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Procrit and Aranesp for aplastic anemia – pro

admin — Sun, 02 Sep 2012 00:03:04 +0000

Is aranesp considered medically necessary for aplastic anemia?

Erythropoietin levels are elevated in apalstic anemia patients. This raises the probability that additional exogenous erythropoietin may not be effective. However, despite the same concern, erythropoietin is effective in in myelodysplastic syndrome. I reference a Japanese editorial that advocated the use of erythropoietin ( and this would include darbepoetin) for aplastic anemia.

However, there is very little supporting literature and no recommendations that are based on credible studies. Some experts do not support erytropoietin therapy in aplastic anemia. A noted authority, Dr. Jerry L. Spivak said this: “Myelofibrosis, leukemia, and aplastic anemia are other situations where erythropoietin therapy is usually ineffective, and when infection or inflammation is sufficiently severe, the response to erythropoietin will be blunted.”, at http://www.anemia.org/professionals/asktheexpert/treatment.jsp
However, there is very little supporting literature and no recommendations that are based on credible studies. Some experts do not support erytropoietin therapy in aplastic anemia at all, and t, to the extent, that the literature supports it, Procrit has been most commonly used. There is no literature based reason to use Aranesp over Procrit.

MV. . Pavlovic-Kentera Erythropoietin in aplastic anemia Annals Hematology
Volume 39, Number 5 / November, 1979

M Bessho, I Jinnai, A Matsuda, M Saito and K Hirashima
Improvement of anemia by recombinant erythropoietin in patients with myelodysplastic syndromes and aplastic anemia International Journal of Cell Cloning, Vol 8, 445-458,

Phillip Scheinberg et al, How I treat acquired aplastic anemia. Blood. 2012 Aug 9; 120(6): 11851196.

Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan. 172 (2):187-207

Aranesp intravenously – pro

M Levin, MD — Thu, 23 Aug 2012 02:46:56 +0000

Lay Sumamry: Aranesp intravenously works as well as by injection under the skin.

Darebpoietin is FDA approved for sq administration unlike erytrhopoietin. However, there are situations in which IV adminsitration is more convenient for the patient, such as, for example, when there is on onging IV line for another reason. The two most common settings of this kind are the neonates and patients on dyalisis. The treatment of renal anaemia using erythropoiesis stimulating agents (ESAs) [darbepoetin alfa and recombinant human erythropoietin (rHuEPO) alfa or beta] is now a common clinical practice in patients with chronic kidney disease (CKD). There is evidence that both routes of administration result in similar blood levels and effectiveness. This evidence is sufficiently convincing for the pharamcologic standpoint to consider the IV route to be standard of care.

T L Warwood et al, Urinary excretion of darbepoetin after intravenous vs subcutaneous administration to preterm neonates Journal of Perinatology (2006) 26, 636–639.

Fernando Carrera, Lino Oliveira, Pedro Maia, Teresa Mendes and Candido Ferreira The efficacy of intravenous darbepoetin alfa administered once every 2 weeks in chronic kidney disease patients on haemodialysis Nephrology Dialysis Transplantation 2006 21(10):2846-2850

I. C. Macdougall, D. Padhi, and G. Jang
Pharmacology of darbepoetin alfa
Nephrol. Dial. Transplant., June 1, 2007; 22(suppl_4): iv2 – iv9.

Erytropoietin therapy for myelofibrosis – pro

M Levin, MD — Thu, 23 Aug 2012 02:43:24 +0000

Experience with recombinant human erythropoietin (rHuEPO) in the treatment of the anemia secondary to myelofibrosis with myeloid metaplasia (MMM) is limited.There are a number of reports of small numbers of patiens demonstrating responsiveness but also a recent report which presents a picture of non-responsiveness of transfusion dependent myelofibrosis to erythropoietin therapy.
Initial studies failed to show significant improvements in hemoglobin levels upon administration of recombinant erythropoietin (rEpo). However, more recent investigations have demonstrated significant responses and decreased transfusion dependence in anemic patients with CIMF. The rEpo doses employed in those studies were in the range of 300–1,500 U/kg weekly. This finding underscores the current uncertainty about the optimal dose and schedule of rEpo in this disease. It is important to note that many patients with CIMF have normal serum erythropoietin levels, suggesting a potential lack of efficacy of rEpo in this setting [54]. Rodriguez et al. [ showed that a serum erythropoietin level <123 mU/ml was highly predictive of response to rEpo. This was recently corroborated by Cervantes et al. [53] in a study in which rEpo was given at an initial dose of 10,000 U three times per week to 20 patients with CIMF. Nine patients (45%) responded, including four who achieved normal hemoglobin levels. A serum erythropoietin level <125 mU/ml was associated with a favorable response to rEpo in the multivariate analysis. The combination of rEpo and thalidomide may represent a valid approach for patients with advanced CIMF
Future investigation will focus on stratification. Favorable cytogenetic findings was associated with response to erythropoietin therapy in one study.

