Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia.
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 is less well understood and has not been studied comprehensively. We analysed cytogenetic data from 427 childr...
| Hoofdauteurs: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
American Society of Hematology
2016
|
| _version_ | 1826306907450638336 |
|---|---|
| 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 Boer, M Love, S Harrison, C Hoogerbrugge, P Revesz, T Saha, V Moorman, A |
| author_facet | 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 Boer, M Love, S Harrison, C Hoogerbrugge, P Revesz, T Saha, V Moorman, A |
| author_sort | Irving, J |
| collection | OXFORD |
| description | 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 is less well understood and has not been studied comprehensively. We analysed 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 (CNA) and mutations. Cytogenetic risk groups were predictive of outcome post-relapse and survival rates at 5 years 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 of progression: hazard ratio 2.36 (95% CI 1.51-3.70), p<0.001 and 2.15 (1.32-3.48), p=0.002. NRAS mutations were associated with an increased risk of progression among standard risk patients with high hyperdiploidy: 3.17 (1.15-8.71), p=0.026. 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. Clinicaltrials.org: ISCRTN45724312. |
| first_indexed | 2024-03-07T06:55:02Z |
| format | Journal article |
| id | oxford-uuid:fdd675bf-31fa-4100-a26e-81a2e922d519 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:55:02Z |
| publishDate | 2016 |
| publisher | American Society of Hematology |
| record_format | dspace |
| spelling | oxford-uuid:fdd675bf-31fa-4100-a26e-81a2e922d5192022-03-27T13:31:52ZIntegration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fdd675bf-31fa-4100-a26e-81a2e922d519EnglishSymplectic Elements at OxfordAmerican Society of Hematology2016Irving, JEnshaei, AParker, CSutton, RKuiper, RErhorn, AMinto, LVenn, NLaw, TYu, JSchwab, CDavies, RMatheson, EDavies, ASonneveld, EBoer, MLove, SHarrison, CHoogerbrugge, PRevesz, TSaha, VMoorman, ASomatic 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 is less well understood and has not been studied comprehensively. We analysed 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 (CNA) and mutations. Cytogenetic risk groups were predictive of outcome post-relapse and survival rates at 5 years 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 of progression: hazard ratio 2.36 (95% CI 1.51-3.70), p<0.001 and 2.15 (1.32-3.48), p=0.002. NRAS mutations were associated with an increased risk of progression among standard risk patients with high hyperdiploidy: 3.17 (1.15-8.71), p=0.026. 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. Clinicaltrials.org: ISCRTN45724312. |
| spellingShingle | 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 Boer, M Love, S Harrison, C Hoogerbrugge, P Revesz, T Saha, V Moorman, A Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia. |
| title | Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia. |
| title_full | Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia. |
| title_fullStr | Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia. |
| title_full_unstemmed | Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia. |
| title_short | Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukaemia. |
| title_sort | integration of genetic and clinical risk factors improves prognostication in relapsed childhood b cell precursor acute lymphoblastic leukaemia |
| work_keys_str_mv | AT irvingj integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT enshaeia integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT parkerc integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT suttonr integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT kuiperr integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT erhorna integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT mintol integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT vennn integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT lawt integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT yuj integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT schwabc integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT daviesr integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT mathesone integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT daviesa integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT sonnevelde integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT boerm integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT loves integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT harrisonc integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT hoogerbruggep integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT reveszt integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT sahav integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia AT moormana integrationofgeneticandclinicalriskfactorsimprovesprognosticationinrelapsedchildhoodbcellprecursoracutelymphoblasticleukaemia |