
was compared to iron only, iron and folate, but not when compared with placebo.
REVIEWERS' CONCLUSIONS: There is some limited evidence of favourable outcomes
for treatment of postpartum anaemia with erythropoietin. However, most of the
available literature focuses on laboratory haematological indices, rather than
clinical outcomes. Further high-quality trials assessing the treatment of
postpartum anaemia with iron supplementation and blood transfusions are
required. Future trials may also examine the significance of the severity of
anaemia in relation to treatment, and an iron-rich diet as an intervention.
-----
J Nephrol. 2004 Sep-Oct;17(5):687-92.
A trial of subcutaneous administration of darbepoetin alfa once
every other week for the treatment of anemia in
peritoneal dialysis patients.
Mahajan S, Boulton H, Gokal R.
All India Institute of Medical Sciences, New Delhi - India.
Background: Darbepoetin alfa (Aranesp, Amgen) is an erythropoietic stimulating
protein with a three fold longer terminal half life than recombinant human
erythropoietin (rHuEPO). The purpose of this single center, single arm study was
to determine whether darbepoetin alfa is as effective as rHuEPO for the
treatment of renal anemia in patients on peritoneal dialysis when administered
at a reduced dosing frequency of once every other week irrespective of the
initial rHuEPO dose frequency. Methods: A total of 17 patients on peritoneal
dialysis receiving stable rHuEPO therapy were changed to darbepoetin alfa every
other week, using the recommended 200:1 conversion factor . The doses of
darbepoetin alfa were titrated to maintain hemoglobin within -1.0 to +1.5 g/dL
of the patients' baseline value and also within a range of 10.0 to 13.0 g/dL for
up to 24 weeks (20 weeks dose titration period followed by 4 week evaluation
period). The primary end point was change in hemoglobin levels between baseline
and evaluation period. Results: Mean change in hemoglobin levels from baseline
to evaluation period was 0.03 g/dL (95% CI -0.62 to +0.69). This was not a
statistically significant or clinically relevant difference, despite the reduced
frequency of darbepoetin alfa administration. There were no serious or major
adverse effects observed with darbepoetin alfa during the study. Conclusion:
These results show that darbepoetin alfa maintains hemoglobin concentrations
effectively and safely in patients on peritoneal dialysis, but with a reduced
dose frequency as compared to rHuEPO.
-----
Bull Acad Natl Med. 2004;188(3):491-505; discussion 505-6.
[Sickle cell disease in childhood in 2004]
[Article in French]
Girot R, Begue P.
Service d'Hematologie, Hopital Tenon 4, rue de la Chine, 75020 Paris.
Sickle cell disease is a genetic autosomal recessive disease of hemoglobin. The
disease results from a mutation of the sixth codon of the beta-globin gene,
which induces the synthesis of an abnormal hemoglobin called hemoglobin S (HbS).
The polymerisation of deoxy HbS molecules causes a chronic hemolytic anemia and
vaso-occlusive phenomena. The disease affects mainly people from West Indies and
Sub Saharan Africa. Due to recent movements of these populations over the past
years, sickle cell disease has spread across all continents. Painful crises,
severe infections such as septicemia, meningitis, osteomyelytis, acute anemia
episodes, and severe vaso-occlusive events, mainly neurological, are the most
frequent complications affecting children. Recent progresses in the care of
patients have deeply modified the prognosis. The mean life expectancy of
patients is now above 40 years. The conventional treatment includes antibiotics
and immunizations, analgesics, and blood transfusion. The effects of chronic
blood transfusion, hydroxyurea and bone marrow transplantation are the subject
of current comparative evaluations.
-----
Oncologist. 2004;9(6):696-707.
A randomized comparison of every-2-week darbepoetin alfa and
weekly epoetin alfa for the treatment of chemotherapy-induced anemia in patients
with breast, lung, or gynecologic cancer.
Schwartzberg LS, Yee LK, Senecal FM, Charu V, Tomita D, Wallace J, Rossi G.
The West Clinic, 100 North Humphreys Boulevard, Memphis, Tennessee 38120, USA.
lschwartzberg@westclinic.com
An important clinical question is the relative efficacy of the most common
dosages of darbepoetin alfa (Aranesp; Amgen Inc.; Thousand Oaks, CA) 200 microg
every 2 weeks (Q2W) and epoetin alfa (Procrit; Ortho Biotech Products, LP;
Raritan, NJ) 40,000 U weekly (QW) for the treatment of chemotherapy-induced
anemia. We designed three concurrent randomized, open-label, multicenter,
identical trials (with the exception of tumor type criteria of breast,
gynecologic, or lung cancer) of darbepoetin alfa and epoetin alfa in patients
with chemotherapy-induced anemia to validate the Patient Satisfaction
Questionnaire for Anemia (PSQ-An) treatment tool and to compare the efficacies
and safety profiles of these two agents. In each trial, patients were randomized
1:1 to receive either darbepoetin alfa at a dose of 200 microg Q2W or epoetin
alfa at a dose of 40,000 U QW for up to 16 weeks. The PSQ-An was assessed for
validity, feasibility, and reliability. Secondary clinical endpoints were
analyzed using the primary analysis set. Both individual trial analyses and a
protocol-specified combined analysis of data from all three trials were
conducted. Overall, 312 patients (157 darbepoetin alfa; 155 epoetin alfa) were
randomized and received study drug. Baseline characteristics were similar in
both treatment groups in each trial and overall. The PSQ-An was valid, feasible,
and reliable. In general, no difference between treatment groups was observed
for hemoglobin- and transfusion-based endpoints in each individual trial or in
the combined analysis. From exploratory analyses, achievement and maintenance of
a hemoglobin target range (11-13 g/dl) were similar in both groups. No
differences in safety were observed. With the PSQ-An, formal comparisons of the
impact of anemia therapies on patients and caregivers can be made in future
prospective studies. Further, darbepoetin alfa (200 microg Q2W) and epoetin alfa
(40,000 U QW) appear to achieve comparable clinical and hematologic outcomes.
-----
Hematology (Am Soc Hematol Educ Program). 2004;:318-36.
Marrow failure.
Bagby GC, Lipton JM, Sloand EM, Schiffer CA.
New discoveries in cell biology, molecular biology and genetics have unveiled
some of the pathophysiological mysteries of some of the bone marrow failure
syndromes. Many of these discoveries have revealed why these syndromes show so
much clinical overlap and some hold the potential for influencing the
development of new therapies. In children and adults with pancytopenia and
hypoplastic bone marrows proper differential diagnosis requires that some
attention be directed toward defining molecular and cellular pathogenetic
mechanisms because, once identified, some of these mechanisms will clearly
suggest rational therapeutic approaches, treatment options that should be
avoided, or both.In Section I, Drs. Jeffrey Lipton and Grover Bagby review the
approach to diagnosis and management of patients with the inherited bone marrow
failure syndromes, Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan
anemia, and the Shwachman-Diamond syndrome. Extraordinary progress has been made
in identifying the genes bearing pathogenetically relevant mutations in these
disorders, but slower progress has been made in defining the precise functions
of the proteins these genes encode in normal cells, in part because it is
increasingly obvious that the proteins are multifunctional. In practice, it is
clear that in patients with dyskeratosis congenita and Fanconi anemia, the
diagnosis must be considered not only in children but in adults as well.In
Section II, Dr. Elaine Sloand outlines a very practical and evidence-based
approach to diagnosis and management of acquired hypoplastic states emphasizing
overlap between non-clonal and clonal hematopoiesis is such conditions. The
pathogenesis of T lymphocyte-mediated marrow failure is presented as a clear-cut
rationale for use of immunosuppressive therapy and stem cell transplantation.
Practical management of patients with refractory disease with and without
evidence of clonal evolution (either paroxysmal nocturnal hemoglobinuria [PNH]
or myelodysplasia [MDS]) is presented.In Section III, the challenge of
hypoplastic MDS is reviewed by Dr. Charles Schiffer. After reviewing the most
up-to-date classification scheme, therapeutic options are reviewed, focusing
largely on agents that have most recently shown some promising activity,
including DNA demethylating agents, thalidomide and CC5013, arsenic trioxide,
and immunosuppressive therapy. Here are also outlined the rationale and the
indications for choosing allogeneic bone marrow transplantation, the only
therapy with known curative potential.
-----
Hematology (Am Soc Hematol Educ Program). 2004;:35-47.
