An association between human leucocyte antigen alleles and acute and chronic graft‐versus‐host disease after allogeneic haematopoietic stem cell transplantation

• Published in: British journal of haematology Vol. 119; no. 3; pp. 751 - 759
• Main Authors: Remberger, Mats, Persson, Ulla, Hauzenberger, Dan, Ringdén, Olle
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2002; Blackwell; Blackwell Publishing Ltd
• Subjects: Acute Disease; Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Child; Child, Preschool; Chronic Disease; Female; Gene Frequency; Graft vs Host Disease - immunology; graft‐versus‐host disease; haematopoietic stem‐cell transplant; Hematologic Diseases - immunology; Hematologic Diseases - therapy; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; HLA Antigens - genetics; human leucocyte antigen; Humans; Infant; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Risk Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Immunopathology; HLA-System; Acute; Stem cell; Hematopoietic cell; Homograft; Graft versus host reaction; Hemopathy; Genetic determinism; Blood; Chronic; Treatment; human leucocyte antigen; haematopoietic stem-cell transplant; Risk factor; Bone marrow; Graft; Genetics; Complication; graft-versus-host disease
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03924.x

The association between various human leucocyte antigen (HLA) alleles and the occurrence of acute and chronic graft‐versus‐host disease (GVHD) was evaluated in 493 haematopoietic stem‐cell transplant (HSCT) patients with HLA identical sibling donors. There were 307 men and 186 women with a median age of 30 years (0·2–77). Most of the patients had a haematological malignancy and received total body irradiation or busulphan combined with cyclophosphamide as conditioning before transplantation. GVHD prophylaxis consisted of monotherapy with methotrexate (MTX) or cyclosporin (CsA) in 118 patients, MTX + CsA in 323, T‐cell depletion in 28 and other combinations in 24. In total, 84 patients (17%) received a peripheral blood stem‐cell graft, whereas the rest received bone marrow. The cumulative incidence of acute GVHD grades II–IV was 20%, and chronic GVHD 46%. In the multivariate analysis, HLA‐A10 (OR 2·14, CI 1·04–4·41, P = 0·03) and HLA‐B7 (OR 1·80, CI 1·04–3·12, P = 0·03) correlated with an increased risk of acute GVHD grades II‐IV. We also found an association between HLA‐B27 (RR 0·60, CI 0·37–0·95, P = 0·04) and a lower incidence of chronic GVHD. These HLA alleles were independent of other known risk factors for acute or chronic GVHD, as shown by multivariate analysis. These results show that major histocompatibility comlex (MHC) alleles may influence the incidence of GVHD in HSCT with HLA identical sibling donors.