In summary, there is sufficient evidence that Procrit raises Hb levels in many myelofibrosis patients. How to select patients is not entirely clear yet and at this time, a trial for effectivenesss is standard practice.It is not known whetehr it is a better long – term approach than periodic transfusions

Tsiara S, Kapsali H, Dimos GA, Chaidos A, Stoura M, Bourantas LK, Tzouvara E, Bourantas KL:
Treatment of anemia with recombinant human erythropoietin administration in patients with myelofibrosis, Archives of Hellenic Medicine 20 (3) : 281-285 (May 2003)

S.N. Tsiara, A. Chaidos, L.K. Bourantas, H.D. Kapsali, K.L. BourantasRecombinant Human Erythropoietin for the Treatment of Anaemia in Patients with Chronic Idiopathic Myelofibrosis Heamatoloica Vol. 117, No. 3, 2007

EAuthor Huang, J. Lasho, T.L. Li, C.Y. Pardanani, A.D. Mesa, R.A. Tefferi, A.
rythropoietin Therapy Does Not Benefit Transfusion-Dependent Primary Myelofibrosis Patients and Treatment Response Is Infrequent with a Baseline Hemoglobin Level >or= 10 g/dL
BLOOD 2007, VOL 110; pages 3555

Tefferi A, Lasho TL, Schwager SM et al. The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005;131:320–328

Procrit, Aranesp and G-CSF for myelodysplasia – pro

M Levin, MD — Wed, 20 Jun 2012 20:09:03 +0000

Treatment of anemia with recombinant human erythropoietin (rHuEPO) alone is effective only in a small percentage of MDS patients. A meta-analysis of 205 patients with MDS showed that 16% responded to rHuEPO alone.Patients with a transfusion need of < 2 units per month and a serum erythropoietin concentration of < 500 U/l had a 74% response rate to combined erythropoietin/G-CSF compared to a response rate of 23% and 7% for those patients with a > 2 units per month transfusion need or serum erythropoietin concentration > 500 U/l or both of these risk factors, respectively. Recent randomized, placebo controlled, double-blind clinical trial of erythropoietin was reported in which the rHuEpo treated patients had a median survival of 17 months compared to a median survival of 11 months in the placebo treated patients.

Although FDA has not approved erutropoietin stimulaitng factors for MDS, several supportive guidelines have been published. The first was the Italian Society of Hematology in 2002, updated in 2004. A

The last updateon this topic the 2011 National Comprehensive Cancer Network guideline dedicates significant space too the evaluationand treatment of of MDS-related anemia. For symptomatic anemia, in IPSS low group, treatment is indicated by the level of endogenous EPO. If EPO < 500U/L, the treatment of choice is EPO-alpha, 40,000–60,000 U, 1–3 times weekly subcutaneously (s.c.), or darbepoetin, 150–300 μg weekly s.c. In cases of the presence of ringed sideroblasts or an absence of response, the addition of G-CSF, 1–2 μg/kg 1–3 times per week should be considered, as well as therapy with immunosuppressive or hypomethylating agents when endogenous EPO levels are >500 U/L.

Similar guidelines were published by the American Society of Hematology and the American Society of Clinical Oncology. Some guidelines, for example NCCN, recommend erytrhopoietin in IPSS Low disease and with erytropoietin levels below 500. The NCCN 2007 version of the guidelines added darbepoetin alfa (Aranesp®, Amgen) as a recommendation for anemic patients with low-intermediate risk MDS.

There are intriguing reports of MDS patients responding to long-acting darbepoetin (DAR) after being refractory to primary treatment with EPO. However, a recent meta-analysis compared treatment with EPO-α (n=589; 9 studies) versus DAR (n=389; 8 studies) and concluded that the response rates for both drugs were highly similar (58% and 59%, respectively, P=0.82) when assessed using unified response criteria as defined by the International Working Group (IWG) in 2000. Finally, the addition of G-CSF significantly enhanced the response rate compared with using EPO alone, as demonstrated in two randomized trials.

Jädersten M et al, Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol 2008;26:3607-3613

Musto P, et al, . Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes. Leuk Res 2010;34:981-985.

Alessandrino EP et al, Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica 2002;87:1286-1306.

Santini V,PE et al, . Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res 2010;34:1576-1588

I. Casadevall, P. Durieux, S. Dubois, F. Hemery, E. Lepage, M.-C. Quarre, G. Damaj, S. Giraudier, A. Guerci, G. Laurent, et al. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial
Blood, July 15, 2004; 104(2): 321 – 327.

Casadevall N, Durieux P, Dubois S, et al. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004;104:321-327.

Balleari E, Rossi E, Clavio M, et al. Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study. Ann Hematol. 2006;85:174-180.

Valeria Santini Clinical Use of Erythropoietic Stimulating Agents in Myelodysplastic Syndromes The Oncologist August 2011 vol. 16 suppl 3 35-42

Uwe Platzbecker, Treatment of MDS. Blood 2019 133:1096-1107