Sickle cell disease.
Buchanan GR, Debaun MR, Quinn CT, Steinberg MH.
Much progress has been made during the past several decades in gaining
understanding about the natural history of sickle cell disease and management
approaches aimed at treating or even preventing certain disease complications.
The characterization of the human genome now offers the opportunity to
understand relationships regarding how gene polymorphisms as well as how
environmental factors affect the sickle cell disease phenotype, i.e., the
individual patient's overall clinical severity as well as their specific organ
function. This chapter explores some of these recent advances in knowledge. In
Section I, Dr. Michael DeBaun characterizes the problem of silent stroke in
sickle cell disease, comparing and contrasting its clinical and neuroimaging
features with overt stroke. Combined, these events affect virtually 40% of
children with sickle cell anemia. New understanding of risk factors, associated
clinical findings, and imaging technologies are impacting substantially on
treatment options. The appreciable cognitive dysfunction and other sequelae of
silent infarct demand more effective treatments and ultimate prevention. In
Section II, Dr. Charles Quinn addresses the conundrum of why some patients with
sickle cell disease do well whereas others fare poorly. Some risk factors have
been known for years, based upon careful study of hundreds of patients by the
Cooperative Study for Sickle Cell Disease and investigators studying the
Jamaican newborn cohort. Other prognostic measures have only recently been
defined. Dr. Quinn devotes special attention to stroke and chest syndrome as
organ-related complications but also describes attempts to measure overall
disease severity and to predict survival. Recently, investigators have attempted
to predict factors responsible for early mortality in children and following
onset of pulmonary hypertension in adults. In Section III, Dr. Martin Steinberg
reviews pharmacologic approaches to sickle cell disease and the rationale for
their use. In addition to the inhibition of hemoglobin S polymerization, newer
targets have been defined during the past one to two decades. These include the
erythrocyte membrane, changes in the red cell intracellular content (especially
loss of water), endothelial injury, and free radical production. Hydroxyurea
treatment attracted the greatest interest, but many uncertainties remain about
its long-term benefits and toxicities. Newer "anti-sickling" agents such as
decitabine and short-chain fatty acids also receive attention. Prevention of red
cell dehydration, "anti-endothelial" therapy, and marshaling the potentially
beneficial effects of nitric oxide are other new and exciting approaches.
-----
Congest Heart Fail. 2004 Sep-Oct;10(5):243-7.
Mechanisms and treatment of anemia in chronic heart failure.
Katz SD.
Yale University School of Medicine, 135 College Street, Suite 301, New Haven, CT
06510. stuart.katz@yale.edu.
Anemia is highly prevalent in patients with chronic heart failure (HF) and is
associated with poor clinical outcomes. Multiple mechanisms contribute to anemia
in chronic HF, and subnormal compensatory rise in endogenous erythropoietin
levels in response to anemia is one contributory factor. Randomized trials with
recombinant human erythropoietin therapy in anemic patients with chronic kidney
disease and concomitant heart disease have demonstrated a reduction in left
ventricular hypertrophy but variable effects on clinical outcome. Preliminary
clinical trials in anemic patients with chronic HF demonstrate that
erythropoietin therapy is well tolerated and associated with short-term clinical
improvement. The optimum target hemoglobin, erythropoietic agent, and dosing
regimen, and the role of iron supplementation in patients with chronic HF, are
not known. Additional studies are needed to determine the safety and efficacy of
long-term erythropoietic therapy in chronic HF patients.
-----
Crit Care. 2004 Oct;8(5):356-62. Epub 2004 May 13.
Bench-to-bedside review: Iron metabolism in critically ill
patients.
Darveau M, Denault AY, Blais N, Notebaert E.
Research student, Faculty of Pharmacy, University of Montreal, Quebec, Canada.
martin_darveau@ssss.gouv.qc.ca.
Critically ill patients frequently develop anemia due to several factors.
Iron-withholding mechanisms caused by inflammation contribute to this anemia.
The iron metabolism imbalances described or reported in all intensive care
studies are similar to the values observed in anemia of inflammation. The
administration of iron could be useful in the optimization of recombinant human
erythropoietin activity, but this could be at the expense of bacterial
proliferation. Since there is a lack of evidence to support either oral or
intravenous iron administration in intensive care patients, further studies are
necessary to determine the efficacy and safety of iron supplementation in
conjunction with recombinant human erythropoietin in critically ill patients. We
review the mechanisms leading to iron sequestration in the presence of
inflammation. The present article also reviews the literature describing the
iron status in critically ill patients and explores the role of iron
supplementation in this setting.
-----
Crit Care. 2004 Oct;8(5):325-6. Epub 2004 Sep 06.
Erythropoietin in the critically ill - is it more than just
blood?
Corwin HL.
Professor of Medicine and Anesthesiology, Dartmouth Medical School, Section
Chief, Critical Care Medicine, Medical Director, Intensive Care Unit,
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. Howard.L.Corwin@hitchcock.org.
Erythropoietin (EPO) has been in clinical use for the treatment of anemia for
over 15 years. Recently it has been demonstrated that EPO has actions other than
stimulating the bone marrow. It has been suggested that due to its tissue
protecting effect, EPO may be effective in improving outcome in the critically
ill.
-----
J Clin Oncol. 2004 Sep 27 [Epub ahead of print]
Phase III, Randomized, Double-Blind Study of Epoetin Alfa Versus
Placebo in Anemic Patients With Cancer Undergoing Chemotherapy.
Witzig TE, Silberstein PT, Loprinzi CL, Sloan JA, Novotny PJ, Mailliard JA,
Rowland KM, Alberts SR, Krook JE, Levitt R, Morton RF.
Department of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN.
PURPOSE: To determine whether weekly epoetin alfa could improve hemoglobin (HgB)
levels, reduce RBC transfusions, and improve quality of life (QOL) in patients
with advanced cancer and with anemia after receiving myelosuppressive
chemotherapy. PATIENTS AND METHODS: This double-blind, placebo-controlled study
randomly assigned patients to placebo or epoetin alfa (Ortho Biotech,
Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC
transfusions were measured pretreatment and monthly. RESULTS: The study accrued
344 patients; 330 were assessable for efficacy and 305 were assessable for QOL.
Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to
+5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients
(P <.0001). During the study, 31.7% of placebo-treated patients achieved a >/= 2
g/dL HgB increase compared with 72.7% of epoetin-treated patients (P <.0001).
The incidence of RBC transfusion for placebo and epoetin treatment arms was
39.6% and 25.3% (P =.005), respectively. The placebo group received 256 units of
RBCs compared with 127 units in the epoetin group (P <.0001). The incidence of
toxicity in the groups was similar. Changes in the average QOL scores from
baseline to the end of the study were similar in the two groups (P = not
significant). The HgB responders (irrespective of treatment arm) had a mean
change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a
baseline of +5.1 compared with -2.1 for the nonresponders (P =.006). CONCLUSION:
Epoetin alfa significantly improved HgB and reduced transfusions in this patient
population. These results support the use of weekly epoetin alfa as an
ameliorative agent for cancer-related anemia.
-----
Haematologica. 2004 Sep;89(9):ECR34.
Sustained response to rituximab of autoimmune hemolytic anemia
associated with antiphospholipid syndrome.
Erdozain JG, Ruiz-Irastorza G, Egurbide MV, Aguirre C.
Service of Internal Medicine, Hospital de Cruces, 48903 Bizkaia, Spain.
Standard treatment for autoimmune hemolytic anemia (AIHA) due to warm antibodies
includes combinations of glucocorticoids, immunosuppressive drugs (mainly
azathioprine) and splenectomy. Patients who are refractory or intolerant to
these therapies constitute an important therapeutic challenge. Rituximab, an
anti-CD20 chimeric monoclonal antibody, can effectively deplete B-cells and is
commonly used in B-cell non-Hodgkin lymphoma. In addition, it is being
increasingly used in autoimmune disorders, such as idiopathic thrombocytopenic
purpura, AIHA, systemic lupus erythematosus or vasculitis. We report a case of
warm AIHA associated to primary antiphospholipid syndrome (APS). The patient was
refractory to high-dose corticosteroids. Splenectomy was discarded in view of
the high risk of thrombotic and/or hemorrhagic perioperative complications, due
to the presence of APS. After treatment with four weekly doses of rituximab the
patients had a rapid and sustained response which allowed progressive tapering
of prednisone dose to 5 mg/d. In addition, IgM anticardiolipin titres decreased
from > 600 MPL to < 100 MPL. Thirteen further cases of warm AIHA in adults
treated with rituximab have been reviewed, showing excellent tolerance and high
response rates. Rituximab may be considered prior to splenectomy in patients
with refractory AIHA and high risk of complications following splenectomy.
