Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia

Little information is available on the evolution of erythropoiesis after in terruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overl oaded rats received 20 daily injections of rHuEpo. During treatment, reticu locytes, soluble transferrin receptor (sTfR), and hematocrit increased prog ressively. This was accompanied by a substantial expansion of spleen erythr opoiesis but a decrease in the bone marrow. Five weeks after treatment, rat s developed a significant degree of aregenerative anemia. Erythropoietic ac tivity, as assessed by reticulocytes, sTfR, erythroid cellularity, iron inc orporation into heme, and the number of erythroid colonies, was severely de pressed 3 weeks after cessation of rHuEpo. This was followed by regeneratio n of erythroblasts and reticulocytes at weeks 6 to 7 post-Epo, but erythroi d progenitors recovered only partially by that time. The anemia was definit ely corrected 2 months after cessation of rHuEpo treatment. Serum Epo level s remained elevated for several weeks, but the sensitivity of marrow erythr oid precursors to Epo was preserved. No rat antibodies to rHuEpo were detec ted, and serum from post-Epo animals did not exert any inhibitory activity on erythropoiesis, In conclusion, after cessation of intensive rHuEpo thera py, there was a strong inhibition of erythropoietic activity with secondary anemia followed by late recovery, This was not due to antibodies or other soluble inhibitory factors, a defect in endogenous Epo production, or a los s of sensitivity to Epo, This may rather represent intrinsic erythroid marr ow exhaustion, mostly at the level of erythroid progenitors but also at lat er stages of erythropoiesis. (C) 2001 by The American Society of Hematology .