Myelodysplasia: the good, the fair and the ugly

The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders. The molecular pathogenesis of the disease is poorly understood and a large number of fundamental biologic questions remain. This heterogeneity presents challenges in selecting therapy for individual patients as well as for evaluating response to treatment. Only a small number of randomized clinical trials have been conducted, although three new drugs (azacitidine, lenalidomide, and decitabine) have been approved for use in the last few years. Response to most therapies occurs slowly, and sometimes months elapse before response can be evaluated. The response rates for most drugs used or studied for MDS range from <10%-20%. Some therapies seem more promising than others: immunosuppression with antithymocyte globulin results in extended durations of benefit in responders; lenalidomide induces a very high erythroid response rate in patients with del 5q- karyotype. The DNA hypomethylating agents, azacitidine and decitabine, can be of significant benefit for a fraction of patients and further investigation is needed to determine whether higher response rates occur in particular subgroups of MDS patients. Further refinements of dose and schedule of administration are also under investigation.