The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial. HLA Haplotypes and Haploidentical Transplants The short arm of chromosome 6 is home to the human major histocompatibility complex (MHC) genes, which code for human leukocyte antigens (HLA): during meiosis, the MHC region does not undergo "crossing over" (except for rare events), and we inherit one HLA haplotype from the father and one from the mother. Biology of HAPLO Transplants The double problem of a HAPLO transplant is rejection of the graft, or host versus graft (HvG), and rejection of the host, or graft versus host disease (GvHD), and this double problem was the cause of failure of initial attempts. The first successful haplotype mismatch transplants were carried out in the early 1980s in severe combined immunodeficiency (SCID) patients, in whom the risk of rejection is minimal [2]: GvHD was prevented using T cell depletion (TCD) in the absence of any additional posttransplant GvHD prophylaxis Unmanipulated Marrow Grafts following a Nonmyeloablative Conditioning Regimen (NMA) and PT-CY The John Hopkins group hypothesized 40 years ago that high dose cyclophosphamide (CY), given 3 days after infusion of mismatched grafts, would protect rats from graft versus host disease (GvHD) Unmanipulated Marrow Grafts following a Myeloablative (MA) Conditioning Regimen A study using PT-CY and myeloablative conditioning (MAC) regimens has shown a low incidence of graft failure (<5%), a low incidence of acute grades II-IV GvHD (18%), a very low rate of severe grades III-IV acute GvHD (3%), and relapse as expected with a conventional CyA+MTX GvHD prophylaxis [10]. Unmanipulated Peripheral Blood Grafts and PT-CY Several centers have elected to use exclusively peripheral blood (PB) as a stem cell source in place of bone marrow (BM), based on donor preference, inability to secure operating room hours, and outcome considerations. These centers are unwilling to use BM and have thus adopted the Baltimore protocol using unmanipulated PB instead of BM. Results have been unexpectedly encouraging: this is clear when PB is given after the original Baltimore NMA conditioning regimen. In a recent paper, unmanipulated BM and PB have been compared in the NMA setting: incidence of acute and chronic GvHD, nonrelapse mortality, relapse, and survival were quite comparabl
