HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.

Publication Type:

Journal Article

Source:

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Volume 14, Issue 6, p.641-50 (2008)

Keywords:

2008, Adult, Aged, Blood Component Transfusion, Bone Marrow Transplantation, Center-Authored Paper, Clinical Research Division, Cyclophosphamide, Disease-Free Survival, Drug Administration Schedule, Female, Filgrastim, Flow Cytometry Core Facility, Graft Survival, Graft vs Host Disease, Hematologic Neoplasms, Hemoglobinuria, Paroxysmal, Histocompatibility, Humans, Immunosuppressive Agents, Male, Middle Aged, Mycophenolic Acid, Postoperative Care, Postoperative Complications, Research Trials Office Core Facility - Biostatistics Service, Shared Resources, Tacrolimus, Transplantation Conditioning, Transplantation, Homologous, Vidarabine, Whole-Body Irradiation

Abstract:

We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/microL) and platelet recovery (>20,000/microL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.