Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: matching for transplants from related haploidentical donors.
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-DR region by HTC typing. Donor antirecipient 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.
Mickelson
E M
EM
Fred Hutchinson Cancer Research Center, Seattle, WA.
Guthrie
L A
LA
Etzioni
R
R
Anasetti
C
C
Martin
P J
PJ
Hansen
J A
JA
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000401:mortality; D002648:Child; D005069:Evaluation Studies as Topic; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D006684:HLA-DR Antigens / Q000032:analysis* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics*; D006402:Hematologic Diseases / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D014019:Tissue Donors; D009927:Tissue and Organ Procurement; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D006684:HLA-DR Antigens