title: The impact of T-cell depletion on the effects of HLA DR beta 1 and DQ beta allele matching in HLA serologically identical unrelated donor bone marrow transplantation.
abstract: Unrelated donor bone marrow transplants have been associated with relatively high rates of acute graft-vs.-host disease and treatment-related mortality. These complications reflect histo-incompatibility between donor and recipient. Molecular technology has recently been applied to HLA typing to identify alleles not distinguishable with serologic typing techniques. We report results in 92 unrelated marrow transplant recipients who were HLA seroidentical with donor HLA-A, -B, and -DR antigens and assess the effect of DR beta 1 and DQ beta compatibility using sequence specific oligonucleotide primers. Forty-eight patients received T-cell depleted marrow grafts, and 44 received unmodified grafts. Among recipients of unmodified marrow grafts, matching for both DR beta 1 and DQ beta reduced the rate of grade 3-4 acute graft-vs.-host disease to 38 +/- 20% vs. 73 +/- 20% among recipients mismatched for either allele (p = 0.02). This difference was not observed in recipients of T-cell depleted marrow grafts. Multivariate analysis confirmed matching for both DR beta 1 and DQ beta loci (p = 0.015), and receiving a T-cell depleted graft (p = 0.008) independently predicted for reduced risk of grade 3-4 acute graft-vs.-host disease. In conclusion, both DR beta 1 and DQ beta appear biologically important for development of acute graft-vs.-host disease in patients receiving unmanipulated marrow grafts for unrelated donor transplant.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Department of Hematology, Houston 77030, USA. jgajewski@utmdacc.mda.uth.onc.edu
authors.forename: J
authors.initials: J
authors.lastname: Gajewski
authors.forename: D
authors.initials: D
authors.lastname: Gjertson
authors.forename: M
authors.initials: M
authors.lastname: Cecka
authors.forename: R
authors.initials: R
authors.lastname: Tonai
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
authors.forename: L
authors.initials: L
authors.lastname: Hunt
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: K W
authors.initials: KW
authors.lastname: Chan
authors.forename: S
authors.initials: S
authors.lastname: Feig
authors.forename: M
authors.initials: M
authors.lastname: Territo
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: H
authors.initials: H
authors.lastname: Fischer
authors.forename: L
authors.initials: L
authors.lastname: Babbitt
authors.forename: C
authors.initials: C
authors.lastname: Ippolitti
authors.forename: G
authors.initials: G
authors.lastname: Schiller
authors.forename: M
authors.initials: M
authors.lastname: Lill
authors.forename: D
authors.initials: D
authors.lastname: Warkentin
authors.forename: J
authors.initials: J
authors.lastname: Neumann
authors.forename: L
authors.initials: L
authors.lastname: Petz
authors.forename: P
authors.initials: P
authors.lastname: Terasaki
authors.forename: R
authors.initials: R
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D012044:Regression Analysis; D012699:Serology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens