Predicting survival using clinical risk scores and non-HLA immunogenetics
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26214138
DOI
10.1038/bmt.2015.173
PII: bmt2015173
Knihovny.cz E-resources
- MeSH
- Estrogen Receptor alpha genetics MeSH
- Allografts MeSH
- Child MeSH
- Adult MeSH
- Genotype MeSH
- Haplotypes MeSH
- Hematologic Neoplasms mortality therapy MeSH
- Histocompatibility MeSH
- Risk Assessment methods MeSH
- Infections mortality MeSH
- Interleukin-10 genetics MeSH
- Interleukin-6 genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Membrane Glycoproteins genetics MeSH
- Adolescent MeSH
- Multiple Organ Failure mortality MeSH
- Follow-Up Studies MeSH
- Graft vs Host Disease mortality MeSH
- Cause of Death MeSH
- Transplantation Conditioning adverse effects MeSH
- Prognosis MeSH
- Proportional Hazards Models MeSH
- Receptors, Interleukin-1 genetics MeSH
- Aged MeSH
- Hematopoietic Stem Cell Transplantation mortality MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Estrogen Receptor alpha MeSH
- ESR1 protein, human MeSH Browser
- IL10 protein, human MeSH Browser
- IL6 protein, human MeSH Browser
- Interleukin-10 MeSH
- Interleukin-6 MeSH
- Membrane Glycoproteins MeSH
- Receptors, Interleukin-1 MeSH
- TIRAP protein, human MeSH Browser
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.
Departement d'Immunologie Université Paris Diderot INSERM UMRS 940 AP HP Paris France
Department 1 of Internal Medicine University of Cologne Cologne Germany
Department of Bone Marrow Transplantation EUROCORD St Louis Hospital Paris France
Department of Cellular and Molecular Immunology University Medical Center Göttingen Germany
Department of Genetic Epidemiology University Medical Center Göttingen Germany
Department of Haematology and Oncology Klinikum Grosshadern Medical Klinik 3 Munich Germany
Department of Haematology Division of Haematology Medical University of Graz Graz Austria
Department of Hematology and Oncology University of Regensburg Regensburg Germany
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