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.
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.
Przepiorka
D
D
Baylor College of Medicine Center for Cell and Gene Therapy, Houston, Texas 77030, USA. donnap@bcm.tmc.edu
Saliba
R
R
Cleary
K
K
Fischer
H
H
Tonai
R
R
Fritsche
H
H
Khouri
I F
IF
Folloder
J
J
Ueno
N T
NT
Mehra
R
R
Ippoliti
C
C
Giralt
S
S
Gajewski
J
J
Donato
M
M
Claxton
D
D
Braunschweig
I
I
van Besien
K
K
Anderlini
P
P
Andersson
B S
BS
Champlin
R
R
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000401:mortality; D005260:Female; D000069585:Filgrastim; D005802:Genes, MHC Class II; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006683:HLA-DQ Antigens / Q000097:blood* / Q000235:genetics; D006684:HLA-DR Antigens / Q000097:blood* / Q000235:genetics; D019337:Hematologic Neoplasms / Q000628:therapy; D006648:Histocompatibility / Q000187:drug effects*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011994:Recombinant Proteins; D012307:Risk Factors; D015996:Survival Rate; D016559:Tacrolimus / Q000494:pharmacology*; D014019:Tissue Donors; D016896:Treatment Outcome
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim; D016559:Tacrolimus; D008727:Methotrexate