Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.
Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p < 0.05). Patients whose donors were matched at the beta-block had significantly less severe acute graft versus host disease (p < 0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.
Witt
C
C
Department of Clinical Immunology, Royal Perth Hospital, Western Australia.
Sayer
D
D
Trimboli
F
F
Saw
M
M
Herrmann
R
R
Cannell
P
P
Baker
D
D
Christiansen
F
F
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D006085:Graft Survival / Q000276:immunology; D015235:HLA-B Antigens / Q000032:analysis; D015236:HLA-C Antigens / Q000032:analysis; D006683:HLA-DQ Antigens / Q000032:analysis; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000032:analysis; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D016555:Matched-Pair Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D014019:Tissue Donors; D016896:Treatment Outcome
D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains