HLA-haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Component Transfusion
  • Bone Marrow Transplantation / immunology*
  • Bone Marrow Transplantation / methods
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Filgrastim
  • Graft Survival
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematologic Neoplasms / surgery*
  • Hemoglobinuria, Paroxysmal / surgery*
  • Histocompatibility*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Postoperative Care / methods
  • Postoperative Complications / epidemiology
  • Recombinant Proteins
  • Tacrolimus / administration & dosage
  • Tacrolimus / therapeutic use
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Whole-Body Irradiation

Substances

  • Immunosuppressive Agents
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Vidarabine
  • Mycophenolic Acid
  • fludarabine
  • Filgrastim
  • Tacrolimus