Balavarca, Y., Pearce, K., Norden, J., Collin, M., Jackson, G., Holler, E., Dressel, R., Kolb, H-J, Greinix, H., Socie, G., Toubert, A., Rocha, V., Gluckman, E., Hromadnikova, I., Sedlacek, P., Wolff, D., Holtick, U., Dickinson, A. and Bickeboeller, H. (2015). Predicting survival using clinical risk scores and non-HLA immunogenetics. Bone Marrow Transplant., 50 (11). S. 1445 - 1453. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5365

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Balavarca, Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearce, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Norden, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collin, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jackson, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holler, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dressel, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolb, H-JUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greinix, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Socie, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toubert, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rocha, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gluckman, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hromadnikova, I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sedlacek, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolff, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holtick, U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dickinson, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bickeboeller, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-387482
DOI: 10.1038/bmt.2015.173
Journal or Publication Title: Bone Marrow Transplant.
Volume: 50
Number: 11
Page Range: S. 1445 - 1453
Date: 2015
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5365
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; GENE POLYMORPHISM; PROMOTER POLYMORPHISM; IN-VITRO; MESSENGER-RNA; RECEPTOR; IDENTIFICATION; ASSOCIATION; EXPRESSIONMultiple languages
Biophysics; Oncology; Hematology; Immunology; TransplantationMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38748

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