Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Haematologica. 2016 May;101(5):634-43. doi: 10.3324/haematol.2015.138594. Epub 2016 Feb 11.

Abstract

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II-IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588.

Trial registration: ClinicalTrials.gov NCT00943800 NCT01810588.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Comorbidity
  • Cord Blood Stem Cell Transplantation* / adverse effects
  • Disease Progression
  • Female
  • Graft Survival
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • HLA Antigens* / genetics
  • HLA Antigens* / immunology
  • Haplotypes*
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cells* / immunology
  • Hematopoietic Stem Cells* / metabolism
  • Histocompatibility Testing
  • Humans
  • Kaplan-Meier Estimate
  • Leukocyte Count
  • Male
  • Middle Aged
  • Mortality
  • Neutrophils
  • Recurrence
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors*
  • Young Adult

Substances

  • HLA Antigens

Associated data

  • ClinicalTrials.gov/NCT00943800
  • ClinicalTrials.gov/NCT01810588