-----
Haematologica. 2004 Sep;89(9):1054-61.
Treatment of severe aplastic anemia with antilymphocyte globulin,
cyclosporine and two different granulocyte colony-stimulating factor regimens: a
GITMO prospective randomized study.
Locasciulli A, Bruno B, Rambaldi A, Saracco P, Dufour C, Finelli C, Sica S,
Varotto S, Arcese W, Locatelli F, Soligo D, Bacigalupo A.
Ematologia e Trapianto di Midollo, Ospedale San Camillo, Circonvallazione
Gianicolense 87, 00152 Rome, Italy. annabri@libero.it; alocasciulli@scamilloforlanini.rm.it
BACKGROUND AND OBJECTIVES: In a previous study we showed that patients with
severe aplastic anemia (SAA) treated with anti-lymphocyte globulin (ALG),
cyclosporin (CyA) and granulocyte colony-stimulating factor (G-CSF) 5 micro
g/kg/day had an encouraging outcome. However, failure to respond, delayed
responses, partial responses, relapses and early deaths remain signifcant
problems. The aim of the present study was to test whether a higher dose of G-CSF
(10 micro g/kg/day) would reduce these complications. DESIGN AND METHODS: This
was a multicenter prospective trial in 77 SAA patients treated with horse ALG
(15 mg/kg/day day1-5) and CyA (5 mg/kg/day day 1-180). Patients were randomized
to receive G-CSF 5 micro g/kg/day (n=38, group A) or 10 micro g/kg/day (n=39,
group B) from day +1 to day +30. All patients then received G-CSF 5 micro
g/kg/day from day +31 to day +90. The primary end point of this study was
response at day +120. Secondary end points were early deaths, blood counts at
day +120, and survival. RESULTS: At day +120 responses were classified as
absent, partial, and complete in 12, 22, and 4 patients in group A and in 23, 7,
and 9 patients in group B (p=0.001). At last follow-up these figures were
respectively 9, 12, and 17 vs 19, 2, and 18 (p=0.004). Thirteen patients (5 in
group A and 8 in group B) died before day 120 (p=0.3). Median peripheral blood
counts on day 120 were comparable in the two groups: Hb 10.5 and 9.5 g/dL in
group A and B, respectively (p=0.6), Neutrophil counts were 2.4 vs 1.9x109/L in
groups A and B (p=0.4) and platelet counts were, respectively, 42 vs 36x109/L
(p=0.3). The actuarial survival at 4 years is 72% in group A and 67% in group B
(p=0.3). INTERPRETATION AND CONCLUSIONS: Increasing the dose of G-CSF does not
appear to reduce early deaths, does not improve peripheral blood counts nor
survival, and may reduce the response rate in patients with SAA receiving ALG
and CyA.
-----
Gynecol Obstet Fertil. 2004 Jul-Aug;32(7-8):613-9.
[Acute postpartum anaemia. Clinical practice and interest of
intravenous iron]
[Article in French]
Broche DE, Gay C, Armand-Branger S, Grangeasse L, Terzibachian JJ.
Service de gynecologie-obstetrique, centre hospitalier, 14, rue de Mulhouse, BP
499, 90016 Belfort cedex, France.
OBJECTIVES: Postpartum anaemia is a very frequent pathology concerning from 4%
to 27% of patients. The purpose of this study was to estimate clinical practice
in front of acute postpartum anaemia and to value a new treatment: intravenous
iron. PATIENTS AND METHODS: Retrospective study over a period of 2 years (April
2001-March 2003) realised in the Department of Gynaecology and Obstetrics of
Belfort Regional Hospital. Two hundred and seventeen patients were included (5%
of deliveries in the same period) with immediate postpartum period haemoglobin
<8 g/dl. Two groups were individualised according to the availability or not of
an intravenous iron therapy. Clinical and biologic elements concerning
deliveries were analysed. RESULTS: Average haemoglobin values, from delivery to
48 h after it, were 5.81 g/dl for blood-transfused patients, 6.88 g/dl for
intravenous iron treated patients and 7.43 g/dl for oral iron treated patients.
Fifteen patients were transfused during the year before the launch of
intravenous iron as a possible therapy and only five patients the next year. The
benefit of haemoglobin values with an intravenous iron therapy was 1.9 g/dl on 7
days and 3.1 g/dl on 14 days. DISCUSSION AND CONCLUSION: These results suggest a
real efficiency of intravenous iron therapy for acute postpartum anaemia (haemoglobin
values <8 g/dl) with a good tolerance. Patients with haemoglobin values <7 g/dl
treated by intravenous iron tend to show that some blood transfusions would be
thereby avoided even though blood transfusion remains the urgency treatment.
-----
J Nephrol. 2004 Jul-Aug;17(4):487-95.
Intravenous iron therapy in renal failure: friend and foe?
Afzali B, Goldsmith DJ.
Nephrology and Transplantation, Guy's Hospital, London, UK.
Anemia is a common feature of chronic renal dysfunction and is associated with
significant morbidity and mortality. Although acquired insufficiency of
erythropoietin is virtually universal, iron deficiency is also a common
contributor to the development of anemia. Iron replacement, in particular via
the intravenous route, has become commonplace and results in improved
hematocrits either on its own or in association with an erythropoiesis
stimulating agent. However, intravenous iron is not without its potential
complications. These include acute allergic reactions, iron overload,
potentially accelerated cardiovascular disease and risk of infection. It is the
purpose of this review to critically evaluate the available clinical and
experimental evidence linking iron supplementation therapy with these
complications.
-----
Nutrition. 2004 Jul-Aug;20(7-8):632-44.
Vitamin and mineral status: effects on physical performance.
Lukaski HC.
U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human
Nutrition Research Center, Grand Forks, North Dakota, USA.
Public health recommendations encourage the selection of a balanced diet and
increasing physical activity to foster health and well-being. Whereas the
adverse effects of restricted intakes of protein, fat, and carbohydrate on
physical performance are well known, there is limited information about the
impact of low intakes of vitamins and minerals on the exercise capacity and
performance of humans. Physically active people generally consume amounts of
vitamins and minerals consistent with the recommendations for the general
public. However, when intakes are less than recommendations, some noticeable
functional impairments occur. Acute or short-term marginal deficiencies,
identified by blood biochemical measures of vitamin B status, had no impacts on
performance measures. Severe deprivation of folate and vitamin B12 result in
anemia and reduce endurance work performance. Evidence of vitamin A and E
deficiencies in athletic individuals is lacking apparently because body storage
is appreciable. In contrast to vitamins, marginal mineral deficiencies impair
performance. Iron deficiency, with or without anemia, impairs muscle function
and limits work capacity. Magnesium deprivation increases oxygen requirements to
complete submaximal exercise and reduces endurance performance. Use of vitamin
and mineral supplements does not improve measures of performance in people
consuming adequate diets. Young girls and individuals participating in
activities with weight classifications or aesthetic components are prone to
nutrient deficiencies because they restrict food intake and specific
micronutrient-rich foods. This information will be useful to professionals who
counsel physically active people and scientific groups who make dietary
recommendations to improve health and optimize genetic potential.
-----
Blood. 2004 Jul 6 [Epub ahead of print]
The prevalence of anemia in persons age 65 and older in the
United States: evidence for a high rate of unexplained anemia.
Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC.
National Institute on Aging, National Insitutes of Health, Bethesda, MD, USA.
Clinicians frequently identify anemia in their older patients, but U.S. national
data on the prevalence and causes of anemia in this population have not been
available. Data are from the non-institutionalized U.S. population assessed in
the third National Health and Nutrition Examination Survey (1988-1994). Anemia
was defined by World Health Organization criteria; causes of anemia included
iron, folate and B12 deficiencies, renal insufficiency, anemia of chronic
inflammation (ACI), formerly termed anemia of chronic disease, and unexplained
anemia (UA). ACI by definition required normal iron stores with low circulating
iron (< 60 micro g/dl). After age 50, anemia prevalence rates rose rapidly, to a
prevalence above 20% at age 85 and older. Overall, 11.0% of men and 10.2% of
women age 65 and older were anemic. Evidence of nutrient deficiency was present
in one-third of older persons with anemia, ACI and/or chronic renal disease in
one-third, and UA in the remaining one-third. Most anemia was mild; 2.8% of
women and 1.6% of men had hemoglobin < 11g/dl. Therefore, anemia is common,
albeit not severe, in the older population, and a substantial proportion of
anemia is of indeterminate cause. The impact of anemia on quality of life,
recovery from illness, and functional abilities needs to be further investigated
in older persons.
