Transplant strategies for patients with myelodysplastic syndromes

Hematopoietic cell transplantation offers potentially curative therapy for patients with myelodysplastic syndrome. The median patient age at diagnosis, however, is about 70 years, which has limited the application of conventional hematopoietic cell transplantation. In addition, the optimum timing of transplantation remains controversial.

The omission of high-dose total body irradiation, dose adjustments of busulfan to achieve defined target levels, the use of fludarabine instead of cyclophosphamide as an immune suppressive agent, the addition of melphalan, and the incorporation of antithymocyte globulin appear to have contributed to better tolerability of new transplant regimens. Reduced-intensity conditioning regimens are associated with a decrease in nonrelapse mortality and allow for successful hematopoietic cell transplantation even in patients 60-70 years of age. Among patients with less advanced/low-risk myelodysplastic syndrome (< 5% marrow myeloblasts), 3-year survivals of 65-75% are achievable with human leucocyte antigen-matched related and unrelated donors. Among patients with more advanced/high-risk disease, the probability of posttransplant relapse ranges from 10 to 40%, and, as a result, relapse-free survival is inferior. In addition to disease stage, comorbid conditions, pretransplant chemotherapy, conditioning regimen and source of stem cells, affect transplant outcome.

Modifications of transplant conditioning regimens have reduced transplant-related mortality, allowing successful hematopoietic cell transplantation in increasingly older patients. Graft versus host disease, both acute and chronic, and posttransplant relapse remain challenging problems.