Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: Matching for transplants from related haploidentical donors

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Abstract
The utility of the MLC assay as a test of HLA‐D region matching and predictor of acute graft‐versus‐host disease (GvHD) was evaluated in 157 patients receiving marrow grafts from HLA‐A, B identical related haploidentical donors. All donors and recipients were tested by HLA‐DR serology, by Dw phenotyping with homozygous typing cells (HTC) and by standard MLC. Ninety‐nine of the donor‐recipient pairs were mismatched for a serologically defined HLA‐DR antigen while 109 pairs were mismatched for the HLA‐D region by HTC typing. Donor anti‐recipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from ‐4% to 100%, with a median of 25%. A comparison of reactivity in MLC with presence or absence of matching by Dw phenotyping, however, showed a significant overlap in the distribution of RRs from HLA‐Dw matched versus Dw mismatched pairs, suggesting that the MLC was not a reliable predictor of HLA‐Dw matching. Using an optimally‐defined cutoff of 3% RR, the MLC was correlated with risk of developing clinically significant grades II–IV acute GvHD (p = 0.03) but not with risk of developing severe grades III‐IV GvHD (p = 0.18). In contrast, matching by Dw phenotype was a significant predictor of GvHD, with Dw‐compatible transplant recipients less likely to develop either grades II‐IV (p = 0.004) or III‐IV (p = 0.036) GvHD than Dw‐incompatible transplant recipients. Overall, these results underscore the difficulty in using the MLC to measure HLA‐D region compatibility and predict the risk of severe graft‐versus‐host disease among patients receiving related haploidentical marrow grafts. HLA‐D (HTC) typing results correlate primarily with DRB compatibility, and with the advent of DRB1 allele matching by sequence‐specific oligonucleotide probes (SSOP) or by direct sequencing, the precision in donor matching achievable with these methods is far greater than with either HLA‐D typing or direct MLC testing.

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