Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders

Biol Blood Marrow Transplant. 2016 May;22(5):895-901. doi: 10.1016/j.bbmt.2016.02.001. Epub 2016 Feb 6.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted.

Keywords: Bone marrow failure syndromes; Cyclophosphamide; HLA-haploidentical; Immunodeficiency; Reduced-intensity conditioning.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage*
  • Female
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Male
  • Mycophenolic Acid / administration & dosage
  • Tacrolimus / administration & dosage
  • Transplantation Conditioning*
  • Unrelated Donors*

Substances

  • Cyclophosphamide
  • Mycophenolic Acid
  • Tacrolimus