HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia

Biol Blood Marrow Transplant. 2014 Apr;20(4):571-6. doi: 10.1016/j.bbmt.2014.01.015. Epub 2014 Jan 22.

Abstract

We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given T cell-depleted, CD34(+) positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of T cell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.

Keywords: Fanconi anemia; Haploidentical stem cell transplantation; Reduced-intensity conditioning; T cell depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD34 / immunology
  • Child
  • Fanconi Anemia / immunology
  • Fanconi Anemia / mortality
  • Fanconi Anemia / pathology
  • Fanconi Anemia / therapy*
  • Female
  • Graft Survival*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • HLA Antigens / immunology
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Lymphocyte Depletion
  • Male
  • Myeloablative Agonists / therapeutic use*
  • Prospective Studies
  • Survival Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use

Substances

  • Antigens, CD34
  • HLA Antigens
  • Myeloablative Agonists
  • Vidarabine
  • fludarabine