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Lookup NU author(s): Dr Kim PearceORCiD, Dr Shaheda Ahmed, Jean Norden, Professor Matthew CollinORCiD, Dr Xiao WangORCiD, Dr Udo Holtick, Professor Anne Dickinson
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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.
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
