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Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time‐series gene expression profiling
Author(s) -
Yeoh Allen E.J.,
Li Zhenhua,
Dong Difeng,
Lu Yi,
Jiang Nan,
Trka Jan,
Tan Ah Moy,
Lin Hai Peng,
Quah Thuan Chong,
Ariffin Hany,
Wong Limsoon
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15252
Subject(s) - medicine , minimal residual disease , oncology , cumulative incidence , hazard ratio , confidence interval , gene expression profiling , bone marrow , gene expression , gene , cohort , biology , genetics
Summary Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under‐ or over‐treatment. We hypothesized that time‐series gene expression profiles ( GEP s) 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 .