THE EFFECT OF RECOMBINANT-HUMAN-ERYTHROPOIETIN ON CIRCULATING HEMATOPOIETIC PROGENITOR CELLS IN ANEMIC PREMATURE-INFANTS

In vitro and animal studies suggest that high concentrations of recomb inant human erythropoietin (rHuEPO) might divert multipotent progenito rs into erythroid maturation at the expense of granulocyte production. We determined whether changes of number and lineage commitment of per ipheral blood progenitor cells occur in premature infants during thera py with rHuEPO. Thirty preterm infants were randomly assigned either t o receive 300 IU of eopoetin alpha s.c. per kilogram body weight three times a week for four weeks or to a control group. At study entry and after two weeks of treatment the numbers of circulating BFU-E, granul ocyte-macrophage colony-forming units (CFU-GM) and granulocyte-erythro cyte-macrophage-megakaryocyte CFU (CFU-GEMM) were analyzed by semisoli d culture technique, CD34(+) cells and early myeloid CD34(+)CD45RA(-) progenitors by flow cytometry. As compared with the control group, rHu EPO treatment did not exert any significant modulatory effect on numbe rs of CFU-GM, nor was there a significant change in numbers of BFU-E, CFU-GEMM, total-CFU, percentage of CD34(+) or CD34(+)CD45RA(-) cells. Mean neutrophil count was not significantly reduced at any period duri ng the study. Compared with the control group, the infants receiving r HuEPO had higher hematocrit values (p = 0.003) and absolute reticulocy te counts (p < 0.001). The median cumulative volume of blood transfuse d per kilogram per day was 0.86 ml (first quartile 0.5 ml; third quart ile 1.1 ml) in the control group and 0 ml (first quartile 0 ml; third quartile 0.47 ml) in the rHuEPO group (p = 0.038). We conclude using a relatively high dose of rHuEPO in premature infants, no significant i n vivo effect on circulating peripheral blood progenitor or neutrophil count could be detected.