TY - JOUR
T1 - HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies
AU - Battiwalla, Minoo
AU - Ellis, Kristin
AU - Li, Peigang
AU - Pavletic, Steven Z.
AU - Akpek, Gorgun
AU - Hematti, Peiman
AU - Klumpp, Thomas R.
AU - Maziarz, Richard T.
AU - Savani, Bipin N.
AU - Aljurf, Mahmoud D.
AU - Cairo, Mitchell S.
AU - Drobyski, William R.
AU - George, Biju
AU - Hahn, Theresa
AU - Khera, Nandita
AU - Litzow, Mark R.
AU - Loren, Alison W.
AU - Saber, Wael
AU - Arora, Mukta
AU - Urbano-Ispizua, Alvaro
AU - Cutler, Corey
AU - Flowers, Mary E.D.
AU - Spellman, Stephen R.
N1 - Funding Information:
Financial disclosure: This work was supported by the National Institute of Health (NIH) intramural research programs of the NHLBI and NCI. CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) ; a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI ; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-10-1-0204 and N00014-1-1-0339 from the Office of Naval Research ; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc.
PY - 2012/8
Y1 - 2012/8
N2 - The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.
AB - The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.
KW - DR15
KW - GVHD
KW - Graft-versus-lymphoma
KW - Hematopoietic stem cell transplantation (HSCT)
KW - Survival
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U2 - 10.1016/j.bbmt.2012.02.011
DO - 10.1016/j.bbmt.2012.02.011
M3 - Article
C2 - 22414493
AN - SCOPUS:84863996073
SN - 1083-8791
VL - 18
SP - 1302
EP - 1308
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -