title: Cytotoxic T-lymphocyte antigen-4 single nucleotide polymorphisms are not associated with outcomes after unrelated donor transplantation: a center for international blood and marrow transplant research analysis.
abstract: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays an essential role in T cell homeostasis by restraining immune responses. AG and GG genotypes of donor CTLA-4 SNP rs4553808 in patients after unrelated donor hematopoietic stem cell transplantations (HSCT) have been shown to be an independent predictor of inferior relapse-free survival (RFS) and overall survival (OS) compared with those with the AA genotype, in single-center studies. We tested the hypothesis that SNP rs4553808 is associated with RFS, OS, nonrelapse mortality (NRM) and the cumulative incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in adults with acute myeloid leukemia and advanced myelodysplastic syndrome undergoing a first 8/8 or 7/8 HLA-matched unrelated donor HSCT. Multivariable analysis adjusting for relevant donor and recipient characteristics showed no significant association between SNP rs4553808 and OS, RFS, NRM, and incidence of acute and chronic GVHD. An exploratory analysis of other CTLA-4 SNPs, as well as studying the interaction with antithymocyte globulin, also demonstrated no significant associations. Our results indicate that CTLA-4 SNPs are not associated with HSCT outcomes.
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee. Electronic address: salyka.sengsayadeth@vanderbilt.edu.
authors.forename: Salyka
authors.initials: S
authors.lastname: Sengsayadeth
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Center for International Blood & Marrow Transplant Research, National Marrow Donor Program, Minneapolis, Minnesota.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for International Blood & Marrow Transplant Research, National Marrow Donor Program, Minneapolis, Minnesota.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Haagenson
authors.affiliation: Center for International Blood & Marrow Transplant Research, National Marrow Donor Program, Minneapolis, Minnesota.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Department of Pathology, Stanford Medical School, Stanford University, Stanford, California.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernandez Viña
authors.affiliation: Germany National Bone Marrow Registry, Ulm, Germany.
authors.forename: Carlheinz R
authors.initials: CR
authors.lastname: Muller
authors.affiliation: Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Section of Hematology and Stem Cell Transplantation, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: Cytotoxic T-lymphocyte antigen-4 (CTLA-4); Hematopoietic stem cell transplantation; Single nucleotide polymorphisms (SNPs)