Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders

• Published in: Blood 2012-10, Vol.120 (14), p.2918-2924
• Main Authors: Horan, John, Wang, Tao, Haagenson, Michael, Spellman, Stephen R., Dehn, Jason, Eapen, Mary, Frangoul, Haydar, Gupta, Vikas, Hale, Gregory A., Hurley, Carolyn K., Marino, Susana, Oudshoorn, Machteld, Reddy, Vijay, Shaw, Peter, Lee, Stephanie J., Woolfrey, Ann
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood Donors; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials and Observations; Female; Graft Rejection - immunology; Graft vs Host Disease - etiology; Graft vs Host Disease - mortality; Hematologic and hematopoietic diseases; Hematologic Diseases - complications; Hematologic Diseases - therapy; Histocompatibility - immunology; HLA Antigens - immunology; Humans; Infant; Infant, Newborn; Medical sciences; Middle Aged; Peripheral Blood Stem Cell Transplantation; Survival Rate; Transplantation; Unrelated Donors; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-03-417758

The importance of human leukocyte antigen (HLA) matching in unrelated donor transplantation for nonmalignant diseases (NMD) has yet to be defined. We analyzed data from 663 unrelated marrow and peripheral blood stem cell transplants performed from 1995 to 2007 for treatment of NMD. Transplantation from a donor mismatched at the HLA-A, -B, -C, or -DRB1, but not -DQB1 or -DPB1, loci was associated with higher mortality in multivariate analyses (P = .002). The hazard ratio for mortality for single (7/8) and double mismatched (6/8) transplants was 1.29 (0.97-1.72; P = .079) and 1.82 (1.30-2.55; P = .0004), respectively, compared with 8/8 matched transplants. HLA mismatches were not associated with acute or chronic GVHD, but were strongly associated with graft failure. After adjustment for other factors, the odds ratio for graft failure for 7/8 and 6/8 (allele and/or antigen) matched pairs compared with 8/8 matched transplants was 2.81 (1.74-4.54; P < .0001) and 2.22 (1.26-3.97; P = .006), respectively. Patients with NMD should receive transplants from allele matched (8/8) donors if possible. Unlike the case with malignancies, HLA mismatching in NMD is associated with graft failure rather than GVHD.