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Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia

Lookup NU author(s): Professor Julie Irving, Dr Amir EnshaeiORCiD, Dr Amy Erhorn, Lynne Minto, Claire Schwab, Elizabeth Matheson, Alysia Davies, Professor Christine Harrison FRCPath FMedSci, Professor Anthony MoormanORCiD

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Abstract

Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility atinitial diagnosis. However, the genetic landscape and its clinical utility at relapse is less wellunderstood and has not been studied comprehensively. We analysed cytogenetic data from 427children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also wescreened 238 patients with a marrow relapse for selected copy number alterations (CNA) andmutations. Cytogenetic risk groups were predictive of outcome post-relapse and survival rates at 5years for patients with good, intermediate and high risk cytogenetics were 68%, 47% and 26%,p<0.001. TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk ofprogression: hazard ratio 2.36 (95% CI 1.51-3.70), p<0.001 and 2.15 (1.32-3.48), p=0.002. NRASmutations were associated with an increased risk of progression among standard risk patients withhigh hyperdiploidy: 3.17 (1.15-8.71), p=0.026. Patients classified clinically as standard and high riskhad distinct genetic profiles. The outcome of clinical standard risk patients with high riskcytogenetics was equivalent to clinical high risk patients. Screening patients at relapse for keygenetic abnormalities will enable the integration of genetic and clinical risk factors to improvepatient stratification and outcome.

Publication metadata

Author(s): Irving JAE, Enshaei A, Parker CA, Sutton R, Kuiper RP, Erhorn A, Minto L, Venn NC, Law T, Yu J, Schwab C, Davies R, Matheson E, Davies A, Sonneveld E, den Boer ML, Love SB, Harrison CJ, Hoogerbrugge PM, Revesz T, Saha V, Moorman AV

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2016

Volume: 128

Issue: 7

Pages: 911-922

Print publication date: 18/08/2016

Online publication date: 26/05/2016

Acceptance date: 19/05/2016

Date deposited: 16/06/2016

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology

URL: http://dx.doi.org/10.1182/blood-2016-03-704973

DOI: 10.1182/blood-2016-03-704973

Notes: Irving and Enshaei contributed equally to this study.

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