First Report of a Prospective Randomised Controlled Trial of Recombinant Human Erythropoietin after Allogeneic Blood Stem Cell Transplantation.

Recombinant human erythropoietin (rHuEPO) stimulates progenitor cells of erythropoiesis and increases erythrocyte production. This prospective, placebo-controlled, double-blind trial was designed to evaluate the use of erythropoietin versus red blood cell transfusions (RBC) to evade detrimental effects of anaemia during the first weeks after allogeneic peripheral blood stem cell transplantation (alloPBSCT). Between 4/2002 and 4/2004, 52 patients recieved either 10.000 units rHuEPO [Erypho^(R)] 3 times a week subcutaneously or placebo, stratified according to AB0-incompatibility. Applications were started after stem cell transfusion (day +1) and lasted up until in mean day +39.5 [range: 29–50] or until haematocrit (HC) levels reached 0.38. Both groups underwent identical supportive care and RBC transfusion policy. Need for transfusion was defined by HC< 0.27. At time of transplantation, 18 (35%) patients were in remission, and 34 (65%) in advanced stage of their disease. Within the 22 female and 30 male patients (median age: 44.5 years [range:17–64]) 52 % (n=27) received for conditioning treatment a total body irradiation-based regimen, 4% (n=2) high dose treosulfan and cyclophosphamid, and 48 % (n=25) a dose reduced conditioning including fludarabine, busulfan/melphalan and anti-thymocyte globuline, respectively. Thirteen (25 %) patients received transplant from HLA-identical family donors, 26 (50%) from HLA-matched unrelated and 13 (25 %) from mis-matched alternative donors. The two study groups were well balanced regarding age, gender, disease status, graft characteristics, and conditioning regimens. Two patients were excluded from the study due to graft failure on day 21 and one patient refused further treatment on day 37. Eight side effects were observed in the rHuEPO group (3 x local haematoma, 3 x bone/muscle pain, 1 x dizziness, 1 x headache), whereas one was reported in the placebo group (1x headache). No serious adverse event related to study drug was noted. The mean numbers of RBC transfusions were 10.8 ± 5.5 [range: 4–18] with placebo and 9.9 ± 4.2 [range: 6–19] with rHuEPO up to day +50. These effects were identical in the unrelated donor group (n=24) with 11.4 ± 5.7 versus 10.4 ± 4.1, and in the HLA-identical family donor group (n=28) 10.8 ± 5.5 versus 9.4 ± 2.4. Interestingly, in the minor AB0-group (n=15) the rHuEPO arm needed 8.1 ± 3.4 as compared to 12.4 ± 4.2 RBC transfusion in the placebo arm. No differences were observed in the major AB0 group (n=12). Reticulocytes, by similar lab counts on day 0 in both groups, were significantly enhanced on day +30 in the rHuEPO arm. (62.6 ± 18.9 versus 29.3 ± 14.3; p < 0.001). Mean HC on day + 30 was 0.28 ± 0.03, on day + 50 0.33 ± 0.05 in the placebo arm, 0.31 ± 0.03 and 0.36 ± 0.04 in the rHuEPO arm, respectively. Overall survival of the total group after the first 100 days was 49/52 (94,2%).One (3.8%) patient died in placebo-group, and 2 (7.7%) patients in the rHuEPO-group. Further clinical parameters like engraftment, acute graft-versus-host disease (GvHD) and relapse rate were not different between the two treatment groups so far. After alloPBSCT rHuEPO can be given without initial clinical relevant side effects. We conclude that the reconstitution of erythropoiesis seems to be accelerated by early treatment with rHuEPO and reduces number of RBC-transfusions in AB0 minor incompatibility situation after alloPBSCT.