Blood, 15 January 2001, Vol. 97, No. 2, pp. 442-448
HEMATOPOIESIS
Cessation of intensive treatment with recombinant human
erythropoietin is followed by secondary anemia
Maude Piron,
Martine Loo,
André Gothot,
Françoise Tassin,
Georges Fillet, and
Yves Beguin
From the Department of Medicine, Division of
Hematology, and the Department of Clinical Biology, Division of
Laboratory Hematology, University of Liège, Liège, Belgium.
Little information is available on the evolution of
erythropoiesis after interruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overloaded rats received 20 daily injections of
rHuEpo. During treatment, reticulocytes, soluble transferrin receptor
(sTfR), and hematocrit increased progressively. This was accompanied by
a substantial expansion of spleen erythropoiesis but a decrease in the
bone marrow. Five weeks after treatment, rats developed a significant
degree of aregenerative anemia. Erythropoietic activity, as assessed by
reticulocytes, sTfR, erythroid cellularity, iron incorporation into
heme, and the number of erythroid colonies, was severely depressed 3 weeks after cessation of rHuEpo. This was followed by regeneration of
erythroblasts and reticulocytes at weeks 6 to 7 post-Epo, but erythroid
progenitors recovered only partially by that time. The anemia was
definitely corrected 2 months after cessation of rHuEpo treatment.
Serum Epo levels remained elevated for several weeks, but the
sensitivity of marrow erythroid precursors to Epo was preserved. No rat
antibodies to rHuEpo were detected, and serum from post-Epo animals did
not exert any inhibitory activity on erythropoiesis. In conclusion, after cessation of intensive rHuEpo therapy, 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 loss of sensitivity to Epo. This may rather represent
intrinsic erythroid marrow exhaustion, mostly at the level of
erythroid progenitors but also at later stages of erythropoiesis.
