• Lower GVHD after haploidentical transplant with posttransplant cyclophosphamide compared with HLA-matched unrelated donor transplant.• Comparable overall survival after haploidentical compared with matched unrelated donor transplant for AML.We studied adults with acute myeloid leukemia (AML) after haploidentical (n 5 192) and 8/8 HLA-matched unrelated donor (n 5 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P 5 .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P 5 .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P 5 .05) and 34% vs 52% (P 5 .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P 5 .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P 5 .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. (Blood. 2015;126(8):1033-1040

Allogeneic marrow transplantation can cure sickle cell disease; however, HLAmatched donors are difficult to find, and the toxicities of myeloablative conditioning are prohibitive for most adults with this disease. We developed a nonmyeloablative bone marrow transplantation platform using related, including HLAhaploidentical, donors for patients with sickle cell disease. The regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation, and graft-versus-host disease

Summary Chronic graft-versus-host disease (GVHD) is the leading cause of late, non-relapse, mortality and disability in allogeneic hematopoietic cell transplantation (HCT) patients and a major obstacle to improving outcomes. Chronic GVHD biology remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: Summarize the current “state-of-the-science” regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps.Develop working hypotheses/overriding concepts for chronic GVHD development.Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies.Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations. This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD.