Treatment of myelodysplastic syndromes

Therapeutic options have been rapidly evolving for management of patients with the indolent myeloid clonal hemopathies termed myelodysplastic syndromes (MDS). Heterogeneity of MDS has been demonstrated on the basis of marrow morphology and biologic features and has been useful for prognostication into high and low risk groups for transformation to acute leukemia. Such stratification has been important for evaluating responses to various treatments. These therapeutic options include the differentiation-inducing vitamins retinoic acid and vitamin D, and cytokines such as alpha and gamma interferon, to which there has been a generally low response. The use of intensive or low dose chemotherapy has been associated with relatively low response rates, few durable responses and a high degree of hemopoietic toxicity. Allogeneic bone marrow transplantation (BMT) has shown durable responses for a subset of MDS patients, particularly those who are young and who are in the low risk subgroups. however, due to the elderly nature of the majority of MDS patients, and the toxicity associated with BMT, this option has limited utility for most of these patients. Major focus has been on the recent therapeutic use of recombinant human hemopoietic growth factors, particularly G-CSF, GM-CSF and IL3. These agents have been well-tolerated and generally produce a high incidence of sustained improvements in neutrophil counts and marrow morphology, although hemoglobin and platelet counts have generally not been altered. More extensive clinical trials evaluating the impact of these hemopoietic growth factors on the natural history of MDS are ongoing.