Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts

Biol Blood Marrow Transplant. 2014 Oct;20(10):1573-9. doi: 10.1016/j.bbmt.2014.05.029. Epub 2014 Jun 5.

Abstract

We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor.

Keywords: Allogeneic transplant; Cord blood; Haploidentical; Unrelated.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cord Blood Stem Cell Transplantation*
  • Female
  • Gene Expression
  • Graft vs Host Disease / prevention & control*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Haplotypes
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use
  • Prospective Studies
  • Recurrence
  • Siblings
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Unrelated Donors

Substances

  • HLA Antigens
  • Immunosuppressive Agents
  • Myeloablative Agonists