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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4560-4566.
Prepublished online as a Blood First Edition Paper on August 28, 2007; DOI 10.1182/blood-2007-06-095265.
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Submitted June 12, 2007
Accepted August 7, 2007
The importance of HLA-DPB1 in unrelated donor haematopoietic cell transplantation
Bronwen E Shaw*, Theodore A. Gooley, Mari Malkki, J Alejandro Madrigal, Ann B Begovich, Mary M Horowitz, Alois Gratwohl, Olle Ringden, Steven G.E. Marsh, and Effie W Petersdorf
Section of Haemato-Oncology, Royal Marsden Hosptial/Institute of Cancer Research, Surrey, United Kingdom
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Anthony Nolan Research Institute, London, United Kingdom
Roche Molecular Systems, Alameda, CA, United States
Center for International Blood & Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, United States
Hematology Department, University Hospital Basel, Basel, Switzerland
Division of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden
Royal Free & University College of London, London, United Kingdom
Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States
* Corresponding author; email: bshaw{at}doctors.org.uk.
Haematopoietic cell transplantation (HCT) from an HLA-A, -B, -C, -DRB1, -DQB1 allele-matched unrelated donor is a well recognised life-saving treatment modality for patients with haematological disorders. The morbidity and mortality from clinically significant acute graft-versus-host disease (aGVHD) remains a limitation. The extent to which transplant outcome may be improved with donor matching for HLA-DP is not well defined. The risks of aGVHD, relapse and mortality associated with HLA-DPB1 allele mismatching were determined in 5929 patients who received a myeloablative HCT from an HLA-A, -B, -C, -DRB1, -DQB1 matched or mismatched donor. There was a statistically significantly higher risk of both grade II-IV aGVHD (OR=1.33, p<0.0001) and grade III-IV aGVHD (OR=1.26, p=0.0007) after HCT from an HLA-DPB1 mismatched donor compared to a matched donor. The increased risk of aGVHD was accompanied by a statistically significantly decrease in disease relapse (HR=0.82, p=0.01). HLA-DPB1 functions as a classical transplantation antigen. The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. Knowledge of the DPB1 matching status prior to transplant will aid in more precise risk stratification for the individual patient.will aid in more precise risk stratification for the individual patient.
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