Differentiation induction therapy of myelodysplastic syndromes

Myelodysplastic syndromes are a heterogenous group of haemopoietic stem cell disorders characterized by dysplastic haematopoiesis and a defective maturation of a slowly expanding or sometimes of a stable population of haemopoietic progenitors. Defective maturation, which may involve one or more of the marrow cell lineages is regarded as the central pathophysiological feature of myelodysplastic syndromes. Patients with myelodysplastic syndromes respond poorly to conventional cytotoxic chemotherapy, frequently developing a prolonged marrow aplasia. The alternative and more appropriate form of therapy is differentiation induction therapy. The results of few preliminary clinical studies in myelodysplastic patients showed that a combination of differentiating agents is superior to single agent differentiation therapy. An extensive pre-clinical screening of the response of fresh cells from myelodysplastic patients in primary culture is needed to establish the optimal doses and conditions for significant synergies between various differentiating agents followed by large controlled randomized clinical trials based on differentiation induction therapy for patients with myelodysplastic syndromes.