title: Analysis of non-HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia.
abstract: BACKGROUND
  Allogeneic hematopoietic cell transplantation is the main curative therapy for patients with chronic myeloid leukemia who do not respond to tyrosine kinase inhibitors. It has been proposed that non-human leukocyte antigen gene polymorphisms influence outcome after hematopoietic cell transplantation and could be used alongside traditional patient-donor and transplant characteristics to create a recipient risk profile associated with allogeneic hematopoietic cell transplantation.
  
  
  METHODS
  A previous study from the European Group for Blood and Marrow Transplantation showed that the absence of recipient tumor necrosis factor receptor II, absence of donor interleukin 10 ATA/ACC and presence of donor interleukin 1 receptor antagonist allele 2 genotypes were associated with decreased survival and increased non-relapse mortality in adult patients with chronic myeloid leukemia undergoing myeloablative human leukocyte antigen-identical sibling transplantation. To explore these associations in unrelated donor transplantation, these polymorphisms were genotyped in 383 adult patients with chronic myeloid leukemia who underwent hematopoietic cell transplantation from unrelated donors matched for 10/10 human leukocyte antigens.
  
  
  RESULTS
  The polymorphisms were not associated with overall survival, non-relapse mortality, relapse or acute graft-versus-host disease in the unrelated donor cohort. Comparison of the unrelated donor and human leukocyte antigen-identical sibling cohorts showed differences in survival and clinical characteristics.
  
  
  CONCLUSIONS
  We did not confirm that non-human leukocyte antigen polymorphisms were associated with outcomes in myeloablative unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia, possibly because of the strong association between clinical variables and outcome which masked more subtle genetic effects.
authors.affiliation: Haematological Sciences, Institute of Cellular Medicine, William Leech Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. k.f.pearce@ncl.ac.uk
authors.forename: Kim F
authors.initials: KF
authors.lastname: Pearce
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Effie W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: Jean
authors.initials: J
authors.lastname: Norden
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Collin
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.forename: Shelagh A
authors.initials: SA
authors.lastname: Lowerson
authors.forename: Stella
authors.initials: S
authors.lastname: Davies
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000276:immunology; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D006680:HLA Antigens; D019653:Myeloablative Agonists; D053574:Receptors, Interleukin-1 Type II; D047889:Receptors, Tumor Necrosis Factor, Type II; D016753:Interleukin-10