The rationale for treatment with recombinant human
erythropoietin (rHuEPO) in
thalassemia came from studies in baboons, thalassemic mice and in erythroid cultures. The results demonstrated an increase in
gamma globin synthesis and consequently in fetal Hb (Hb F) resulting in improvement in erythropoietic parameters. In addition, endogenous serum Epo levels in various forms of
thalassemia were inconsistent and not related to the severity of the
anemia. Therefore, several preliminary studies with rHuEPO were performed, mainly on patients with
beta thalassemia intermedia. The results indicate: a) a significant, dose-related (500 u/kg to 1000 u/kg x 3/week) increase in
thalassemia erythropoiesis without changes in % of Hb F, MCV and MCH, mainly in splenectomized patients; b) the minimum effective dose is 500 u/kg x 3/week; c) there were no major side effects during the continuous treatment period of 9 months. In order to improve both quantitative and qualitative
thalassemia erythropoiesis, several trials were undertaken combining rHuEPO with
hydroxyurea (HU), which is known to increase % Hb F, MCV and MCH without a major effect on Hb levels. The designed trial included 3 to 6 months of HU alone (20 mg/kg x 4/week), or with rHuEPO alone (500 u/kg x 3/week or 375 u/kg x 2/week) or a combination of the two drugs. The results show an additive effect of the two drugs, in some of the patients. It is not known whether the addition of oral
iron to rHuEPO is warranted for maximal erythropoietic response. The major limiting factor in designing large scale clinical trials is the relatively high cost of the
drug. Nevertheless rHuEPO alone or in combination with other Hb F modulating drugs may have a positive effect in
thalassemia with resulting improvement in the quality of life.