Table 2.

Locus-specific risks in HLA-mismatched unrelated donor hematopoietic cell transplantation.^6–11

Mismatched Locus	GVHD	GVL Effect	Survival	Approach to Donor Selection
HLA-A	↑		↓	In most series, the presence of either an HLA-A allele or antigen mismatch increases post-transplant risks. In some studies, however, HLA-A antigen mismatches impart higher risks than allele mismatches. Bottom Line: If only HLA-A mismatched donors are available, avoid HLA-A antigen mismatches.
HLA-B	↑		↓	There currently are insufficient data on the relative importance of HLA-B allele and antigen mismatches. Bottom Line: If the donor choices include HLA-B- mismatched donors, assure that there is no linked HLA-C mismatch.
HLA-C	↑	Yes	↓	HLA-C mismatching has consistently been shown to increase mortality after transplantation. In most series, HLA-C antigen mismatches carry higher risks than allele mismatches. In a recent study from Japan, the higher risk of GVHD associated with HLA-C mismatching was accompanied by lower risk for relapse (GVL effect). Risks are also higher when the patient’s mismatched HLA-C allotype is expressed at high levels. Bottom Line: If the donor choices include HLA-C mismatched donors, assure there is no linked HLA-B mismatch. Select HLA-C allele mismatches over HLA-C antigen mismatches. Avoid mismatching for a high- expression HLA-C allotype in the patient.
HLA-DRB1	↑↓		↓	There are insufficient data on the relative risks associated with HLA-DRB1 allele and antigen mismatches. HLA-DRB1 and DQB1 mismatching confer additive risks, as do DRB1/3/4/5 mismatches. Bottom Line: If the donor choices include HLA-DRB1- mismatched donors, assure there is no linked HLA-DRB3 (for DR3, 5, 6); DRB4 (for DR4, 7, 9); DRB5 (for DR2) or HLA- DQB1 mismatch.
HLA-DQB1	↓		↑	Of all the classical HLA genes, only mismatching at HLA- DQB1 does not appear to increase risks, but only if truly a single locus mismatch. HLA-DRB1 and DQB1 mismatching confer additive risks. Bottom Line: If HLA-DQB1-mismatched donors are considered, assure there is no linked HLA-DRB1 mismatch.
HLA-DPB1	↑	Yes	↓	Mismatching at HLA-DPB1 increases GVHD but lowers relapse. Among HLA-DPB1 mismatched transplants, T cell epitope and/or level of HLA-DP expression can define high- risk mismatches which should be avoided. Bottom Line: If matching for HLA 12/12 alleles is not feasible, consider the use of T cell epitope and expression to avoid high-risk HLA-DPB1 mismatches.

^↑increased risk

^↓decreased risk

GVHD, graft-versus-host disease

GVL, graft-versus-leukemia