Effects of hydroxurea, stem cell factor, and erythropoietin in combinationon fetal hemoglobin in the baboon

Objective. Augmentation of the level of fetal hemoglobin (HbF) is considere d therapeutic for patients with sickle cell disease. The objective of this study was to determine the effect of treatment with a combination of erythr opoietin (Epo), stem cell factor (SCF), and hydroxyurea (HU) on HbF levels, Materials and Methods. The effect of treatment with a combination of Epo, S CF, and HU on HbF, F-cell numbers, and globin chain synthesis was evaluated in a baboon model, Results. Treatment with a combination of SCF+Epo resulted in a two-fold inc rease in HbF, F-cells, and F-reticulocytes compared to Epo alone. The combi nation of SCF+Epo+HU resulted in an additional two-fold increase in HbF, wh ereas F-cells and F-reticulocytes increased only 25% compared to the SCF+Ep o regimen. Measurement of differential globin chain synthesis indicated tha t the SCF+Epo+HU treatment also increased the I gamma /V gamma (homologous to human Gy and Ay) synthetic ratio toward the fetal ratio. Conclusions. HU can effectively augment growth factor-induced HbF synthesis in vico. Because I gamma /V gamma ratios are unaffected by erythropoietic stress and similar increases in this ratio have only been observed followin g administration of 5-azacytidine, we suggest that these two agents may sha re a common mechanism of action involving the recruitment of a similar targ et cell population to terminal erythroid differentiation. (C) 2001 Internat ional Society for Experimental Hematology. Published by Elsevier Science In c.