Optimization of recombinant human erythropoietin therapy after allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with prolonged anemia caused by defective erythropoietin (Epo) production. We enrolled 34 recipients of an allogeneic HSCT in three consecutive trials to determine the optimal utilization of recombinant human erythropoietin (rhEpo) therapy in this setting.


METHODS
In the first trial (n = 7), rhEpo 1400 U/kg/week was given from day 1 until a hemoglobin (Hb) level of 10 g/dL was achieved, for a maximum of 60 days. In the second trial, rhEpo 500 U/kg/week was given to achieve Hb levels of 13 to 14 g/dL in 13 anemic patients with fatigue 56 to 1440 days after transplant. In the third trial, rhEpo was scheduled to start on day 35 in 14 patients at a dose of 500 U/kg/week with the aim of achieving Hb levels of 13 to 14 g/dL.


RESULTS
In trial 1, erythroid recovery to 1% reticulocytes and red blood cell transfusion independence were faster, but the number of transfusions was not reduced compared to 10 controls. Responses were brisk in trial 2, with transfusion independence achieved after a median of 1 week in 12 of 13 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 6, 7, 10, and 10 weeks, respectively. Transfusions were significantly reduced in the first month of rhEpo therapy. In trial 3, transfusion independence was obtained after a median of 1 week in 13 of 14 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 3, 4, 6, and 8 weeks, respectively. Transfusions rates were considerably reduced compared to the previous month in the same patients or compared to controls undergoing peripheral blood or marrow transplant without rhEpo.


CONCLUSIONS
Anemia after allogeneic HSCT is exquisitely sensitive to rhEpo. The benefit is minimal when it is given early post-transplant, as used in all trials to date. However, the rate of major response is greater than 90% when rhEpo is started after day 35. These data provide the basis on which to conduct a prospective, randomized, placebo-controlled trial of rhEpo therapy after allogeneic HSCT.
Baron
Frédéric
F
Department of Medicine, Division of Hematology, University of Liège, Liège, Belgium.
Sautois
Brieuc
B
Baudoux
Etienne
E
Matus
Geoffrey
G
Fillet
Georges
G
Beguin
Yves
Y
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D016026:Bone Marrow Transplantation; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D011994:Recombinant Proteins; D013922:Thrombocytosis / Q000628:therapy; D014184:Transplantation, Homologous / Q000502:physiology*
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D016572:Cyclosporine