Complete donor T cell chimerism predicts lower relapse incidence after standard double umbilical cord blood reduced-intensity conditioning regimen allogeneic transplantation in adults

Biol Blood Marrow Transplant. 2015 Jan;21(1):180-4. doi: 10.1016/j.bbmt.2014.08.018. Epub 2014 Aug 28.

Abstract

Double umbilical cord blood (dUCB) allogeneic transplantation after a low-dose total body irradiation, cyclophosphamide, and fludarabine (TCF)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there are little data regarding the long-term outcome of CD3(+) T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases who received dUCB allogeneic transplants conditioned with TCF were included in this retrospective study. Peripheral blood CD3(+) TCC was considered until day +100 after transplantation to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3(+) TCC, respectively, within the first 100 days after transplantation. With a median follow-up of 36 months, 3 year-overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) were 61%, (95% confidence interval [CI], 43% to 75%); 50% (95% CI, 32.5% to 66%), and 28% (95% CI, 16% to 44%), respectively. In univariate analysis, a full CD3(+) TCC was associated with a better 3-year DFS: 59% (95% CI, 39% to 75.5%) versus 14% (95% CI, 7% to 46%); hazard ratio (HR), .24 (.09 to .65); P = .005 and a lower CIR: 24% (95% CI, 21.5% to 57%) versus 78% (95% CI, 52% to 99%); HR, .18 (.05 to .50); P = .004. In multivariate analysis, a full CD3(+) TCC remained associated with a lower CIR (HR, .17 [.028 to .99]; P = .049). CD3(+) TCC has no impact on graft-versus-host disease and nonrelapse mortality in this study. In conclusion, here, full CD3(+) TCC was independently associated with a lower risk of relapse in adults receiving a dUCB TCF RIC allogeneic transplantation. This highlights the need to develop immunotherapy approaches allowing for early conversion to full chimerism after this type of transplantation.

Keywords: Adults; Chimerism; Double cord blood allogeneic stem cells transplantation; Outcomes; RIC; Relapse; TCF conditioning.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cord Blood Stem Cell Transplantation / methods*
  • Cyclophosphamide / therapeutic use
  • Female
  • Graft Survival
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use*
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Survival Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation
  • Transplantation Chimera / immunology*
  • Transplantation Conditioning / methods*
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Whole-Body Irradiation

Substances

  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Cyclophosphamide
  • Vidarabine
  • fludarabine