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Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1

2000; Elsevier BV; Volume: 6; Issue: 2 Linguagem: Inglês

10.1016/s1083-8791(00)70042-5

1523-6536

Donna Przepiorka, Rima M. Saliba, Karen R. Cleary, Harald E. Fischer, R. Tonai, Herbert A. Fritsche, Issa F. Khouri, Jody Folloder, Naoto T. Ueno, Rakesh Mehra, Cindy Ippoliti, Sergio Giralt, James Gajewski, Michèle L. Donato, David F. Claxton, Ira Braunschweig, Koen van Besien, Paolo Anderlini, Börje S. Andersson, R. Champlin,

Immune Cell Function and Interaction

One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unre l a t e d donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and m i n i m e t h o t rexate for prevention of acute graft-versus-host disease (GVHD).Sixty-eight patient-donor pairs had allelic matches at HLA-DRB1 and HLA-DQB1, 20 pairs had a single mismatch at HLA-DRB1 or HLA-DQB1, and 12 were mismatched at both HLA-DRB1 and HLA-DQB1.Minimum follow-up time was 6 months.Grades 2 to 4 GVHD occurred in 43% of patients with matched donors, 69% with single allele-mismatched donors, and 71% with double allele-mismatched donors; grades 3 to 4 GVHD occurred in 22%, 43%, and 64%, re s p e c t i v e l y.On multivariate analysis, the relative risk of grades 2 to 4 GVHD was 2.2 (95% CI, 1.1-4.5;P = .03)with a single allele mismatch and 2.7 (95% CI, 1.2-6.0;P = .02)with a double allele mismatch.The relative risks of grades 3 to 4 GVHD were 3.0 (95% CI, 1.2-7.6;P = .02)and 5.0 (95% CI, 1.9-12.6;P = .001),re s p e c t i v e l y.Day 100 tre a t m e n t -related mort a l i t y was also adversely affected by allelic mismatching, occurring in 21% of those with matched donors, 50% with single allele-mismatched donors, and 42% with double allele-mismatched donors (P = .02),but overall survival at day 180 did not differ significantly among the 3 groups.Ta c rolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.