"No donor"? Consider a haploidentical transplant

Blood Rev. 2015 Mar;29(2):63-70. doi: 10.1016/j.blre.2014.09.009. Epub 2014 Sep 30.

Abstract

Haploidentical stem cell transplantation (HaploSCT) is an attractive option for patients requiring a hematopoietic stem cell transplant who do not have an HLA-matched donor, because it is cheaper, can be performed faster, and may extend transplantation to virtually all patients in need. Significant advances have been made in the recent decade with dramatic improvement in treatment outcomes. Historically, overcoming the HLA-incompatibility barrier has been a significant limitation to the expansion of this form of transplant. While ex vivo T-cell depletion effectively prevented the development of acute GVHD, it was associated with a higher treatment-related mortality, in excess of 40% in some series, due to a significant delay in recovery of the adaptive immune system. Newer methods have successfully maintained the memory T cells in the graft and/or selectively depleted alloreactive T cells, and are associated with improved treatment outcomes. Post-transplant cyclophosphamide for GVHD prevention has proven very effective in controlling GVHD with lower incidence of infectious complications and treatment-related mortality-as low as 7% at 1 year-and has become the new standard in how this transplant is performed. Here, we reviewed the current experience with this approach and various other strategies employed to control alloreactivity in this setting, including selective depletion of T cells from the graft, as well as we discuss post-transplantation therapy to prevent disease relapse and improve immunologic reconstitution.

Keywords: Alpha-beta T cell depletion; Cellular therapy; Graft engineering; Haploidentical transplantation; Post-transplantation cyclophosphamide.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Engineering / methods
  • Cell- and Tissue-Based Therapy / methods
  • Cyclophosphamide / therapeutic use
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Graft vs Host Disease / therapy*
  • Haploidy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide