Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/104640
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
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 1528-0020 |
Statement of Responsibility: | 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 www.clinicaltrials.org as #ISCRTN45724312. |
Keywords: | Humans Chromosome Aberrations Genetic Predisposition to Disease Recurrence Prognosis Disease-Free Survival Cytogenetic Analysis Risk Factors Cohort Studies Demography Mutation Adolescent Child Child, Preschool Infant Female Male 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 |
Published version: | http://dx.doi.org/10.1182/blood-2016-03-704973 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.