-----
J Am Soc Nephrol. 2004 Jul;15(7):1877-82.
Pentoxifylline improves hemoglobin levels in patients with
erythropoietin-resistant
anemia in renal failure.
Cooper A, Mikhail A, Lethbridge MW, Kemeny DM, Macdougall IC.
Department of Renal Medicine, GKT School of Medicine, King's College Hospital,
London, United Kingdom.
It was hypothesized that pentoxifylline might improve the response to
recombinant human erythropoietin (rh-Epo) in anemic renal failure patients.
Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin
of <10.7 g/dl for 6 mo before treatment and a rh-Epo dose of > or =12,000 IU/wk,
were recruited. They were treated with oral pentoxifylline 400 mg o.d. for 4 mo.
Ex vivo T cell generation of tumor necrosis factor alpha (TNF-alpha) and
interferon gamma (IFN-gamma) from the patients was assessed before treatment and
6 to 8 wk after therapy. A total of 12 of 16 patients completed the study.
Before therapy, the 12 patients' mean hemoglobin concentration was 9.5 +/- 0.9
g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration
increased to 11.7 +/- 1.0 g/dl (P = 0.0001). Baseline ex vivo T cell expression
of TNF-alpha decreased from 58% +/- 11% to 31% +/- 23% (P = 0.0007) after
therapy. Likewise, IFN-gamma expression decreased from 31% +/- 10% to 13% +/-
10% (P = 0.0002). Pentoxifylline therapy may significantly improve the
hemoglobin response in patients with previously rh-Epo-resistant anemia in renal
failure. This may occur due to inhibition of proinflammatory cytokine
production, which could interfere with the effectiveness of rh-Epo.
-----
Pediatrics. 2004 Jul;114(1):86-93.
Daily multivitamins with iron to prevent anemia in high-risk
infants: a randomized clinical trial.
Geltman PL, Meyers AF, Mehta SD, Brugnara C, Villon I, Wu YA, Bauchner H.
Department of Pediatrics, Boston University School of Medicine and Boston
Medical Center, Boston, Massachusetts, USA. pgeltman@bu.edu
OBJECTIVE: The goal of this study was to assess the effectiveness of
multivitamins with iron as prophylaxis against iron deficiency and anemia in
infancy. METHODS: The study was a double-blinded, randomized, pragmatic,
clinical trial conducted at 3 urban primary care clinics. Subjects included
healthy, full-term infants who were enrolled at their 6-month well-child visit.
Infants were randomly assigned to receive standard-dose multivitamins with or
without iron (10 mg/day). Parents administered multivitamins by mouth daily for
3 months. Laboratory results at 9 months of age were analyzed for the presence
of anemia and/or iron deficiency. Anemia was defined as hemoglobin level <11.0
g/dL. Iron deficiency was initially defined as any abnormal laboratory value of
the following: mean corpuscular volume combined with red cell distribution width
or zinc protoporphyrin (with blood lead level <10 microg/dL) for most subjects
and ferritin, transferrin saturation, or reticulocyte hemoglobin content for a
subset. Subsequent analyses defined iron deficiency as any 2 abnormalities of
the above laboratory outcomes, except hemoglobin. RESULTS: The control (n = 138)
and intervention (n = 146) groups were equivalent with respect to all important
sociodemographic and nutritional variables. At 9 months of age, anemia was found
in 21% of infants (n = 58). A total of 229 (81%) had iron deficiency on the
basis of 1 abnormal laboratory indicator and 139 (49%) on the basis of 2
abnormal laboratory indicators. No difference existed in the occurrence of
anemia and iron deficiency between the intervention and control groups. In the
intervention group, 22% and 78% of 138, respectively, were anemic or had 1
abnormal laboratory outcome indicative of iron deficiency. In the control group,
19% and 84% of 144 were anemic or iron deficient. When stratified by adherence,
no differences in hematologic outcomes between groups were noted. However, in
multivariate logistic regression, infants whose mothers were anemic during
pregnancy were 2.15 times more likely than others to have any laboratory
abnormality (95% confidence interval: 1.14-4.07). Increasing adherence,
regardless of group assignment, was associated with a 0.56 times reduced risk of
any abnormality (95% confidence interval: 0.41-0.76). CONCLUSION: On the basis
of intention-to-treat analysis, multivitamins with iron was not effective in
preventing iron deficiency or anemia in 9-month-old infants. However, effective
prevention and treatment of maternal anemia during pregnancy and giving
multivitamins with or without additional iron during infancy may prove to be
important approaches to the prevention of iron deficiency among high-risk
children. Because of the consequences of iron deficiency and its high prevalence
among low-income infants, additional investigation in these areas is warranted.
-----
Clin Nephrol. 2004 Jun;61(6):392-405.
Once-weekly epoetin alfa for treating the anemia of chronic
kidney disease.
Provenzano R, Garcia-Mayol L, Suchinda P, Von Hartitzsch B, Woollen SB, Zabaneh
R, Fink JC; POWER Study Group.
Department of Nephrology, St. John Hospital and Medical Center, Detroit,
Michigan 48236, USA. provenzano@earthlink.net
BACKGROUND AND AIM: Anemia occurs in approximately 47% of patients with chronic
kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO,
epoetin alfa) has been proven safe and effective for anemia treatment in
patients with CKD using a three times-weekly regimen. The current study was
conducted to evaluate the clinical safety and efficacy of a less frequent dosing
regimen (once weekly) in this population. METHODS: This prospective, multicenter,
open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) <
or = 10 g/dl) CKD patients not on dialysis. Epoetin alfa 10,000 U was
administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once
weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl.
Safety and efficacy were assessed by changes in health-related quality of life
(Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)),
changes in hematologic parameters and transfusion utilization, and incidence and
severity of adverse events. RESULTS: 1,338 patients were evaluable for efficacy.
Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study
completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of
patients responded to once-weekly dosing, exhibiting an increase in Hb level of
> or = 1 g/dl from baseline. The percentage of patients that required
transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p <
0.0001). All quality-of-life parameters improved significantly from baseline (p
< 0.0001). Mean LASA scores for energy, activity and overall quality of life
increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%)
and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically
significant improvements (p < 0.0001). Hb change was a strong predictor for all
5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly
epoetin alfa was well tolerated, similar to that reported with three
times-weekly dosing. CONCLUSION: Once-weekly epoetin alfa therapy is safe and
effective for treating anemia in patients with CKD not on dialysis, and is
associated with significant improvements in functional status and quality of
life.
-----
Pharmacotherapy. 2004 Jun;24(6):757-67.
Anemia management in heart failure: a thick review of thin data.
McBride BF, White CM.
Hartford Hospital Drug Information Center, Hartford, Connecticut 06102-5037,
USA.
Heart failure is defined as the inability of the heart to pump blood at an
amount sufficient to meet the metabolic needs of the body. In heart failure, the
inability to meet the body's metabolic needs is based on hemodynamic derangement
and suboptimal oxygen-carrying capacity of the blood itself. Current
pharmacologic therapy attempts to improve survival and reduce symptomatology by
optimizing hemodynamics to increase oxygen delivery, but does not address
oxygen-carrying capacity. Unfortunately, there is a high prevalence of anemia in
patients with heart failure, which compromises oxygen-carrying capacity, is an
independent predictor of mortality, and may be caused in part by pharmacologic
agents that confer morbidity and mortality benefits in this population.
Recombinant human erythropoietin supplementation improves the functional
capacity of the failing myocardium, reverses and antagonizes the detrimental
remodeling induced by autoimmune activity, and may reduce mortality and
morbidity among patients receiving maximal pharmacologic therapy for heart
failure. However, limited clinical data prohibit widespread recommendations for
its use in patients with heart failure.
-----
Wei Sheng Yan Jiu. 2004 May;33(3):334-6.
