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Blood, 1 May 2007, Vol. 109, No. 9, pp. 4064-4070.
Prepublished online as a Blood First Edition Paper on January 3, 2007; DOI 10.1182/blood-2006-06-032193.


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Submitted June 28, 2006
Accepted December 23, 2006

HLA mismatching within or outside of cross reactive groups (CREG) is associated with similar outcomes after unrelated hematopoietic stem cell transplant

Judith A. Wade, Carolyn Katovich Hurley, Steven K. Takemoto, John Thompson, Stella M. Davies, Thomas C. Fuller, Glenn Rodey, Dennis L. Confer, Harriet Noreen, Michael Haagenson, Fangyu Kan, John Klein, Mary Eapen, Stephen Spellman*, and Craig Kollman

Department of Surgery, University of Toronto, Toronto, Canada
Department of Oncology, Georgetown University, Washington, DC, United States
Department of Internal Medicine, St. Louis University, St. Louis, MO, United States
Department of Medicine, University of Kentucky, Lexington, KY, United States
Department of Hematology/Oncology, Cincinatti Childrens Hospital Medical Center, Cincinnati, OH, United States
Department of Pathology, University of Utah, Salt Lake City, UT, United States
Department of Pathology, Baylor College of Medicine, Houston, TX, United States
National Marrow Donor Program, Minneapolis, MN, United States
Immunology Laboratory, University of Minnesota Medical Center, Fairview, Minneapolis, MN, United States
Center for International Blood and Marrow Transplantation Research, Minneapolis, MN, United States
Center for International Blood and Marrow Transplantation Research, Milwaukee, WI, United States
Jaeb Center for Health Research, Tampa, FL, United States

* Corresponding author; email: sspellma{at}nmdp.org.

The National Marrow Donor Program® maintains a registry of volunteer donors for patients in need of a hematopoietic stem cell transplant. Strategies for selecting a partially HLA-mismatched donor vary when a full match cannot be identified. Some transplant centers limit the selection of mismatched donors to those sharing mismatched antigens within HLA-A, -B cross reactive groups (CREG). To assess whether an HLA mismatch within a CREG group ("minor") may result in better outcome than a mismatch outside CREG groups ("major"), we analyzed validated outcomes data from 2709 bone marrow and peripheral blood stem cell transplants. 396 pairs (15%) were HLA-DRB1 allele matched but had an antigen-level mismatch at HLA-A or -B. Univariate and multivariate analyses of engraftment, graft-versus-host disease and survival showed that outcome is not significantly different between "minor" and "major" mismatches (p=0.47 from the log-rank test for Kaplan-Meier survival). However, HLA-A, -B, -DRB1 allele matched cases had significantly better outcome than mismatched cases (p<0.0001). For patients without an HLA match, the selection of a CREG compatible donor as tested does not improve outcome


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