Analysis details effects of HLA mismatch
GRAPEVINE, TEXAS—An analysis of more than 8000 patients provides insights regarding HLA disparity that may help optimize outcomes in individuals undergoing unrelated-donor hematopoietic stem cell transplant.
The study showed that a single allele- or antigen-level HLA mismatch (7/8) increased the risk for acute and chronic graft-vs-host disease (GVHD) and worsened survival rates.
However, there were no locus-specific effects on survival, and there was no impact of allele- vs antigen-level mismatch on survival.
In addition, patients with an 8/8 matched graft had an increased risk of acute GVHD if they had a DQB1 mismatch or a DPB1 mismatch. DPB1 mismatch also decreased the risk of relapse, and nonpermissive DPB1 mismatch was associated with worse survival.
“Thus, we believe that consideration of DPB1 in donor selection may permit skewing toward donors with permissive DPB1 mismatch and may improve outcomes,” said study investigator Joseph Pidala, MD, of the H. Lee Moffitt Cancer Center in Tampa, Florida.
He presented these findings at the 2014 BMT Tandem Meetings as abstract 5, which was designated one of the meeting’s “Best Abstracts.”
Patient characteristics
Dr Pidala and his colleagues evaluated data from 8003 adult and pediatric patients who had undergone their first myeloablative, unrelated transplant between 1999 and 2011. The patients had been diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, or myelodysplastic syndrome.
Patients and their donors had high-resolution typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1. Most cases were 8/8 matched (n=5449), followed by 7/8 (n=2071) and 6/8 (n=483).
“Those with a greater extent of HLA mismatch were younger, less likely to be Caucasian, they differed according to disease indication for transplant, and had a greater proportion of advanced disease stage,” Dr Pidala noted.
“Additionally, those with a greater extent of HLA mismatch were more likely to receive bone marrow grafts in comparison to peripheral blood, total body irradiation, and also to receive in vivo T-cell depletion.”
Furthermore, there was a declining proportion of 6/8 match over time. It decreased from 49% (1999-2002) to 37% (2003-2006) to 14% (2007-2011).
Effects of HLA mismatch
In all analyses, the researchers considered findings significant if the P value was less than 0.01.
Compared to an 8/8 matched graft, receiving a 7/8 graft was significantly associated with an increase in acute grade 2-4, acute grade 3-4, and chronic GVHD; higher transplant-related mortality (TRM); lower disease-free survival (DFS) among patients with early stage or intermediate (but not advanced) disease; and lower overall survival (OS) regardless of disease stage.
Receiving a 6/8 graft was significantly associated with an increase in acute grade 2-4 and 3-4 GVHD, increased TRM, decreased DFS (early stage or intermediate disease), and decreased OS (early stage or intermediate disease).
“In no cases did we find [that mismatch had] an impact on the incidence of primary disease relapse,” Dr Pidala said. “Comparing 7/8 to 6/8 cases, we found that those with 7/8 had improved transplant-related mortality and disease-free and overall survival [only] in the context of early stage disease.”
The team also confirmed these findings in an analysis of 5846 unique cases. In this cohort, 2528 patients were 8/8 matched, 882 were 7/8, and 157 were 6/8.
Locus-specific effects
Mismatch at HLA-A (n=743) was significantly associated with an increase in acute grade 2-4/3-4 and chronic GVHD, increased TRM, decreased DFS, and decreased OS.
Mismatch at HLA-B (n=345) was significantly associated with an increase in grade 2-4/3-4 acute GHVD, chronic GVHD, and TRM. And mismatch at HLA-C (n=766) was significantly associated with an increase in acute grade 3-4 GVHD and TRM and a decrease in DFS and OS.
