On the use of hydroxyurea/erythropoietin combination therapy for sickle cell disease.

Seven sickle cell disease (SCD) patients [sickle cell anaemia = 4 (males 2, females 2, age range 18-40 years), and sickle cell beta (0)-thalassaemia = 3 (all females, age range 20-47 years)], suffering from a severe form of the disease were enrolled in a treatment protocol using hydroxyurea (HU) for up to 12 months followed by a combination therapy with HU and human recombinant erythropoietin (rHuEpo; using 400 U/kg/week i.v.) for 3-4 weeks. Following the withdrawal of rHuEpo the patients were maintained on HU alone. The patients were characterised on the basis of the 'severity index' prior to the initiation of the therapy. Haematological and relevant biochemical parameters, Hb A2 fetal haemoglobin (HbF), HbF cells, reticulocytes and platelet counts were estimated at least at three occasions to determine the mean and range of the parameters. During the treatment period the patients were followed every 2-4 weeks where the haematological and biochemical parameters were assessed. The results were separately analysed and mean +/- SD were obtained for each parameter at the end of each protocol. The statistical significance of the difference in the results obtained on treatment and the baseline results was examined using the paired t test. No toxic side effects of HU and rHuEpo (as judged from reduction in platelet and white blood cell count) were documented during and after the whole period of treatment. The patients showed a significant clinical improvement. Total haemoglobin, haematocrit, red cell count, HbF and HbF cells increased, while white blood cells, reticulocyte counts and bilirubin level decreased. Platelet count decreased but remained within the normal range. The results revealed that 5 of the patients on HU treatment showed a significant increase in the HbF level and HbF cells, while 2 patients (1 sickle cell anaemia and 1 Hb S/beta(0)-thalassaemia patient) did not and were considered as 'non-responders'. The rHuEpo and HU combination therapy elevated the HbF level, with a varying degree, in all patients except 2, who had already reached a high HbF level and showed a decrease in HbF during the rHuEpo protocol. Variable individual response to both HU and rHuEpo therapy was a common feature. We recommend the use of HU for the treatment of SCD and a combination therapy using HU and rHuEpo for the non-responders.