title: Evaluation of pretransplant donor anti-recipient cytotoxic and helper T lymphocyte responses as correlates of acute graft-vs.-host disease and survival after unrelated marrow transplantation.
abstract: We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) responses separately in two cohorts of unrelated marrow transplant recipients. Donors and recipients were typed for HLA-A and -B antigens by serologic methods, and for HLA-DRB1 by molecular methods. A single mismatch for a cross-reactive HLA-A or -B antigen or the -DRB1 allele was accepted in patients younger than 36 years if an HLA-A, -B, or -DRB1-matched donor could not be identified. The combination of methotrexate and cyclosporine was used for graft-vs.-host disease (GVHD) prophylaxis, and marrows were not T cell depleted. Donor anti-recipient CTL precursor frequencies showed no correlation with the severity of acute GVHD or with survival after transplantation. HTL responses were detected in the presence of HLA-class II disparity and showed weak correlations with the severity of acute GVHD (p = 0.054) and with survival after transplantation (p = 0.08). These results suggest that testing donor anti-recipient CTL responses before unmodified marrow transplantation does not predict clinically important events and is not likely to help select unrelated donors. With the current availability of molecular genetic methods for assessing HLA-class II compatibility, testing donor anti-recipient HTL responses is not likely to add information that would help select unrelated donors.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pei
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: G
authors.initials: G
authors.lastname: Longton
authors.forename: S
authors.initials: S
authors.lastname: Masewicz
authors.forename: E
authors.initials: E
authors.lastname: Mickelson
authors.forename: E
authors.initials: E
authors.lastname: Petersdorf
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: J
authors.initials: J
authors.lastname: Hansen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005069:Evaluation Studies as Topic; D005260:Female; D006085:Graft Survival / Q000276:immunology* / Q000502:physiology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology / Q000494:pharmacology; D015234:HLA-A Antigens / Q000032:analysis / Q000276:immunology; D015235:HLA-B Antigens / Q000032:analysis / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000276:immunology / Q000494:pharmacology; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D014019:Tissue Donors; D014180:Transplantation; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D015778:Minor Histocompatibility Antigens