Haematopoietic growth factors in the treatment of myelodysplastic syndromes.

Abstract

There are several therapeutic options for myelodysplastic syndrome (MDS) patients but the potentially curative ones are only available for a minority of individuals. At present, in fact, the only two treatments that can prolong survival are allogeneic stem cell transplantation and intensive chemotherapy. The only two haematopoietic growth factors that can be useful in the treatment of selected MDS patients are recombinant human erythropoietin (rHuEpo) and G-CSF. Overall 15 to 20% of patients with MDS respond to rHuEpo treatment but the vast majority of responders are not transfusion-dependent and the doses required to achieve response are > 450 IU/kg per week. Factors predicting response include serum Epo levels <100 mU/ml, female gender and no or low need for transfusion. Recognising potential responders to rHuEpo can be extremely important in individual cases of MDS. G-CSF alone should be used only for short-term treatments. It may be administered to individual patients during an infective episode that does not respond to antibiotic therapy, particularly in the case of fungal infections. In addition, G-CSF may be employed for shortening the length of severe neutropenia following intensive chemotherapy. American and Scandinavian studies have shown that about 40% of MDS patients respond to a combined treatment of rHuEpo with G-CSF with amelioration of anaemia and that response can be maintained for a median duration of 24 months. Using pre-treatment serum Epo levels as a ternary variable (<100, 100-500 or > 500 U/l) and red blood cell transfusion need as a binary variable (<2 or > or =2 units per month), a predictive score for erythroid response to G-CSF plus rHuEpo can be obtained. This score can identify patients with a high probability of erythroid responses (about 75%). Due to the inadequacies of all current treatment modalities, participation in clinical trials should always be encouraged.