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Genomic risk factors and biomarkers as predictors of GvHD after haematopoietic stem cell transplantation

Lookup NU author(s): Dr Kim Pearce, Dr Shaheda Ahmed, Jean Norden, Dr Xiao Wang, Dr Udo Holtick, Professor Anne Dickinson

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Abstract

Introduction: In this study we propose a risk score to predict acute and/or chronic GvHD utilising clinical and genetic/biomarker variables. Methods Selected clinical variables were initially summed and an association was found between clinical risk score and outcome. Further potential genetic/biomarker predictors were additionally evaluated with a view to establishing if sensitivity and specificity could be improved. Results: In a cohort consisting of 442 HLA-matched sibling patient and donor pairs where the transplants were non T cell depleted, a strong association existed between clinical risk score and both the incidence of acute GvHD II-IV and chronic GvHD. Further investigation revealed that the donor IL10 haplotype ATA/ACC (rs1800872, rs1800871 and rs1800896), donor glucocorticoid receptor haplotype (rs6198, rs33389 and rs33388) ACA and recipient IL 10-592 SNP Any A (rs1800872) improved the goodness of fit when viewed in association with the clinical risk score for acute GvHD II-IV; no such genetic factors were found when modelling chronic GvHD but donor IL 4 Any T (rs2243250) did show a strong univariate association. It was established that the association between outcome and clinical risk score was still strong in a full cohort comprising of T cell replete and depleted patients (HLA matched siblings and unrelated donors). However, the association between the genetic factors and outcome was weaker. Specific biomarkers (CXCL10, CXCL11, IL-33 and BAFF) were therefore assessed as alternatives to genetic factors in a smaller cohort. It was found that BAFF (recorded at 14 days post transplant) was an additional predictor for acute GvHD II-IV and, when added to a model containing the clinical risk score, sensitivity improved from 64% to 86% and specificity from 69% to 81% (N=30). Conclusion: Preliminary analysis has demonstrated that a statistical model can be constructed to predict occurrence of acute GvHD II-IV and chronic GvHD using clinical factors. Genetic factors could improve the goodness of fit of a model when viewed alongside a clinical risk score, however, we were unable to confirm the result in a second cohort. As an alternative to genetic factors, biomarkers could, however, be used as additional predictors. Further work is under way to validate the results in independent cohorts.


Publication metadata

Author(s): Pearce KF, Ahmed S, Norden J, Collin MP, Wang XN, Cornelissen JJ, Wolff D, Aubano A, Holtick U, Scheid C, Socie G, Greinix H, Holler E, Dickinson AM

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: 39th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT)

Year of Conference: 2013

Pages: S410-S410

ISSN: 0268-3369

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bmt.2013.23

DOI: 10.1038/bmt.2013.23

Notes: Abstract no: P1137 Online ISSN: 1476-5365

Series Title: Bone Marrow Transplantation


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