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

Donna Przepiorka, Rima Saliba, Karen Cleary, Harald Fischer, Richard Tonai, Herbert Fritsche, Issa F. Khouri, Jody Folloder, Naoto T. Ueno, Rakesh Mehra, Cindy Ippoliti, Sergio Giralt, James Gajewski, Michele Donato, David Claxton, Ira Braunschweig, Koen Van Besien, Paolo Anderlini, Borje S. Andersson, Richard Champlin

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate 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%, respectively. 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), respectively. Day 100 treatment-related mortality 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. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.

Original languageEnglish (US)
Pages (from-to)190-197
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume6
Issue number2 A
StatePublished - 2000
Externally publishedYes

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HLA-DRB1 Chains
Unrelated Donors
Tacrolimus
Graft vs Host Disease
Transplantation
Bone Marrow
Alleles
Tissue Donors
HLA-A Antigens
HLA-B Antigens
HLA-DR Antigens
HLA Antigens
HLA-DQB1 antigen
Multivariate Analysis
Transplants
Survival
Mortality

Keywords

  • HLA-DQB1
  • HLA-DRB1
  • Tacrolimus
  • Unrelated-donor marrow transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

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. / Przepiorka, Donna; Saliba, Rima; Cleary, Karen; Fischer, Harald; Tonai, Richard; Fritsche, Herbert; Khouri, Issa F.; Folloder, Jody; Ueno, Naoto T.; Mehra, Rakesh; Ippoliti, Cindy; Giralt, Sergio; Gajewski, James; Donato, Michele; Claxton, David; Braunschweig, Ira; Van Besien, Koen; Anderlini, Paolo; Andersson, Borje S.; Champlin, Richard.

In: Biology of Blood and Marrow Transplantation, Vol. 6, No. 2 A, 2000, p. 190-197.

Research output: Contribution to journalArticle

Przepiorka, D, Saliba, R, Cleary, K, Fischer, H, Tonai, R, Fritsche, H, Khouri, IF, Folloder, J, Ueno, NT, Mehra, R, Ippoliti, C, Giralt, S, Gajewski, J, Donato, M, Claxton, D, Braunschweig, I, Van Besien, K, Anderlini, P, Andersson, BS & Champlin, R 2000, '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', Biology of Blood and Marrow Transplantation, vol. 6, no. 2 A, pp. 190-197.
Przepiorka, Donna ; Saliba, Rima ; Cleary, Karen ; Fischer, Harald ; Tonai, Richard ; Fritsche, Herbert ; Khouri, Issa F. ; Folloder, Jody ; Ueno, Naoto T. ; Mehra, Rakesh ; Ippoliti, Cindy ; Giralt, Sergio ; Gajewski, James ; Donato, Michele ; Claxton, David ; Braunschweig, Ira ; Van Besien, Koen ; Anderlini, Paolo ; Andersson, Borje S. ; Champlin, Richard. / 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. In: Biology of Blood and Marrow Transplantation. 2000 ; Vol. 6, No. 2 A. pp. 190-197.
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abstract = "One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate 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{\%}, respectively. 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), respectively. Day 100 treatment-related mortality 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. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.",
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AU - Przepiorka, Donna

AU - Saliba, Rima

AU - Cleary, Karen

AU - Fischer, Harald

AU - Tonai, Richard

AU - Fritsche, Herbert

AU - Khouri, Issa F.

AU - Folloder, Jody

AU - Ueno, Naoto T.

AU - Mehra, Rakesh

AU - Ippoliti, Cindy

AU - Giralt, Sergio

AU - Gajewski, James

AU - Donato, Michele

AU - Claxton, David

AU - Braunschweig, Ira

AU - Van Besien, Koen

AU - Anderlini, Paolo

AU - Andersson, Borje S.

AU - Champlin, Richard

PY - 2000

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N2 - One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate 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%, respectively. 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), respectively. Day 100 treatment-related mortality 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. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.

AB - One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate 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%, respectively. 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), respectively. Day 100 treatment-related mortality 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. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.

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