Predicting survival using clinical risk scores and non-HLA immunogenetics

Y. Balavarca; K. Pearce; J. Norden; M. Collin; G. Jackson; E. Holler; R. Dressel; H. J. Kolb; H. Greinix; G. Socie; A. Toubert; V. Rocha; E. Gluckman; I. Hromadnikova; P. Sedlacek; D. Wolff; U. Holtick; A. Dickinson; H. Bickeböller

doi:10.1038/bmt.2015.173

Predicting survival using clinical risk scores and non-HLA immunogenetics

Y. Balavarca, K. Pearce, J. Norden, M. Collin, G. Jackson, E. Holler, R. Dressel, H. J. Kolb, H. Greinix, G. Socie, A. Toubert, V. Rocha, E. Gluckman, I. Hromadnikova, P. Sedlacek, D. Wolff, U. Holtick, A. Dickinson, H. Bickeböller

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Pages (from-to)	1445-1452
Number of pages	8
Journal	Bone Marrow Transplantation
Volume	50
Issue number	11
DOIs	https://doi.org/10.1038/bmt.2015.173
State	Published - 1 Nov 2015
Externally published	Yes

Access to Document

10.1038/bmt.2015.173

Cite this

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., & Bickeböller, H. (2015). Predicting survival using clinical risk scores and non-HLA immunogenetics. Bone Marrow Transplantation, 50(11), 1445-1452. https://doi.org/10.1038/bmt.2015.173

@article{391b744d7f9b41be84453b77cb6d74df,

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.",

author = "Y. Balavarca and K. Pearce and J. Norden and M. Collin and G. Jackson and E. Holler and R. Dressel and Kolb, \{H. J.\} and H. Greinix and G. Socie and A. Toubert and V. Rocha and E. Gluckman and I. Hromadnikova and P. Sedlacek and D. Wolff and U. Holtick and A. Dickinson and H. Bickeb{\"o}ller",

year = "2015",

month = nov,

day = "1",

doi = "10.1038/bmt.2015.173",

language = "English",

volume = "50",

pages = "1445--1452",

journal = "Bone Marrow Transplantation",

issn = "0268-3369",

publisher = "Springer Nature",

number = "11",

}

Balavarca, Y, Pearce, K, Norden, J, Collin, M, Jackson, G, Holler, E, Dressel, R, Kolb, HJ, Greinix, H, Socie, G, Toubert, A, Rocha, V, Gluckman, E, Hromadnikova, I, Sedlacek, P, Wolff, D, Holtick, U, Dickinson, A & Bickeböller, H 2015, 'Predicting survival using clinical risk scores and non-HLA immunogenetics', Bone Marrow Transplantation, vol. 50, no. 11, pp. 1445-1452. https://doi.org/10.1038/bmt.2015.173

TY - JOUR

T1 - Predicting survival using clinical risk scores and non-HLA immunogenetics

AU - Balavarca, Y.

AU - Pearce, K.

AU - Norden, J.

AU - Collin, M.

AU - Jackson, G.

AU - Holler, E.

AU - Dressel, R.

AU - Kolb, H. J.

AU - Greinix, H.

AU - Socie, G.

AU - Toubert, A.

AU - Rocha, V.

AU - Gluckman, E.

AU - Hromadnikova, I.

AU - Sedlacek, P.

AU - Wolff, D.

AU - Holtick, U.

AU - Dickinson, A.

AU - Bickeböller, H.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947029828&partnerID=8YFLogxK

U2 - 10.1038/bmt.2015.173

DO - 10.1038/bmt.2015.173

M3 - Article

C2 - 26214138

AN - SCOPUS:84947029828

SN - 0268-3369

VL - 50

SP - 1445

EP - 1452

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 11

ER -

Predicting survival using clinical risk scores and non-HLA immunogenetics

Abstract

Access to Document

Other files and links

Fingerprint

Cite this