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Type: Journal article
Title: Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia
Author: Irving, J.
Enshaei, A.
Parker, C.
Sutton, R.
Kuiper, R.
Erhorn, A.
Minto, L.
Venn, N.
Law, T.
Yu, J.
Schwab, C.
Davies, R.
Matheson, E.
Davies, A.
Sonneveld, E.
Den Boer, M.
Love, S.
Harrison, C.
Hoogerbrugge, P.
Revesz, T.
et al.
Citation: Blood, 2016; 128(7):911-922
Publisher: The American Society of Hematology
Issue Date: 2016
ISSN: 0006-4971
Statement of
Julie A. E. Irving, Amir Enshaei, Catriona A. Parker, Rosemary Sutton, Roland P. Kuiper, Amy Erhorn, Lynne Minto, Nicola C. Venn, Tamara Law, Jiangyan Yu, Claire Schwab, Rosanna Davies, Elizabeth Matheson, Alysia Davies, Edwin Sonneveld, Monique L. den Boer, Sharon B. Love, Christine J. Harrison, Peter M. Hoogerbrugge, Tamas Revesz, Vaskar Saha and Anthony V. Moorman
Abstract: Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P < .001). TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk of progression: hazard ratio 2.36 (95% confidence interval, 1.51-3.70, P < .001) and 2.15 (1.32-3.48, P = .002). NRAS mutations were associated with an increased risk of progression among standard-risk patients with high hyperdiploidy: 3.17 (1.15-8.71, P = .026). Patients classified clinically as standard and high risk had distinct genetic profiles. The outcome of clinical standard-risk patients with high-risk cytogenetics was equivalent to clinical high-risk patients. Screening patients at relapse for key genetic abnormalities will enable the integration of genetic and clinical risk factors to improve patient stratification and outcome. This study is registered at as #ISCRTN45724312.
Keywords: Humans
Chromosome Aberrations
Genetic Predisposition to Disease
Disease-Free Survival
Cytogenetic Analysis
Risk Factors
Cohort Studies
Child, Preschool
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
DNA Copy Number Variations
Rights: © 2016 by The American Society of Hematology
DOI: 10.1182/blood-2016-03-704973
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