[Effect of complementary food supplements on anemia in infant and
young children]
[Article in Chinese]
Wang Y, Chen C, Jia M, Fang J.
National Center for Public Health Surveillance and Information Services, Chinese
Center for Disease Control and Prevention, Beijing 100050, China.
OBJECTIVE: To investigate the effect of complementary food supplements with
protein and multi-micronutrients on hemoglobin and anemia in infant and young
children. METHODS: In 5 poor county of Gansu province, children aged 4-12 months
were enrolled and divided into two groups, protein and micronutrient were
supplemented in Formula I group, all children were observed until they were 24
months old. Every 6 months, a massive dose of Vitamin A was supplemented to all
children, hemoglobin tests were done at the same time. RESULTS: At baseline
survey, there are no differences in hemoglobin and prevalence of anemia between
two groups. During the follow-up of 12 months supplementation, Hemoglobin
increase of the Formula I group is significantly higher than Formula II group(P
< 0.0005), prevalence of anemia reduce obviously and there is statistically
different between the two groups. Hemoglobin increase of the two groups are
significantly different until all children are 24 months old(P = 0.006).
CONCLUSION: Supplemented micronutrient and large-dose Vitamin A can increase
hemoglobin and decrease prevalence of anemia in infant and young children.
-----
Pediatr Hematol Oncol. 2004;21(5):403-410.
Safety Profiles of Fe(2+) and Fe(3+) Oral Preparations in the
Treatment of Iron Deficiency Anemia in Children.
Kavakli K, Yilmaz D, cEtinkaya B, Balkan C, SOzmen EY, Sagin FG.
Department of Pediatric Hematology, Ege University Faculty of Medicine, Izmir,
Turkey.
The major purpose of this study was to compare the oxidant-related toxicities of
the different oral iron preparations in children with iron deficiency anemia
(IDA); the second aim was to investigate the side effects of iron preparations.
Seventy-two children with IDA were randomly included in the Fe(2+) group (n =
39) or the Fe(3+) group (n = 33). Some oxidizable substrates (erythrocytes
malondialdehyde (MDA), urine 8-isoprostane, and basal and Cu-stimulated-oxidized
LDL and antioxidant enzyme (superoxide dismutase (SOD), catalase and glutathione
peroxidase) activities were evaluated at the beginning and at the 1st, 3rd, and
6th months of therapy. Side effects due to medication were recorded. While at
the end of the 1st month SOD levels were significantly increased in Fe(3+)
group, at the 6th month evaluation, basal-oxidized LDL levels were significantly
increased in the Fe(3+) group, as was urine 8-isoprostane in the Fe(2+) group.
No other difference was found between two groups. In conclusion, there were
minimal differences between children treated with ferric or ferrous iron in
antioxidant system activities, the status of oxidizable substrates, and clinical
toxicities.
-----
Wien Med Wochenschr. 2004 May;154(9-10):226-34.
Supportive treatment for anemic cancer patients.
Pohl GM, Ludwig H.
Ist Department of Medicine and Medical Oncology, Wilhelminenspital, Vienna,
Austria.
Anemia in cancer patients is frequent but often underestimated. Anemia affects
the health-related quality of life and impacts prognosis and outcome of therapy.
Treatment options include the administration of hematopoietic growth factors and
red blood cell transfusions. Blood transfusions result in rapid but often
transient improvement of anemia. Administration of epoetin or darbepoetin alfa
increases hemoglobin levels, decreases blood transfusions, and improves quality
of life in patients with cancer. Presently, trials investigate whether treatment
of anemic cancer patients with erythropoietin impacts on outcome of chemo-
and/or radiotherapy and on overall survival. Oncologists must be aware of the
clinical relevance of anemia and offer adequate treatment options to their
patients. Supportive treatment of anemic cancer patients presenting
anemia-related symptoms should be performed to reduce symptoms in cancer
patients and optimize outcome to anticancer therapy.
-----
Clin Nephrol. 2004 May;61 Suppl 1:S10-3.
The importance of exercise training in predialysis patients with
chronic kidney disease.
Clyne N.
Department of Medicine, Sodertalje Hospital, Sodertalje, Sweden. Naomi.Clyne@sts.sll.se
Patients with chronic renal failure show a decline in maximal exercise capacity
and muscle strength as renal function decreases. Renal anemia, skeletal muscle
dysfunction, tiredness and increasing inactivity are the major causes of this
deterioration in predialysis patients. Exercise training improves maximal
exercise capacity, muscle strength and endurance in young, middle-aged and
elderly predialysis patients. It has a positive effect on muscle catabolism and
counteracts weight loss and malnutrition. Moreover, exercise training has
positive effects on functional capacity and health-related quality of life.
However, early referral to a nephrologist and multiprofessional teamwork in the
care of predialysis patients is essential in order to implement comprehensive
predialysis care and exercise training successfully.
-----
Rev Panam Salud Publica. 2004 May;15(5):313-9.
[The effectiveness of three regimens using ferrous sulfate to
treat anemia in pregnant women]
[Article in Spanish]
de Souza AI, Batista Filho M, Ferreira LO, Figueiroa JN.
Instituto Materno Infantil de Pernambuco, Departamento de Pesquisas, Rua dos
Coelhos 300, Boa Vista, CEP 50070-550, Recife, PE, Brasil. arianii@terra.com.br
OBJECTIVE: To evaluate the effectiveness of three regimens employing ferrous
sulfate to treat pregnant women with anemia. METHODS: The study was carried out
at the Women's Health Center of the Pernambuco Institute of Maternal and Child
Health in the city of Recife, Pernambuco, Brazil, from May 2000 to December
2001. A randomized clinical trial with blinded laboratory analysis was
conducted. Iron (60 mg) was administered as 300-mg ferrous sulfate tablets. The
women were allocated to three treatment groups, according to the frequency of
ingesting the tablets: once a week (48 women), twice a week (53 women), and once
a day (49 women). The groups were compared for the values for hemoglobin (Hb)
concentration, mean corpuscular volume, and ferritin before and after the
treatment. RESULTS: Before the intervention, the groups were homogeneous. They
had the following mean (+/- standard deviation) concentrations of hemoglobin:
10.2 +/- 0.5 g/dL for the group receiving iron once a week, 10.2 +/- 0.6 g/dL
for the group receiving iron twice a week, and 10.1 +/- 0.6 g/dL for the group
receiving iron once a day. The means of corpuscular volume were, respectively:
88.5 +/- 5.0 fL, 87.6 +/- 5.9 fL, and 88.7 +/- 5.1 fL. The respective medians
for ferritin were 30.2 ng/mL, 37.1 ng/mL, and 52.9 ng/mL. The cure rate (Hb > 11
g/dL) was 27% in the patients treated once a week, 34% in those treated twice a
week, and 47% in the women treated daily. Treatment failure (hemoglobin < 10 g/dL)
was seen in 41.6%, 13.2%, and 2.0% of the patients in the respective groups.
Interruption of treatment due to diarrhea or epigastric pain occurred only among
the patients treated daily. CONCLUSION: The regimen with iron administered daily
is still the best option for treating anemia. However, treatment with ferrous
sulfate administered twice a week is an alternative for patients who are unable
to adhere to daily treatment.
-----
Crit Care. 2004;8 Suppl 2:S45-8. Epub 2004 Jun 14.
Preoperative recombinant human erythropoietin in anemic surgical
patients.
Monk TG.
Professor, Department of Anesthesiology, Duke University Medical Center, Durham,
North Carolina, USA. Terri.Monk@duke.edu
Preoperative anemia in a surgical patient predisposes to poor outcomes and
allogeneic blood transfusions. As an alternative to transfusions, pharmacologic
management of preoperative anemia with recombinant human erythropoietin (rHuEPO)
has been well studied in many different types of surgery. rHuEPO, when used
alone or in combination with preoperative autologous blood donation before
elective surgery, stimulates erythropoiesis and helps to avoid or reduce the
need for allogeneic blood transfusions. The clinical evidence on preoperative
use of rHuEPO in orthopedic, cardiac, and cancer surgery, as well as in
bloodless surgery, is reviewed.
-----
Crit Care. 2004;8 Suppl 2:S42-4. Epub 2004 Jun 14.
Anemia and blood transfusion in the critically ill patient: role
of erythropoietin.
Corwin HL.
