Human Leukocyte Antigen (HLA) DR15 Is Associated with Reduced Incidence of Acute GvHD in HLA-Matched Allogeneic HSCT but Does Not Impact Survival.

HLA DR 15 is found more frequently in patients with bone marrow failure syndromes and is associated with response to immunosuppression. This suggests that HLA DR15 may preferentially present immunodominant myeloid antigens or that HLA DR15 positive cells may be more sensitive to immunosuppression. We investigated the role of HLA DR15 on graft-versus-leukemia effect and graft-versus-host disease (GVHD) in HLA-matched HSCTs performed for myeloid malignancies. We performed a retrospective review of 109 consecutive related and 42 consecutive unrelated allogeneic HSCT patients treated between 1991 and 2003 at Roswell Park Cancer Institute to investigate the influence of HLA DR15 on overall survival (OS), progression-free survival (PFS) and the incidence of grade 2–4 acute GVHD. HLA DR15 was determined by either molecular (n=92) or serologic (n=59) methods. The proportion of patients with one or two HLA DR15 alleles was 21% (32/151) which is similar to the general Caucasian population. Patient characteristics included: AML (n=74), CML (n=59), and MDS (n=18); median age 42 years (range 11–62); Males (n=93), Females (n=58); Caucasian (>95%); TBI-containing conditioning regimens (n=130); Busulfan + Cyclophosphamide (n=19), Busulfan + TBI (n=27), Cyclophosphamide + TBI (n=11), Etoposide + Cyclophosphamide + TBI (n=84), or other combinations (n=10). There was no difference in OS between the HLA DR15 positive versus negative groups in any disease or donor relation subgroups. There was no significant difference in PFS between the HLA DR15 positive and negative groups, however a trend toward late relapses after three years was observed in the HLA DR15 positive group. The HLA DR15 positive group experienced a significantly lower incidence of acute GVHD grade 2–4: 22% versus 41%, p=0.045. There was no difference between the HLA DR15 positive versus negative groups with respect to conditioning regimen, use of TBI or GVHD prophylaxis regimen. We are currently expanding this study to include a larger cohort from other centers. These results suggest that HLA DR15 may function as a surrogate for an altered response to the immunosuppression induced by GvHD prophylaxis. If these results are confirmed, this would be the first association between a specific HLA antigen and GvHD development, thus suggesting the need for studying GvHD prophylaxis modification based on specific HLA antigens.