Erythropoiesis after nonmyeloablative stem-cell transplantation is not impaired by inadequate erythropoietin production as observed after conventional allogeneic transplantation

Abstract

Background. It is now well established that after conventional allogeneic hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is impaired because erythropoietin (Epo) production remains inadequate for prolonged periods of time. However, erythropoietic reconstitution after nonmyeloablative SCT (NMSCT) has never been characterized.Methods. Twelve patients received a nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation (TBI) alone (n‫,)6؍‬ 2 Gy TBI and fludarabine (n‫,)3؍‬ or cyclophosphamide and fludarabine (n‫,)3؍‬ followed by transplantation of allogeneic peripheral blood stem cells. Graft-versus-host-disease (GvHD) prophylaxis was carried out with mycophenolate mofetil (from day ؊1 to day 28) plus cyclosporine (from day ؊1 to day 120 or longer in case of chronic GvHD). Erythropoiesis was quantitated by soluble transferrin receptor (sTfR) levels, and the adequacy of Epo production was evaluated by the observed-to-predicted Epo ratio (O/P Epo).Results. Mean sTfR levels decreased following the conditioning regimen but remained well within the normal range throughout the posttransplant period. The O/P Epo ratio presented an initial surge quite similar to that observed after conventional conditioning. Thereafter, the O/P Epo ratio normalized rapidly, and Epo levels remained adequate during the whole observation period. Conclusion.Contrarily to what is observed after myeloablative transplant, Epo levels remained adequate after NMSCT, resulting in normal erythropoiesis. These results suggest that the administration of erythropoietin therapy (rHuEpo) could be less effective after NMSCT than after conventional allogeneic transplant.

Early administration of recombinant erythropoietin improves hemoglobin recovery after reduced intensity conditioned allogeneic stem cell transplantation

“…In this regard, the presence of relatively high and adequate endogenous erythropoietin levels reported after RIC-allo-SCT suggests that rHuEPO might exert its stimulatory effect early after allo-SCT. 26 This is in accordance with the quicker Hb recovery we previously described after RIC allo-SCT as compared to myeloablative, standard allo-SCT. However, one could argue that the detection of adequate levels of endogenous erythropoietin cannot justify the use of rHuEPO in this setting.…”

“…However, one could argue that the detection of adequate levels of endogenous erythropoietin cannot justify the use of rHuEPO in this setting. 26 The latter may be partially true, but we can also hypothesize that the maintenance of erythropoietic progenitor cells early after allo-SCT can be an attractive situation arising from post-graft rHuEPO stimulation. One can also hypothesize that the peripheral blood stem cell source might also contribute to the greater efficiency of EPO in the PBSCT settings, since it has already been shown that PB-derived stem cells contain a larger amount of EPOsusceptible progenitor cells as compared to bone marrowderived stem cells usually described in the older trials.…”

Recombinant human erythropoietin therapy after allogeneic hematopoietic cell transplantation with a nonmyeloablative conditioning regimen: Low donor chimerism predicts for poor response

“…Contrary to conventional allogeneic HCT, NMHCT is not associated with endogenous EPO deficiency [33]. Rather, EPO O/P ratios remain well within the normal range over the whole posttransplant follow-up [33].…”

“…The first 14 NMHCT recipients did not receive rHuEPO (control group) and were previously reported [33]. For the prospective phase II trial, we decided to start rHuEPO on day 30 (EPO group 1, n 5 27), because we had previously shown that this approach was very effective after myeloablative conditioning and transplantation of autologous [20,39] or allogeneic [18] HCT.…”

“…Rather, EPO O/P ratios remain well within the normal range over the whole posttransplant follow-up [33]. However, although both red blood cell (RBC) and platelet transfusion requirements are reduced in NMHCT compared to conventional PBSCT [12,[34][35][36], many NMHCT recipients experience prolonged anemia and many of them still require RBC transfusions [12,34,36].…”