Hematopoietic cell transplantation for myelodysplastic syndrome.

Although high-dose chemotherapy may cure a small subset of patients with myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (HCT) is the only currently available modality that is curative in a large proportion of patients. Approximately 30% to 40% of patients with high-risk MDS and 60% to 80% of patients with low-risk MDS survive long-term in remission. Disease classification and risk assessment schemes, such as the World Health Organization (WHO) Prognostic Scoring System (WPSS), the Revised International Prognostic Scoring System (IPSS-R), and patient characteristics as assessed by the HCT Comorbidity Index (HCT-CI) or other scores, provide guidance for patient management. First, by defining the prognosis of patients without HCT, these tools help physicians decide who should and who should not be transplanted. Second, they predict at least in part how successful a transplant is likely to be. Pretransplant cytogenetics and marrow myeloblast count are the strongest risk factors for post-transplant relapse. The HCT-CI allows physicians to estimate the probability of nonrelapse mortality after HCT; recent data suggest that there is also a relationship to the development of graft-versus-host disease (GVHD). In general, the emphasis has shifted from high-dose therapy, aimed at maximum tumor-cell kill, to reduced-intensity conditioning (RIC), relying on the donor cell-mediated graft-versus-tumor (GVT) effects to eradicate the disease. GVT effects are most prominent in patients who also develop GVHD, especially chronic GVHD. Thus, ongoing work is directed at reducing GVHD while maintaining potent GVT effects and at exploiting the growing knowledge of somatic mutations for the development of targeted therapies.