FETAL HEMOGLOBIN AND F-CELL RESPONSES TO LONG-TERM HYDROXYUREA TREATMENT IN YOUNG SICKLE-CELL PATIENTS

We have studied the cellular and molecular responses to long-term hydr oxyurea (HU) treatment in 29 severely affected young patients with sic kle cell disease (mean age, 10.9 +/- 4.1 years). Patients received HU at 20 mg/kg/d on 4 consecutive days per week initially, with a monthly escalated dose avoiding marrow-toxicity (mean steady-state dose, 34.2 +/- 4.6 mg/kg/d) for 12 to 36 months (mean duration, 22 months). The studied parameters were hemoglobin F (HbF), F reticulocytes (F retics) , F cells, the amount of HbF per F cell (F/F cell), polymer tendency a t 40% and 70% oxygen saturation, and hemolysis. Initial HbF (Fi) was d ispersed (from 0.85% to 13.9%). HbF increased in all patients but 1. H bF at maximal response (Fmax) reached a sustained level varying from a 1.5-fold to a 16-fold Pi after a variable delay (6 to 24 months). Fma x was not related to HU dosage, but Delta F (Fmax-Fi) was strongly cor related to Delta MCV (MCVmax-MCVi). HbF increase resulted from the inc rease of both F cells and F/F cell. In this rather short series, Fi an d Fmax were not significantly associated with age, gender, or P-globin haplotype. Neither Fmax nor Delta F was related to bone marrow reserv e, as measured by baseline reticulocyte or neutrophil counts. However, Fmax was highly dependent on Pi. When patients are individualized int o three groups according to Fmax (group 1, Fmax >20% [12 patients]; gr oup 2, 10% < Fmax < 20% [11 patients]; group 3, Fmax <10% [5 patients] ), Pi is significantly different between groups, being the highest in group 1. In addition, the best responders (group 1) were significantly different from patients in the two other groups with higher levels of total hemoglobin, decreased bilirubin, and decreased polymer tendency . (C) 1998 by The American Society of Hematology.