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

Leo Luznik, Paul V. O'Donnell, Heather J. Symons, Allen R. Chen, M. Susan Leffell, Marianna Zahurak, Ted A. Gooley, Steve Piantadosi, Michele Kaup, Richard F. Ambinder, Carol Ann Huff, William Matsui, Javier Bolaños-Meade, Ivan Borrello, Jonathan D. Powell, Elizabeth Harrington, Sandy Warnock, Mary Flowers, Robert A. Brodsky, Brenda M. SandmaierRainer F. Storb, Richard J. Jones, Ephraim J. Fuchs

Research output: Contribution to journalArticlepeer-review

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/μL) and platelet recovery (>20,000/μL) 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.

Original languageEnglish (US)
Pages (from-to)641-650
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Bone marrow transplantation
  • Conditioning regimens
  • Cyclophosphamide
  • Histocompatibility antigens
  • Leukemia
  • Lymphoma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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