title: Predicting survival using clinical risk scores and non-HLA immunogenetics.
abstract: Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Göttingen, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Balavarca
authors.affiliation: Department of Haematological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: K
authors.initials: K
authors.lastname: Pearce
authors.affiliation: Department of Haematological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: J
authors.initials: J
authors.lastname: Norden
authors.affiliation: Department of Haematological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: M
authors.initials: M
authors.lastname: Collin
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.affiliation: Department of Cellular and Molecular Immunology, University Medical Center, Göttingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Dressel
authors.affiliation: Department of Haematology and Oncology, Klinikum Grosshadern, Medical Klinik III, Munich, Germany.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kolb
authors.affiliation: Department of Haematology, Division of Haematology, Medical University of Graz, Graz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Greinix
authors.affiliation: Department of Haematology, Immunology and Oncology, AP-HP, Saint Louis Hospital, Hematology Transplantation, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Socie
authors.affiliation: Departement d'Immunologie, Université Paris Diderot, INSERM UMRS-940, AP-HP, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Toubert
authors.affiliation: Department of Bone Marrow Transplantation, EUROCORD, St Louis Hospital, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Rocha
authors.affiliation: Department of Bone Marrow Transplantation, EUROCORD, St Louis Hospital, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.affiliation: Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Hromadnikova
authors.affiliation: Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Sedlacek
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wolff
authors.affiliation: Department I of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Holtick
authors.affiliation: Department of Haematological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A
authors.initials: A
authors.lastname: Dickinson
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Göttingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bickeböller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002423:Cause of Death; D002648:Child; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006086:Graft vs Host Disease / Q000401:mortality; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006648:Histocompatibility; D006801:Humans; D007239:Infections / Q000401:mortality; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D017472:Receptors, Interleukin-1 / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D019172:Transplantation Conditioning / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D016753:Interleukin-10