T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients

Br J Haematol. 2012 Apr;157(2):205-19. doi: 10.1111/j.1365-2141.2012.09048.x. Epub 2012 Feb 8.

Abstract

CD34-selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft-versus-host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post-transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34-selected 8-10/10 human leucocyte antigen (HLA)-matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n = 13) or non-malignant (n = 6) diseases. T cells were added back to achieve total dose 1·0-2·5 × 10(5) CD3(+) /kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade II-IV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15·8%, 23·3%, and 0%, respectively. One patient developed PTLD. One-year infection-related mortality was 5·6%. T cell immune reconstitution was delayed. One-year overall survival was 82·3%. Five patients with malignant disease ultimately died from progressive disease. CD34-selected MUD PBSCT using a defined dose of T cell add-back resulted in high rates of engraftment and low risk of grade II-IV aGVHD, early transplantation-related mortality, and extensive cGVHD.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD34*
  • Child
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Histocompatibility Testing
  • Humans
  • Lymphocyte Depletion*
  • Lymphocyte Transfusion*
  • Male
  • Neoplasms / mortality
  • Neoplasms / therapy
  • Peripheral Blood Stem Cell Transplantation*
  • Prospective Studies
  • Survival Rate
  • Unrelated Donors*

Substances

  • Antigens, CD34