Professor of Medicine and Anesthesiology, Dartmouth Medical School; Section
Chief, Critical Care Medicine; Medical Director, Intensive Care Unit,
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. Howard.L.Corwin@Hitchcock.org
Critically ill patients receive an extraordinarily large number of blood
transfusions. Between 40% and 50% of all patients admitted to intensive care
units receive at least 1 red blood cell (RBC) unit during their stay, and the
average is close to 5 RBC units. RBC transfusion is not risk free. There is
little evidence that 'routine' transfusion of stored allogeneic RBCs is
beneficial to critically ill patients. The efficacy of perioperative recombinant
human erythropoietin (rHuEPO) has been demonstrated in a variety of elective
surgical settings. Similarly, in critically ill patients with multiple organ
failure, rHuEPO therapy will also stimulate erythropoiesis. In a randomized,
placebo-controlled trial, therapy with rHuEPO resulted in a significant
reduction in RBC transfusions. Despite receiving fewer RBC transfusions,
patients in the rHuEPO group had a significantly greater increase in hematocrit.
Strategies to increase the production of RBCs are complementary to other
approaches to reduce blood loss in the intensive care unit, and they decrease
the transfusion threshold in the management of all critically ill patients.
-----
Arch Intern Med. 2004 Feb 9;164(3):262-76.
Epoetin alfa. Clinical evolution of a pleiotropic
cytokine.
Henry DH, Bowers P, Romano MT, Provenzano R.
Pennsylvania Hospital, Joan Karnell Cancer Center, Philadelphia,
PA 19106, USA. dhhenry@juno.com
Recombinant human erythropoietin (epoetin alfa) has been used
in clinical settings for more than a decade. Its indications have
expanded considerably from its original use as hormone therapy
in the treatment of anemia in adults with chronic kidney disease.
Since the introduction of epoetin alfa, a greater understanding
of anemia pathophysiology and the interactions of erythropoietin,
iron, and erythropoiesis has been elucidated. Anemia is now independently
associated with increased mortality and disease progression. Potential
survival benefits associated with correction of anemia in various
patient populations are leading to consideration of earlier, more
aggressive treatment of mild to moderate anemia with epoetin alfa.
Moreover, this agent's therapeutic use may extend beyond currently
accepted roles. Epoetin alfa is undergoing evaluation with promising
results in a variety of new clinical settings, including anemia
associated with congestive heart failure, ribavirin-interferon
alfa treatment of hepatitis C virus infection, and critical illness.
Preclinical studies also have established erythropoietin and its
recombinant equivalent to be a pleiotropic cytokine with antiapoptotic
activity and neuroprotective actions in the central nervous system.
The therapeutic potential of epoetin alfa appears yet to be fully
realized.
-----
J Bone Joint Surg Br. 2004 Jan;86(1):31-3.
Treatment of anaemia after joint replacement.
A double-blind, randomised, controlled trial of ferrous sulphate
versus placebo.
Sutton PM, Cresswell T, Livesey JP, Speed K, Bagga T.
Diana, Princess of Wales Hospital, Grimsby, North Lincolnshire,
England, UK.
After total hip and knee replacement arthroplasty, patients
may become anaemic and may be prescribed oral iron. There is,
however, no published evidence that this is of benefit when used
postoperatively. We treated 72 patients who were anaemic after
primary total hip and knee arthroplasty by randomly allocating
them to receive six weeks of either oral ferrous sulphate (35
patients) or a placebo (37 patients). Both groups of patients
were similar in all aspects except for the treatment given. There
was no statistically significant difference in the change of haemoglobin
levels between the two groups. We therefore believe that the prescription
of iron to all anaemic patients post-operatively should be avoided.
The level of serum ferritin should be monitored at preoperative
assessment.
-----
JAMA 2003 Mar 5;289(9):1130-5
Antithymocyte globulin and cyclosporine for severe
aplastic anemia: association between hematologic response and
long-term outcome.
Rosenfeld S, Follmann D, Nunez O, Young NS.
Hematology Branch, Bldg 10, National Heart, Lung, and Blood Institute,
Bethesda, Md, USA.
CONTEXT: In most patients, aplastic anemia results from T-cell-mediated
immune destruction of bone marrow. Aplastic anemia can be effectively
treated by stem cell transplantation or immunosuppression. OBJECTIVE:
To assess long-term outcomes after immunosuppressive therapy.
DESIGN, SETTING, AND PATIENTS: Cohort of 122 patients (31 were
< or =18 years and 91 were >18 years) with severe aplastic
anemia, as determined by bone marrow cellularity and blood cell
count criteria, were enrolled in a single-arm interventional research
protocol from 1991 to 1998 at a federal government research hospital.
INTERVENTIONS: A dose of 40 mg/kg per day of antithymocyte globulin
administered for 4 days, 10 to 12 mg/kg per day of cyclosporine
for 6 months (adjusted for blood levels), and a short course of
corticosteroids (1 mg/d of methylprednisolone for about 2 weeks).
MAIN OUTCOME MEASURES: Survival, improvement of pancytopenia and
transfusion-independence, relapse, and evolution to other hematologic
diseases. RESULTS: Response rates were 60% at 3 months after initiation
of treatment, 61% at 6 months, and 58% at 1 year. The blood cell
counts of patients who responded no longer satisfied severity
criteria and they were transfusion-independent. Overall actuarial
survival at 7 years was 55%. Survival was associated with early
satisfaction of response criteria (86% vs 40% at 5 years; P<.001)
and by blood counts at 3 months (reticulocyte count or platelet
count of >50 x 10(3)/ microL predicted survival at 5 years
of 90% [64/71] vs 42% [12/34] for patients with less robust recovery
[P<.001 by log-rank test]). There were no deaths among responders
more than 3 years after treatment. Relapse was common, but severe
pancytopenia usually did not recur. Relapse did not influence
survival. Thirteen patients showed evolution to other hematologic
diseases, including monosomy 7. CONCLUSIONS: Approximately half
of patients with severe aplastic anemia treated with antithymocyte
globulin and cyclosporine have durable recovery and excellent
long-term survival. These outcomes were related to the quality
of hematologic recovery.
-----
Crit Care Nurse 2002 Dec;Suppl:1-12; discussion 12-4; quiz
15-6
Understanding and managing anemia in critically
ill patients.
Pearl RG, Pohlman A.
Department of Anesthesia, Stanford University School of Medicine,
Stanford, Calif., USA.
Although anemia is apparently tolerated in most patients, particularly
those who are relatively healthy, the ICU population must be thought
of differently. Anemia in the ICU may be due to acute blood loss,
phlebotomy, or to the presence of inflammatory disease. The anemia
in critically ill patients resembles anemia of chronic disease,
which is believed to result from a poor endogenous erythropoietin
response or erythropoietin deficiency. The risks of blood transfusions
are many and ICU patients may not tolerate infusions of older,
stored blood. Nonetheless, hemoglobin levels at or above 100 g/L
may be important for oxygen delivery to vital organs, especially
in critically ill patients with increased oxygen demands. The
appropriate transfusion trigger for critically ill patients in
this setting remains unknown. Blood transfusions in the ICU may
not improve outcomes, and numerous studies have been published
to suggest the contrary, that transfusions may actually worsen
patients' outcomes in certain ICU settings. Recombinant human
erythropoietin (rHuEPO, epoetin alfa) has been shown to reduce
transfusion needs and increase hemoglobin levels in multiple settings
and now, it appears to also do so in the ICU.
-----
Nefrologia 2002;22(6):555-63
[Anemia management in haemodialysis. EuCliD database
in Spain]
[Article in Spanish]
Aviles B, Coronel F, Perez-Garcia R, Marcelli D, Orlandini G,
Ayala JA, Rentero R.
