Targeted pretransplant host lymphocyte depletion prior to T-cell depleted reduced-intensity allogeneic stem cell transplantation

Michael R. Bishop, Seth M. Steinberg, Ronald E. Gress, Nancy M. Hardy, Donna Marchigiani, Claude Kasten-Sportes, Robert Dean, Steven Z. Pavletic, Juan Gea-Banacloche, Kathleen Castro, Fran Hakim, Michael Krumlauf, Elizabeth J. Read, Charles Carter, Susan F. Leitman, Daniel H. Fowler

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Mixed chimaerism and graft rejection are higher after reduced-intensity allogeneic stem cell transplantation (RIST) with T-cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte-depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4+ counts to <0.05 × 10 9 cells/1. Subjects (n = 18) then received reduced-intensity conditioning followed by ex vivo TCD human leucocyte antigen-matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post-RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3+ cells (P = 00032) after lymphocyte-depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST.

Original languageEnglish (US)
Pages (from-to)837-843
Number of pages7
JournalBritish Journal of Haematology
Volume126
Issue number6
DOIs
StatePublished - Sep 2004

Keywords

  • Allogeneic
  • Graft rejection
  • Reduced-intensity
  • T-cell depletion

ASJC Scopus subject areas

  • Hematology

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