Acute leukemia in adults: novel allogeneic transplant strategies

Abstract

Acute myeloid leukemia (AML) is the most common indication for hematopoietic cell transplantation (HCT). Significant improvements in histocompatibility testing have resulted in identifying better alternative donors to provide grafts; coupled with expanding use of reduced-intensity conditioning (RIC) regimens, patient outcomes have improved. Most AML patients in complete remission now can undergo allogeneic HCT procedures with an anticipated result that approaches that obtained with sibling donors and myeloablative conditioning (MAC). Treatment-related mortality (TRM), relapse, GVHD and, for umbilical cord blood (UCB) grafts, slow engraftment/engraftment failures, however, continue to plague HCT. Newer strategies include the use of double unit UCB HCT and ex vivo expansion of UCB units using: multipotent mesenchymal stromal cells (MSCs); polyamine copper chelator tetraethylenepentamine (TEPA); and Notch ligand. Haploidentical bone marrow and blood HCT are increasing in numbers given the improved outcome with post-HCT cyclophosphamide therapy. Novel chemotherapeutic preparative regimens incorporating agents such as clofarabine and treosulfan, and novel radiation preparative regimens utilizing selective radiation approaches (helical tomotherapy) and targeted myeloablative radioimmunotherapy appear to enhance the anti-AML effect. Immunological approaches with chimeric antigen receptor-redirected T lymphocytes have been added to the armamentarium. Other novel maneuvers include more sophisticated T-cell depletion of the donor graft and post-transplant immunotherapy with regulatory T cell (Treg) therapy and MSCs for GVHD prevention. These and other strategies are improving the outlook of AML HCT recipients.

Keywords:

• Acute leukemia
• Allogeneic hematopoietic cell transplantation
• Treatment-related mortality