A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children

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dc.contributor.authorSutton, R.
dc.contributor.authorVenn, N.
dc.contributor.authorLaw, T.
dc.contributor.authorBoer, J.
dc.contributor.authorTrahair, T.
dc.contributor.authorNg, A.
dc.contributor.authorDen Boer, M.
dc.contributor.authorDissanayake, A.
dc.contributor.authorGiles, J.
dc.contributor.authorDalzell, P.
dc.contributor.authorMayoh, C.
dc.contributor.authorBarbaric, D.
dc.contributor.authorRevesz, T.
dc.contributor.authorAlvaro, F.
dc.contributor.authorPieters, R.
dc.contributor.authorHaber, M.
dc.contributor.authorNorris, M.
dc.contributor.authorSchrappe, M.
dc.contributor.authorDalla Pozza, L.
dc.contributor.authorMarshall, G.
dc.date.issued2018
dc.description.abstractTo prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10-5 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001). We created a predictive model based on a risk score (RS) for deletions, MRD and NCI risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91% and 71%. The RS provided greater discrimination than MRD-based risk stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS, 91% OS). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL.
dc.description.statementofresponsibilityRosemary Sutton, Nicola C. Venn, Tamara Law, Judith M. Boer, Toby N. Trahair ... Tamas Revesz ... et al.
dc.identifier.citationBritish Journal of Haematology, 2018; 180(4):550-562
dc.identifier.doi10.1111/bjh.15056
dc.identifier.issn0007-1048
dc.identifier.issn1365-2141
dc.identifier.orcidRevesz, T. [0000-0003-2501-0259]
dc.identifier.urihttp://hdl.handle.net/2440/111743
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1009087
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1057746
dc.rights© 2017 John Wiley & Sons Ltd
dc.source.urihttps://doi.org/10.1111/bjh.15056
dc.subjectAcute lymphoblastic leukaemia; microdeletions; IKZF1; CRLF2; risk score.
dc.titleA risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children
dc.typeJournal article
pubs.publication-statusPublished

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