Sustained increase in haemoglobin and RBC following long-term administration of recombinant human erythropoietin to patients with homozygous beta-thalassaemia.

Recombinant human erythropoietin (rHuEPO) was given subcutaneously three times per week in an escalating dose from 500 u/kg to 950 u/kg together with ferrous fumarate 305 mg and folic acid 5 mg/d, to 10 patients from four unrelated Arab families with homozygous beta-thalassaemia. Six splenectomized patients showed a mean (+/- standard error) increase in haemoglobin from 7.1 +/- 0.1 to 9.3 +/- 0.1 g/dl (P = 0.0001), in RBC from 4.0 to 5.0 x 10(12)/l (P = 0.0001) and in nucleated RBC from 32 +/- 7 x 10(10)/l to 82 +/- 6 x 10(10)/l while receiving 750 u/kg three times per week which persisted for 4-11 months. In two patients there was no need for further blood transfusions. In three out of four unsplenectomized patients there were no changes in Hb and RBC despite dose escalation. There were no significant changes in MVC, MCH and reticulocyte count, serum bilirubin, LDH, malonyldialdehyde (MDA) and vitamin E levels. After 13 weeks of rHuEPO there was a mean increase in the percentage of F cells from 31 +/- 10% to 86 +/- 6% (P < 0.003) in three splenectomized patients and in one unsplenectomized patient from 56.4% to 80% without changes in the levels of Hb F. Globin chain synthesis ratios did not change in four responding patients. Mean serum iron and transferrin saturation index did not change, whereas mean serum ferritin increased from 299 +/- 45 micrograms/l to 480 +/- 20 micrograms/l (P < 0.001). In seven responding patients an accelerated linear growth was indicated by positive changes in height standard deviation score for chronological age. Side-effects were minimal throughout the treatment period.