Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation

Best Pract Res Clin Haematol. 2011 Sep;24(3):339-49. doi: 10.1016/j.beha.2011.04.004. Epub 2011 Jul 7.

Abstract

The most advanced frontier of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is represented by the use of an HLA-partially matched relative as donor. In this type of transplantation, donor-derived natural killer (NK) cells, which are alloreactive toward recipient cells, significantly contribute to the eradication of leukemia blasts. Alloreactive NK cells may also kill host dendritic cells and T lymphocytes, thus preventing graft-versus-host disease and graft rejection, respectively. Sophisticated strategies of adoptive infusion of T-cell lines/clones specific for the most life-threatening pathogens (namely cytomegalovirus, Epstein-Barr virus, Aspergillus and Adenovirus) have been envisaged, and successfully tested in a few pilot trials, to protect the recipient in the early post-transplantation period. In these patients, also ex-vivo expanded mesenchymal stromal cells have been shown to be beneficial for preventing graft failure. Novel and effective strategies aimed at further augmenting the graft-versus-leukemia effect and at optimizing prevention/treatment of opportunistic/viral infections are warranted.

Publication types

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

MeSH terms

  • Aspergillosis / immunology
  • Aspergillosis / prevention & control
  • Child
  • Child, Preschool
  • Dendritic Cells / immunology
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Immunotherapy, Adoptive
  • Killer Cells, Natural / immunology
  • Lymphocyte Depletion*
  • Male
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / transplantation
  • Tissue Donors*
  • Transplantation, Homologous
  • Virus Diseases / immunology
  • Virus Diseases / prevention & control