Limits of HLA mismatching in unrelated hematopoietic cell transplantation

• Published in: Blood Vol. 104; no. 9; pp. 2976 - 2980
• Main Authors: Petersdorf, Effie W., Anasetti, Claudio, Martin, Paul J., Gooley, Ted, Radich, Jerald, Malkki, Mari, Woolfrey, Ann, Smith, Anajane, Mickelson, Eric, Hansen, John A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-11-2004; The Americain Society of Hematology
• Subjects: Alleles; Biological and medical sciences; Female; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Histocompatibility - genetics; Histocompatibility Testing; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Myeloablative Agonists - therapeutic use; Risk; Survival Analysis; Transplantation Immunology; Transplantation, Homologous; Treatment Outcome; Human; Incompatibility; HLA-System; Unrelated donor; Stem cell; Major histocompatibility system; Class II histocompatibility antigen; Hematopoietic cell; Homograft; Malignant hemopathy; Myeloproliferative syndrome; Chronic; Treatment; Chronic myelocytic leukemia; Graft; Class I histocompatibility antigen
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-04-1674

HLA matching between the donor and recipient improves the success of unrelated hematopoietic cell transplantation (HCT). Matched donors are available for only a minority of patients. Further information is needed to evaluate the limits of HLA mismatching. We examined the association of mortality with HLA-A, -B, -C, -DRB1, and -DQB1 mismatching in 948 patients who received a T-replete unrelated HCT for treatment of a marrow disorder. A single HLA allele or antigen mismatch was associated with increased mortality among patients with chronic myeloid leukemia (CML) within 2 years after diagnosis compared to patients with no HLA mismatch, but not among those with more advanced malignancy. In particular, a single HLA-C mismatch conferred increased risk of mortality compared to matches. There was a suggestion for increased mortality with multiple mismatches involving HLA-DQB1 compared to multiple mismatches not involving HLA-DQB1. Donors with a single HLA allele or antigen mismatch may be used for HCT when a fully matched donor is not available for patients with diseases that do not permit time for a lengthy search. Whenever possible, HLA-C mismatches should be avoided for patients with early stage CML, and HLA-DQB1 mismatches should be avoided for patients with multiple mismatches.