ICN-Unidad Nefrologica Moncloa Lucio del Valle, 2 28003 Madrid.
avilesbb@hotmail.com
We present the results on Anaemia Management in Fresenius Medical
Care Spain dialysis centres as reported by EuCliD (European Clinical
Database), evaluating a population of 4,426 patients treated in
Spain during the year 2001. To analyse the erythropoietin dose
and the haemoglobin levels we divided the population in two groups
according to the time with dialysis treatment: patients treated
less than six months and patients between six months, and four
years on therapy. We compared our results with the evidence based
recommendations Guidelines: the European Best Practice Guidelines
(EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We
also compared our results with those presented by the ESAM2 on
2,618 patients on dialysis in Spain carried out in the second
half of the year 2000. We observed that 70% of the population
reaches an haemoglobin value higher that 11 g/dl, with a mean
erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n =
3,700; SD 74.9). However, for those patients on treatment for
less than six months, the mean Haemoglobin only reaches 10.65
g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously
in 70.2% of the patients. About the iron therapy, 86% of the patients
received iron treatment and the administration route was intravenous
in 93% of the population. The ferritin levels were below 100 micrograms/dl
in 10% of the patients and 26.4% showed a transferrin saturation
index (TSAT) below 20%. The erythropoieting resistance index (ERI),
as rHu-EPO/haemoglobin, has been used to evaluate the response
to rHu-Epo, according to different variables. It was observed
that the following factors lead to a higher rHu-EPO resistance:
intravenous rHu-EPO as administration route, the presence of hypoalbuminemia,
increase of protein C reactive, Transferrin saturation below 20%
and starting dialysis during the last six months.
--
Zhongguo Shi Yan Xue Ye Xue Za Zhi 2002 Feb;10(1):44-6
[Correlation of bone marrow stromal function in
vitro with efficacy of anisodamine therapy
for aplastic anemia]
[Article in Chinese]
Liu J, Ji SQ, Wang HX, Chen HR, Xue M, Zhu L, Yan HM.
Department of Hematology, The General Hospital of Air Force, Beijing
100036, China.
To observe normal bone marrow stromal function for supporting
hematopoiesis and realize the correlation of bone marrow stromal
function in patients with aplastic anemia (AA) and anisodamine
therapy, normal human marrow CFU-GM was assayed on bone marrow
stromal layer (SL) formed on week 3 culture, and the CFU-GM without
SL as a control (100%). Results showed that the production of
CFU-GM on the normal SL was significantly higher than that of
the control. The production of CFU-GM on the SL of 4 AA patients,
who responded to anisodamine, was < 80% of the control, and
when 2 of them were reexamined for stromal function after treatment,
the number of CFU-GM on SL rose up to 168.8% and 249.2% from 38.7%
and 39.7% of the control respectively. While in the rest 6 patients,
the number of CFU-GM was > 80% of the control, only one patient
was improved by anisodamine therapy. So, normal bone marrow stromal
layer can obviously support the growth of granulocyte/macrophage
progenitor cells. Anisodamine therapy could be an effective agents
for aplastic anemia with stromal dysfunction
-----
Br J Haematol 2002 Dec;119(4):1075-82
Results and follow-up of a phase III randomized
study of recombinant human-granulocyte stimulating factor as support
for immunosuppressive therapy in patients with severe aplastic
anaemia.
Gluckman E, Rokicka-Milewska R, Hann I, Nikiforakis E, Tavakoli
F, Cohen-Scali S, Bacigalupo A; European Group for Blood and Marrow
Transplantation Working Party for Severe Aplastic Anemia.
Hospital Saint-Louis, Paris, France. eliane.gluckman@sls.ap-hop-paris.fr
In patients with idiopathic severe aplastic anaemia who are
treated with immunosuppressive agents to combat T lymphocyte-mediated
destruction of haematopoietic progenitor cells, neutropenia is
a major cause of infections and toxicity. Evidence from preliminary
studies suggests that recombinant human glycosylated granulocyte
colony-stimulating factor (lenograstim) increases the number and
functionality of neutrophils in patients with severe aplastic
anaemia. This randomized, parallel-group, multicentre study was
conducted to evaluate the efficacy and safety of subcutaneous
lenograstim during the first 12 weeks of standard immunosuppressive
therapy in 102 patients with de novo severe aplastic anaemia.
The addition of lenograstim to standard therapy resulted in an
increase in the proportion of patients showing complete neutrophil
response (83.0%vs 44.9%; P < 0.0001). This was seen even among
patients with very severe aplastic anaemia (69.2%vs 31.6%; P =
0.012). In patients receiving lenograstim, median time to complete
neutrophil response was shorter (6.3 vs 16.1 weeks; P = 0.0001)
and mean duration of first neutrophil response was longer (P =
0.0248) than in the control group. At a median follow-up of 5
years, no difference was observed between the groups in term of
survival, haematological response and occurrence of secondary
leukaemia (one patient in each group). We conclude that lenograstim
support of immunosuppressive therapy might be used for patients
with severe aplastic anaemia as it significantly enhances neutrophil
recovery but does not modify the overall response and survival.
-----
JAMA 2002 Dec 11;288(22):2827-35
Comment in: JAMA. 2002 Dec 11;288(22):2884-6.
Efficacy of recombinant human erythropoietin in
critically ill patients: a randomized controlled trial.
Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Shapiro MJ,
Corwin MJ, Colton T; EPO Critical Care Trials Group.
Critical Care Medicine, Dartmouth-Hitchcock Medical Center, One
Medical Center Drive, Lebanon, NH 03756, USA. howard.l.corwin@hitchcock.org
CONTEXT: Anemia is common in critically ill patients and results
in a large number of red blood cell (RBC) transfusions. Recent
data have raised the concern that RBC transfusions may be associated
with worse clinical outcomes in some patients. OBJECTIVE: To assess
the efficacy in critically ill patients of a weekly dosing schedule
of recombinant human erythropoietin (rHuEPO) to decrease the occurrence
of RBC transfusion. DESIGN: A prospective, randomized, double-blind,
placebo-controlled, multicenter trial conducted between December
1998 and June 2001. SETTING: A medical, surgical, or a medical/surgical
intensive care unit (ICU) in each of 65 participating institutions
in the United States. PATIENTS: A total of 1302 patients who had
been in the ICU for 2 days and were expected to be in the ICU
at least 2 more days and who met eligibility criteria were enrolled
in the study; 650 patients were randomized to rHuEPO and 652 to
placebo. INTERVENTION: Study drug (40 000 units of rHuEPO) or
placebo was administered by subcutaneous injection on ICU day
3 and continued weekly for patients who remained in the hospital,
for a total of 3 doses. Patients in the ICU on study day 21 received
a fourth dose. MAIN OUTCOME MEASURES: The primary efficacy end
point was transfusion independence, assessed by comparing the
percentage of patients in each treatment group who received any
RBC transfusion between study days 1 and 28. Secondary efficacy
end points identified prospectively included cumulative RBC units
transfused per patient through study day 28; cumulative mortality
through study day 28; change in hemoglobin from baseline; and
time to first transfusion or death. RESULTS: Patients receiving
rHuEPO were less likely to undergo transfusion (60.4% placebo
vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval
[CI], 0.54-0.83). There was a 19% reduction in the total units
of RBCs transfused in the rHuEPO group (1963 units for placebo
vs 1590 units for rHuEPO) and reduction in RBC units transfused
per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83;
P =.04). Increase in hemoglobin from baseline to study end was
greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94
[1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for
placebo) and adverse clinical events were not significantly different.
CONCLUSIONS: In critically ill patients, weekly administration
of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and
increases hemoglobin. Further study is needed to determine whether
this reduction in RBC transfusion results in improved clinical
outcomes.
-----
Am J Kidney Dis 2002 Dec;40(6):1153-61
Anemia treatment in the pre-ESRD period and associated
mortality in elderly patients.
Xue JL, St Peter WL, Ebben JP, Everson SE, Collins AJ.
Nephrology Analytical Services, Minneapolis, MN, USA.
BACKGROUND: Anemia is a common complication of advancing chronic
kidney disease, yet little is known about the consistency of anemia
treatment before end-stage renal disease (ESRD) and mortality
on dialysis therapy. METHODS: We studied 89,193 incident Medicare
patients with ESRD in 1995 to 1997 aged 67 plus years with claims
2 years before their dialysis therapy initiation. Patients were
classified as follows: no epoetin, 25% or less (least consistent),
greater than 25% to 50%, greater than 50% to 75%, and greater
than 75% (most consistent) epoetin treatment in the available
months from the first pre-ESRD epoetin dose to the first ESRD
service date. Cox regression modeled the risk for 1-year death
in the post-ESRD period, adjusting for age, sex, race, diabetic
status, albumin level, and incidence year. RESULTS: Sixty percent
of patients had hematocrits less than 30% at ESRD initiation,
yet only 15.6% (N = 13,877) had epoetin claims before ESRD. The
most consistent epoetin treatment group had hematocrits increase
from 27.5% to 30.8% (P < 0.0001) by month 4 of treatment. Patients
with the most consistent epoetin treatment had a greater mean
hematocrit (29.2% +/- 0.11%; P < 0.0001) and albumin level
(3.31 +/- 0.01 g/dL [33.1 g/L]) at initiation than those with
the least consistent treatment (28.1% +/- 0.10% and 3.21 +/- 0.01
g/dL [32.1 g/L], respectively). The relative risk for death in
patients with the least consistent versus the most consistent
(the reference) epoetin treatment was 1.460 (95% CI, 1.245 to
1.713; P < 0.0001) 1 year after the first ESRD service date.
