Low-dose total body irradiation and fludarabine conditioning for HLA class I-mismatched donor stem cell transplantation and immunologic recovery in patients with hematologic malignancies: a multicenter trial.

Abstract

HLA-mismatched grafts are a viable alternative source for patients without HLA-matched donors receiving ablative hematopoietic cell transplantation (HCT), although their use in reduced intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT has been not well established. Here, we extended HCT to recipients of HLA class I-mismatched grafts to investigate whether NMA conditioning can establish stable donor engraftment. Fifty-nine patients were conditioned with fludarabine (Flu) 90 mg/m(2) and 2 Gy total body irradiation (TBI), followed by immunosuppression with cyclosporine (CsA) 5.0 mg/kg twice a day and mycophenolate mofetil (MMF) 15 mg/kg 3 times a day for transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from related (n = 5) or unrelated donors (n = 54) with 1 antigen +/- 1 allele HLA class I mismatch or 2 HLA class I allele mismatches. Sustained donor engraftment was observed in 95% of the evaluable patients. The incidence of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) was 69% and 41%, respectively. The cumulative probability of nonrelapse mortality (NRM) was 47% at 2 years. Two-year overall and progression-free survival (OS, PFS) was 29% and 28%, respectively. NMA conditioning with Flu and low-dose TBI, followed by HCT using HLA class I-mismatched donors leads to successful engraftment and long-term survival; however, the high incidence of aGVHD and NRM needs to be addressed by alternate GVHD prophylaxis regimens.

• Authors: Hirohisa Nakamae, Barry E Storer, Rainer Storb, Jan Storek, Thomas R Chauncey, Michael A Pulsipher, Finn B Petersen, James C Wade, Michael B Maris, Benedetto Bruno, Jens Panse, Effie Petersdorf, Ann Woolfrey, David G Maloney, Brenda M Sandmaier
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 16 Issue 3 Pg. 384-94 (Mar 2010) ISSN: 1523-6536 [Electronic] United States
• PMID: 19900571 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Histocompatibility Antigens Class I
• Myeloablative Agonists
• Vidarabine
• fludarabine

Topics

• Adolescent
• Adult
• Aged
• Blood Cell Count
• Cell Count
• Communicable Diseases (etiology)
• Dendritic Cells (cytology)
• Disease-Free Survival
• Female
• Graft Rejection
• Graft vs Host Disease (diagnosis)
• Hematologic Neoplasms (therapy)
• Histocompatibility (immunology)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Kaplan-Meier Estimate
• Lymphocytes (cytology)
• Male
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Peripheral Blood Stem Cell Transplantation (adverse effects, methods)
• Postoperative Complications
• Recurrence
• T-Lymphocytes (cytology)
• Tissue Donors
• Transplantation Chimera
• Transplantation Conditioning (methods)
• Treatment Outcome
• Vidarabine (analogs & derivatives, therapeutic use)
• Whole-Body Irradiation (methods)
• Young Adult