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Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation
Author(s) -
Bishop Michael R.,
Steinberg Seth M.,
Gress Ronald E.,
Hardy Nancy M.,
Marchigiani Donna,
KastenSportes Claude,
Dean Robert,
Pavletic Steven Z.,
GeaBanacloche Juan,
Castro Kathleen,
Hakim Fran,
Krumlauf Michael,
Read Elizabeth J.,
Carter Charles,
Leitman Susan F.,
Fowler Daniel H.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05133.x
Subject(s) - immune system , transplantation , lymphocyte , immunology , stem cell , donor lymphocyte infusion , medicine , biology , graft versus host disease , genetics
Summary 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/l. 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 = 0·0032) 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.