CONCLUSION: Elderly patients with consistent pre-ESRD epoetin
treatment had lower risks for death in the first year of dialysis
therapy after ESRD initiation. Copyright 2002 by the National
Kidney Foundation, Inc.
-----
J Nephrol 2002 Sep-Oct;15(5):558-64
Effects of a vitamin E-bonded membrane and of
glutathione on anemia and erythropoietin requirements in hemodialysis
patients.
Usberti M, Gerardi G, Micheli A, Tira P, Bufano G, Gaggia P, Movilli
E, Cancarini GC, De Marinis S, D'Avolio G, Broccoli R, Manganoni
A, Albertin A, Di Lorenzo D.
Nephrology and Dialysis Service, Manerbio Hospital, Brescia, Italy.
mario.usberti@aod.it
BACKGROUND: The oxidative damage of RBC membranes in hemodialysis
(HD) patients increases red blood cell (RBC) susceptibility to
hemolysis and impairs cell survival. Reduction of the oxidative
stress might lead to better control of anemia and reduction of
the erythropoietin (rhEPO) dose. METHODS: We studied 38 stable
HD patients, given a mean dose of rhEPO of 104+/-65 U/kg BW/week,
at baseline and during antioxidant treatment with either a full
or a 50% dose of EPO. Antioxidant treatment involved the combined
use of glutathione, GSH (1200 mg i.v. at the end of each dialysis
session) and a vitamin E-bonded HD membrane, CL-E. RBC and reticulocyte
counts were done monthly. RBC survival (51Cr T/2) was assayed
in 18 patients before and after the end of the study. Oxidative
status was determined in 10 patients by measuring plasma concentrations
of malondyhaldeide-4-hydroxynonenal (MDA-4HNE), reactive oxygen
molecular species (ROMs), and oxydized-LDL (oxLDL) as indices
of oxidative stress, alpha-tocopherol and total thiols as single
antioxidants, and TAS as a marker of total antioxidant plasma
activity. RESULTS: Antioxidant treatment significantly reduced
the high basal plasma concentrations of MDA4HNE and oxLDL, and
significantly increased those of alpha-tocopherol, whereas TAS
and thiols were unmodified. These changes lasted after the reduction
of EPO. Anemia significantly improved with treatment, due to a
significant increase in RBC survival. A close direct linear relationship
was detected between plasma levels of vitamin E and hemoglobin.
CONCLUSIONS: Adequate control of oxidative stress achieves better
control of anemia in HD patients. Since several antioxidant systems
are impaired in uremia, the combined use of the CL-E membrane
and GSH seems to be the best antioxidant therapy so far, with
significant saving of the rhEPO dose.
-----
Nutr Clin Care 2002 Sep-Oct;5(5):220-4
Evaluation and treatment of iron deficiency in
adults.
Ross EM.
Tufts University Schools of Medicine and Nutrition, Boston, MA,
USA. eross@lifespan.org
Iron deficiency is prevalent in populations seen in primary
practices. It is easily evaluated and treated, but often undiagnosed.
Iron deficiency can lead not only to anemia but to decreased work
capacity, abnormal neurotransmitter function, and altered immunologic
and inflammatory defenses. Risk for iron deficiency is a function
of iron loss, iron intake, iron absorption, and physiologic demands.
Women of child-bearing age are at especially high risk for iron
deficiency due to ongoing menstrual blood losses. This article
presents and describes a simple algorithm incorporating dietary
considerations for evaluation and treatment of iron deficiency
in primary care settings.
-----
Eur J Haematol 2002 Oct;69(4):236-42
Possible ameliorative effect of taurine in the
treatment of iron-deficiency anaemia in female university students
of Gaza, Palestine.
Sirdah MM, El-Agouza IM, Abu Shahla AN.
Biology Department, Faculty of Science, Al Azhar University, PO
Box 1277 Gaza, Gaza Strip, Palestine. msirdah@hotmail.com
The aim of the study was to evaluate the haematological effects
of adding the antioxidant taurine to iron sulfate in the treatment
of iron-deficiency anaemia (IDA). A sample of 730 students from
Al-Azhar University, Gaza, in Palestine underwent screening with
complete blood counts and serum samples. In subjects with microcytosis/hypochromasia,
Alpha2 delta2 (HbA2) and serum concentrations of iron, total iron
binding capacity (TIBC), ferritin and taurine were determined.
Samples from 17 normocytic, normochromic, and non-anaemic subjects
were used as baseline controls. At base-line, 81 of the 730 subjects
(11.1%) had microcytosis/hypochromasia, 26 (3.6%) were diagnosed
as beta-thalassemia carriers, none of which was iron deficient.
Four subjects had microcytosis of unknown cause. Fifty-one subjects
(all females) had iron-deficiency anaemia and were included in
the therapeutic study, which lasted for 20 wk. They were matched
for Hb into pairs and were treated with oral iron (325 mg of slow-release
iron sulfate). In addition, they were, in a double-blind procedure,
randomised to additional oral taurine (1000 mg d(-1) at a cost
comparable to that of adding ascorbic acid) or placebo. Mean S-taurine
was significantly lower in the IDA subjects than in the controls.
After 20 wk of iron supplementation, both the taurine and placebo
group significantly improved their Hb concentrations and normalised
the markers of iron deficiency. Apart from the expected, albeit
in this study mild side-effects of oral iron, no significant side-effects
were noted. In the taurine group, there was a statistically significant
additive positive change from the baseline values on Hb (2.67
+/- 1.24 g dL(-1)), red blood cell (RBC) count [(0.57 +/- 0.25)
x 1012 L(-1)] and serum ferritin (30.33 +/- 17.99 microg L(-1))
as compared to placebo group values, which were 1.80 +/- 1.10
g dL-1, (0.39 +/- 0.36) x 1012 L(-1), and 20.11 +/- 7.34 microg
L(-1), respectively. Oral taurine appears to increase the effectiveness
of oral iron in the treatment of IDA, and has no significant side-effects.
This merits further cost-benefit and clinical analyses.
-----
Int J Hematol 2002 Oct;76(3):244-50
Long-term follow-up of patients with aplastic
anemia and refractory anemia responding to combination therapy
with recombinant human granulocyte colony-stimulating factor and
erythropoietin.
Matsuda A, Kishimoto K, Yoshida K, Yagasaki F, Ito Y, Sakata T,
Kawai N, Ino H, Hirashima K, Bessho M.
amatsu@saitama-med.ac.jp
In our previous study, approximately 60% of aplastic anemia
(AA) and refractory anemia (RA) patients treated with recombinant
human granulocyte colony-stimulating factor (rhG-CSF) and recombinant
human erythropoietin (rhEpo) showed a multilineage response. In
this study, we analyzed the long-term follow-up of the multilineage
responders (multi-R). In the follow-up analysis of 11 multi-R
(6 AA and 5 RA), 10 patients (5 AA and 5 RA) were evaluable. The
range of time from the start of treatment to the final contact
was 50 to 125 months. Analysis of survival times revealed a significant
difference between multi-R and non-multi-R among AA patients given
this treatment (P = .016). One AA and 1 RA patient among the multi-R
developed acute leukemia. Of 7 living multi-R, 3 AA and 2 RA patients
did not need transfusion at final contact. Four of them maintained
the target hemoglobin concentration of more than 11 g/dL for quality-of-life
benefit. The findings suggested that this result is an important
advantage of this treatment.
©Copyright 1992-date by The Center
for Current Research. The Anemia File is a proprietary compilation
of the Center for Current Research. The information in the File
is solely for your use, and the use of your family, friends, and
doctors. The information is the property of the individual researchers
and institutions that produced it. It is an infringement of copyright
law to attempt to "resell" the information as it is
presented here.
|
