Darbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation : A prospective multicenter randomized trial
[en] We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 lg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n524), 79% in Arm 2 (n525), and 100% in Arm 3 (n523; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n546) than in Arm 2 (n550; P50.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P< 0.0001), i.v. iron administration (P50.0010), high baseline Hb (P< 0.0001), and low baseline creatinine (P50.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post-transplant. I.v. iron sucrose further improves erythroid recovery.
Disciplines :
Hematology
Author, co-author :
BEGUIN, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Maertens, Johan
DE PRIJCK, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Schots, Rik
Seidel, Laurence ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
BONNET, Christophe ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
HAFRAOUI, Kaoutar ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
WILLEMS, Evelyne ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Vanstraelen, Gaetan
SERVAIS, Sophie ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
JASPERS, Aurélie ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
FILLET, Georges ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
BARON, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Darbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation : A prospective multicenter randomized trial
Publication date :
2013
Journal title :
American Journal of Hematology
ISSN :
0361-8609
eISSN :
1096-8652
Publisher :
Wiley Liss, Inc., New York, United States - New York
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Beguin Y, Baron F, Fillet G. Influence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation. Haematologica 1998;83:1076-1081.
Rizzo JD, Somerfield MR, Hagerty KL, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood 2008;111:25-41.
Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer 2007;43:258-270.
Beguin Y, Oris R, Fillet G. Dynamics of erythropoietic recovery after bone marrow transplantation: Role of marrow proliferative capacity and erythropoietin production in autologous versus allogeneic transplants. Bone Marrow Transplant 1993;11:285-292.
Beguin Y, Clemons GK, Oris R, Fillet G. Circulating erythropoietin levels after bone marrow transplantation: Inappropriate response to anemia in allogeneic transplants. Blood 1991;77:868-873.
Baron F, Frere P, Fillet G, Beguin Y. Recombinant human erythropoietin therapy is very effective after an autologous peripheral blood stem cell transplant when started soon after engraftment. Clin Cancer Res 2003;9:5566-5572.
Pene R, Appelbaum FR, Fisher L, et al. Use of granulocyte-macrophage colony-stimulating factor and erythropoietin in combination after autologous marrow transplantation. Bone Marrow Transplant 1993;11:219-222.
Link H, Boogaerts MA, Fauser AA, et al. A controlled trial of recombinant human erythropoietin after bone marrow transplantation. Blood 1994;84:3327-3335.
Locatelli F, Zecca M, Pedrazzoli P, et al. Use of recombinant human erythropoietin after bone marrow transplantation in pediatric patients with acute leukemia: Effect on erythroid repopulation in autologous versus allogeneic transplants. Bone Marrow Transplant 1994;13:403-410.
Locatelli F, Zecca M, Ponchio L, et al. Pilot trial of combined administration of erythropoietin and granulocyte colony-stimulating factor to children undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 1994;14:929-935.
Vannucchi AM, Bosi A, Ieri A, et al. Combination therapy with G-CSF and erythropoietin after autologous bone marrow transplantation for lymphoid malignancies: A randomized trial. Bone Marrow Transplant 1996;17:527-531.
Cella D. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: A new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 1997;34:13-19.
Beguin Y, Huebers HA, Josephson B, Finch CA. Transferrin receptors in rat plasma. Proc Natl Acad Sci USA 1988;85:637-640.
Baron F, Sautois B, Baudoux E, et al. Optimization of recombinant human erythropoietin therapy after allogeneic hematopoietic stem cell transplantation. Exp Hematol 2002;30:546-554.
Baron F, Fillet G, Beguin Y. Erythropoiesis after nonmyeloablative stem-cell transplantation is not impaired by inadequate erythropoietin production as observed after conventional allogeneic transplantation. Transplantation 2002;74:1692-1696.
Baron F, Frere P, Beguin Y. Once weekly recombinant human erythropoietin therapy is very efficient after allogeneic peripheral blood stem cell transplantation when started soon after engraftment. Haematologica 2003;88:718-720.
Vanstraelen G, Baron F, Frere P, et al. Efficacy of recombinant human erythropoietin therapy started one month after autologous peripheral blood stem cell transplantation. Haematologica 2005;90:1269-1270.
Baron F, Frere P, Fillet G, Beguin Y. Tandem high-dose therapy (HDT) for multiple myeloma: Recombinant human erythropoietin therapy given between first and second HDT allows second peripheral blood stem cell transplantation without red blood cell transfusion. Br J Haematol 2003;123:103-105.
