Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants

Abstract

We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.

Concise Review: The Bone Marrow Niche as a Target of Graft Versus Host Disease

“…Drugs that have been approved for stimulating individual hematopoietic lineages except for B and T cells are commercially available and are routinely used beyond HSCT. Even in the context of allogeneic HSCT, the serum levels of erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony‐stimulating factor (G‐CSF) have been demonstrated to correlate inversely with the red blood cell, platelet, and neutrophil counts, respectively, thus reflecting normal physiological behavior . Only EPO levels have been described as inadequate for the anemia observed after MAC .…”

“…Even in the context of allogeneic HSCT, the serum levels of erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony‐stimulating factor (G‐CSF) have been demonstrated to correlate inversely with the red blood cell, platelet, and neutrophil counts, respectively, thus reflecting normal physiological behavior . Only EPO levels have been described as inadequate for the anemia observed after MAC . No clinical trials of erythropoiesis‐stimulating agents (ESAs), TPO‐mimetics, or G‐CSF for GvHD‐associated anemia, thrombopenia, or neutropenia, respectively, have been published.…”

Use of Recombinant Human Erythropoietin Outside the Setting of Uremia

“…Endogenous Epo production is frequently inadequate inChemotherapy-induced anemia † recipients of allogeneic BMT and this may delay erythropoi-Perisurgical setting ‡ etic recovery 161. A pilot study showed that rHuEpo adminis-Acceleration of erythroid repopulation after allogeneic BMT effective.165 In one of the previous studies, rHuEpo appeared…”

Low dose erythropoietin is effective in reducing transfusion requirements following allogeneic HSCT

“…Following autologous transplantation, Epo levels have been shown to remain adequate throughout the post‐transplant course (Bosi et al ., 1991). This appropriate response to anaemia contrasts markedly with the Epo response observed after allogeneic haemopoietic stem cell transplantation (HSCT), where a prolonged period of inappropriately low endogenous Epo levels is seen (Beguin et al ., 1991; Miller et al ., 1992; Baron et al ., 2003).…”