Yeoh, Allen Eng Juh and Li, Zhenhua and Dong, Difeng and Lu, Yi and Jiang, Nan and Trka, Jan and Tan, Ah Moy and Lin, Hai Peng and Quah, Thuan Chong and Ariffin, Hany and Wong, Lim Soon (2018) Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time-series gene expression profiling. British Journal of Haematology, 181 (5). pp. 653-663. ISSN 0007-1048, DOI https://doi.org/10.1111/bjh.15252.
Full text not available from this repository.Abstract
Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM-D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM-D8 patients had >3-fold increased risk of relapse compared to favourable ERM-D8 (5-year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10−3). ERM-D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03–16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM-D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10−3). We conclude that our novel metric – ERM-D8 – based on time-series GEP after 8 days of remission-induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
| Item Type: | Article |
|---|---|
| Funders: | Singapore NMRC Clinician Scientist Investigator Award (NMRC/CSA/0053/2013 and NMRC/CSA/003/2008), VIVA Foundation of Children with Cancer, GOH Foundation and Children’s Cancer Foundation |
| Uncontrolled Keywords: | acute lymphoblastic leukaemia; effective response metric; gene expression; relapse; time-series |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Feb 2019 04:25 |
| Last Modified: | 13 Feb 2019 04:25 |
| URI: | http://eprints.um.edu.my/id/eprint/20281 |
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