Allogeneic transplantation for AML and MDS: GVL versus GVHD and disease recurrence

Abstract

Allogeneic transplantation constitutes curative treatment for acute myeloid leukemia and myelodysplastic syndrome. Its therapeutic effects are to a large extent mediated by GVL effects, but partially offset by treatment-related mortality and loss of quality of life caused by acute and chronic GVHD. Although severe acute and chronic GVHD are associated with a reduction in relapse risk, they are not associated with improved survival. Recent efforts to modulate the GVL-GVH balance include novel methods of in vitro or in vivo T-cell depletion that are associated with a minimal impact on rates of disease recurrence and a dramatically decreased risk for GVHD. Donor selection algorithms may also have a significant impact on transplantation outcomes. Low-expression HLA alleles, particularly HLA-DP, should be incorporated in selection of adult unrelated donors. Evolving data suggest that KIR typing may also be important. High-resolution HLA typing and the importance of fetal-maternal interactions in umbilical cord blood transplantation are also briefly discussed. A combination of donor selection strategies and GVHD prophylaxis methods will favorably affect long-term outcomes and create an environment suitable for effective posttransplantation interventions.