Baron F, Vanstraelen G, Beguin Y. Transfusions after nonmyeloablative or reduced-intensity conditioning regimens. Leukemia 2006;20:2081-2086.
Beguin Y. Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients. Haematologica 2002;87:1209-1221.
Cazzola M, Ponchio L, Pedrotti C, et al. Prediction of response to recombinant human erythropoietin (rHuEpo) in anemia of malignancy. Haematologica 1996;81:434-441.
Pedrazzini A. Erythropoietin and GM-CSF following autologous bone marrow transplantation. Eur J Cancer 1993;29(suppl 2):S15-S17.
Ayash LJ, Elias A, Hunt M, et al. Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation. Br J Haematol 1994;87:153-161.
Chao NJ, Schriber JR, Long GD, et al. A randomized study of erythropoietin and granulocyte colony-stimulating factor (G-CSF) versus placebo and G-CSF for patients with Hodgkin's and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation. Blood 1994;83:2823-2828.
Pierelli L, Scambia G, Menichella G, et al. The combination of erythropoietin and granulocyte colony-stimulating factor increases the rate of haemopoietic recovery with clinical benefit after peripheral blood progenitor cell transplantation. Br J Haematol 1996;92:287-294.
Cazzola M, Guarnone R, Cerani P, et al. Red blood cell precursor mass as an independent determinant of serum erythropoietin level. Blood 1998;91:2139-2145.
Loo M, Beguin Y. The effect of recombinant human erythropoietin on platelet counts is strongly modulated by the adequacy of iron supply. Blood 1999;93:3286-3293.
Auerbach M, Ballard H, Trout JR, et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: A multicenter, open-label, randomized trial. J Clin Oncol 2004;22:1301-1307.
Henry DH, Dahl NV, Auerbach M, et al. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist 2007;12:231-242.
Hedenus M, Birgegard G, Nasman P, et al. Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: A randomized multicenter study. Leukemia 2007;21:627-632.
Pedrazzoli P, Farris A, Del Prete S, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha. J Clin Oncol 2008;26:1619-1625.
Bastit L, Vandebroek A, Altintas S, et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol 2008;26:1611-1618.
Petrelli F, Borgonovo K, Cabiddu M, et al. Addition of iron to erythropoiesis-stimulating agents in cancer patients: A meta-analysis of randomized trials. J Cancer Res Clin Oncol 2012;138:179-187.
Steensma DP, Sloan JA, Dakhil SR, et al. Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy-associated anemia. J Clin Oncol 2011;29:97-105.
Aapro M, Beguin Y, Birgegard G, et al. Too-low iron doses and too many dropouts in negative iron trial? J Clin Oncol 2011;29:e525-e526.
Steensma DP, Sasu BJ, Sloan JA, et al. The relationship between serum hepcidin levels and clinical outcomes in patients with chemotherapy-associated anemia treated in a controlled trial. J Clin Oncol 2011;29(suppl 1):9031.
Auerbach M, Silberstein PT, Webb RT, et al. Darbepoetin alfa 300 or 500 mug once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. Am J Hematol 2010;85:655-663.
Hedenus M, Nasman P, Liwing J. Economic evaluation in Sweden of epoetin beta with intravenous iron supplementation in anaemic patients with lymphoproliferative malignancies not receiving chemotherapy. J Clin Pharm Ther 2008;33:365-374.
Bregman DB, Morris D, Koch TA, et al. Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia. Am J Hematol 2013;88:97-101.
Glaspy J. The impact of epoetin alfa on quality of life during cancer chemotherapy: A fresh look at an old problem. Semin Hematol 1997;34:20-26.
Demetri GD, Kris M, Wade J, et al. Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: Results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 1998;16:3412-3425.
Bohlius J, Schmidlin K, Brillant C, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: A meta-analysis of randomised trials. Lancet 2009;373:1532-1542.
Rizzo JD, Brouwers M, Hurley P, et al. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood 2010;116:4045-4059.
Aapro M, Scherhag A, Burger HU. Effect of treatment with epoetin-beta on survival, tumour progression and thromboembolic events in patients with cancer: An updated meta-analysis of 12 randomised controlled studies including 2301 patients. Br J Cancer 2008;99:14-22.
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