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HLA-Mismatch Is Associated with Worse Outcomes after Myeloablative Conditioning and Unrelated Donor Hematopoietic Cell Transplantation: A Cibmtr Analysis

Track: BMT Tandem "Scientific" Meeting
Friday, February 28, 2014, 4:45 PM-6:30 PM
Texas B+D (Gaylord Texan)
Joseph Pidala, MD, MS , H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Stephanie J. Lee, MD, MPH , Fred Hutchinson Cancer Research Center, Seattle, WA
Stephen R Spellman, MBS , Immunobiology and Observational Research, Center for International Blood and Marrow Transplant Research, Minneapolis, MN
Hailin Wang, MPH , CIBMTR, Medical College of Wisconsin, Milwaukee, WI
Kwang Woo Ahn, PhD , Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI
Mahmoud D. Aljurf, MD, MPH , King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Medhat Askar, MD, PhD , Cleveland Clinic, Cleveland, OH
Jason Dehn, MPH , National Marrow Donor Program, Minneapolis, MN
Marcelo A. Fernandez Viña, PhD , Stanford Hospital and Clinics, Stanford, CA
Alois Gratwohl, MD , Hematology & Stem Cell Transplant Unit, University Hospital Basel, Basel, Switzerland
Vikas Gupta, MD , Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada
Rabi Hanna, MD , Cleveland Clinic, Cleveland, OH
Carolyn K. Hurley, PhD , Georgetown University Hospital, Washington, DC
Yoshihiro Inamoto, MD , Fred Hutchinson Cancer Research Center, Seattle, WA
Adetola A. Kassim, MD, MS , Vanderbilt University Medical Center, Nashville, TN
Taiga Nishihori, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Machteld Oudshoorn, PhD , Europdonor Foundation, Leiden University Medical Centre, Leiden, Netherlands
Effie W. Petersdorf, MD , Fred Hutchinson Cancer Research Center, Seattle, WA
Vinod K. Prasad, MD , Pediatric BMT Program, Duke University Medical Center, Durham, NC
Wael Saber, MD, MS , CIBMTR, Medical College of Wisconsin, Milwaukee, WI
Kirk R. Schultz, MD , British Columbia's Children's Hospital, Vancouver, BC, Canada
William A. Wood, MD, MPH , University of North Carolina Hospitals, Chapel Hill, NC
Jan Storek, MD, PhD , Tom Baker Cancer Centre/Foothills Hospital, Calgary, AB, Canada
Ann E. Woolfrey, MD , Fred Hutchinson Cancer Research Center, Seattle, WA
Claudio Anasetti, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Audio File Recorded Presentation

Background: Previous studies have demonstrated the adverse impact of HLA mismatch on the outcome of myeloablative conditioning and unrelated donor allogeneic hematopoietic cell transplantation (HCT). These have had limited power in certain sub-groups, and do not reflect changes in HCT utilization and technology.

Methods: Included were adult and pediatric patients who had undergone first myeloablative unrelated bone marrow or peripheral blood HCT for AML, ALL, CML, or MDS between 1999 and 2011. Patient and donor had high resolution typing for HLA-A, B, C, DRB1, DQB1, and DPB1. Study outcomes included overall survival (OS), disease-free survival (DFS), treatment-related mortality (TRM), malignancy relapse, acute graft vs. host disease (GVHD), and chronic GVHD. The primary analysis tested the impact of mismatch at HLA-A, B, C and DRB1. Secondary analyses examined HLA locus-specific effects, allele vs. antigen mismatch, and the impact of DPB1 and DQB1 mismatch. Additional patient, disease, and HCT variables were considered in multivariate analyses. A p value < 0.01 was considered significant.

Results: Of the study population (n=8,003), cases were 8/8 (n=5,449), 7/8 (n=2,071), or 6/8 (n=483) matched. Median follow up for surviving patients was 49 (3-151) months. The study population was 88% Caucasian, 67% KPS 90-100, 77% acute leukemia and only 14% CML, 56% peripheral blood, and 43% non-TBI myeloablative conditioning. Of the total, 20% were from 1999-2002, 32% 2003-2006, and 49% from 2007-2011. In the primary analysis, HLA mismatch (6-7/8) conferred significantly increased risk for grade II-IV and III-IV acute GVHD, chronic GVHD, and TRM, and worsened DFS and OS compared to HLA matched cases (8/8). Malignancy relapse was not affected by HLA mismatch at A, B, C, or DRB1. The 6/8 cases had significantly worse TRM than 7/8 cases. The adverse impact of HLA mismatch on OS was greatest among those with early or intermediate stage disease. Single mismatch at HLA-A, B, and C increased the risk for acute GVHD, TRM, and worsened OS. While single antigen mismatch at HLA-B increased risk for grade II-IV acute GVHD over single allele mismatch at –B, no other differences were detected between allele or antigen mismatch. Among 8/8 matched cases, DPB1 mismatch was associated with increased grade II-IV and III-IV acute GVHD and decreased relapse, and DQB1 mismatch was associated with increased grade II-IV acute GVHD; these effects were not observed among 7/8 cases. DPB1 and DQB1 mismatch among 7/8 or 8/8 cases had no effect on OS or DFS.

Conclusions: Despite improvements in survival after unrelated donor HCT over time, donor-recipient HLA disparity remains a major source of GVHD and mortality.

Disclosures:
Nothing To Disclose
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