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An advantage of CD34+ cell selection over antibody purging is that a component allograft is produced comprising a stem cell enriched and an unadsorbed fraction, the latter containing T cells which may be used for post-transplant immunotherapy. Initial reports with PBSC allografts suggested that T cell depletion (TCD) by CD34+ cell selection and post-graft cyclosporin A +/- methotrexate was insufficient prophylaxis against acute GVHD. We compared sequential TCD (of a CD34+ cell-selected fraction) using a second (CD2) immunoaffinity step or Campath-1M monoclonal antibody and complement. Since a high stem cell 'dose' enhances engraftment across HLA barriers and improves overall post-transplant outcome, the recovery of CD34+ cells and progenitors were assessed. Sequential positive (CD34+) and negative (CD2+) immunoaffinity selection resulted in a 3.4 log depletion of T cells as compared to a 4.05 log depletion when CD34+ cell selection was followed by Campath-1M treatment. Recoveries of CD34+ cells, CFU-GM and BFU-E following double depletion using CD34+ cell selection plus CD2+ cell depletion were 28, 25 and 17% as compared to 20, 18 and 16% when CD34+ cells were treated with Campath-1M. The unadsorbed fraction contained 85% of the original T cells, from which donor leukocyte infusions in the range of 10(5) to 10(7) CD3+ cells per kg body weight of the recipient were harvested. Despite the advantages of component allografts, the loss of stem/progenitor cells may restrict sequential TCD steps unless single BM harvests are supplemented and/or replaced with mobilised PBSCs.

Original publication

DOI

10.1038/sj.bmt.1701296

Type

Journal article

Journal

Bone Marrow Transplant

Publication Date

07/1998

Volume

22

Pages

117 - 124

Keywords

Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm, Antigens, CD34, Bone Marrow Purging, Bone Marrow Transplantation, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cell Transplantation, Humans, Immunosorbent Techniques, Lymphocyte Depletion, T-Lymphocytes, Transplantation, Autologous, Transplantation, Homologous