Dataset Information

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

ABSTRACT: DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728.

SUBMITTER: Ghazavi F

PROVIDER: S-EPMC4591763 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

Ghazavi Farzaneh F Clappier Emmanuelle E Lammens Tim T Suciu Stefan S Caye Aurélie A Zegrari Samira S Bakkus Marleen M Grardel Nathalie N Benoit Yves Y Bertrand Yves Y Minckes Odile O Costa Vitor V Ferster Alina A Mazingue Françoise F Plat Geneviève G Plouvier Emmanuel E Poirée Marilyne M Uyttebroeck Anne A van der Werff-Ten Bosch Jutte J Yakouben Karima K Helsmoortel Hetty H Meul Magali M Van Roy Nadine N Philippé Jan J Speleman Frank F Cavé Hélène H Van Vlierberghe Pieter P De Moerloose Barbara B

Haematologica 20150702 10

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases ...[more]

PMID: 26137961

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Project description:due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive. We investigated potential risk factors for decreased daily life quality and life challenges in long-term childhood ALL survivors enrolled between 1971 and 1998 in EORTC studies. self-report questionnaires were collected from 186 survivors (109 females; mean age at diagnosis 5.62 years, range 0.2-14.7; median time since diagnosis of 20.5 years (12.9-41.6)), including the Short-Form Health Survey (SF-12) and Impact of Cancer-Childhood Survivors (IOC-CS). Multivariable linear regression models were used to assess the impact of gender, age at diagnosis, relapse/second neoplasm, National Cancer Institute (NCI) risk group and cranial radiotherapy on 2 subscales of the SF-12 (physical and mental health) and five subscales of the IOC-CS (life challenges, body and health, personal growth, thinking and memory problems and socializing). mental component scores of SF-12 were not significantly associated with any risk factor. Physical component scores were lower in relapsed, irradiated and NCI high-risk patients. Regarding IOC-CS negative impact subscales, life challenges was more negatively impacted by cancer in female, younger (i.e., <6 years) and relapsed patients. Regarding the positive impact scales, personal growth was more positively impacted in relapsed patients, whereas body and health, and socializing, were less positively impacted in these patients, compared to non-relapsed patients. Socializing was more positively impacted in older patients (>6 years). this study demonstrates that long-term outcomes can be both adverse and positive, depending on the patient's demographic and clinical characteristics. Younger, female, and relapsed patients might encounter more life challenges years after their disease, while physical challenges could occur more often in relapsed and high-risk patients. Finally, the positive effect on socializing in the older patients sheds new light on the importance of peer interactions for this subgroup. Specific individual challenges thus need specialized support for specific subgroups.

Dataset Information

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

Publications

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

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