Dataset Information

Automated Global Longitudinal Strain Assessment in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.

ABSTRACT: There is limited evidence that supports the use of the global longitudinal strain (GLS) in long-term cardiac monitoring of childhood acute lymphoblastic leukemia survivors (CLSs). Our aim was to assess the utility of automated GLS to detect left ventricular systolic dysfunction (LVSD) in long-term CLSs. Asymptomatic and subclinical LVSD were defined as LVEF < 50% and GLS < 18.5%, respectively. Echocardiographic measurements and biomarkers were compared with a control group. Inverse probability weighting was used to reduce confounding. Regression models were used to identify factors associated with LVEF and GLS in the survivors. Ninety survivors with a median follow-up of 18 (11-26) years were included. The prevalence of LVSD was higher using GLS than with LVEF (26.6% vs. 12.2%). The measurements were both reduced as compared with the controls (p < 0.001). There were no differences in diastolic parameters and NT-ProBNP. Survivors were more likely to have Hs-cTnI levels above the detection limit (40% vs. 17.2%, p = 0.006). The dose of anthracycline was associated with LVEF but not with GLS in the survivors. Biomarkers were not associated with GLS or LVEF. In conclusion, LVSD detection using automated GLS was higher than with LVEF in long-term CLSs. Its incorporation into clinical routine practice may improve the surveillance of these patients.

SUBMITTER: Gonzalez-Manzanares R

PROVIDER: S-EPMC8946759 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Automated Global Longitudinal Strain Assessment in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.

Gonzalez-Manzanares Rafael R Castillo Juan C JC Molina Jose R JR Ruiz-Ortiz Martin M Mesa Dolores D Ojeda Soledad S Anguita Manuel M Pan Manuel M

Cancers 20220315 6

There is limited evidence that supports the use of the global longitudinal strain (GLS) in long-term cardiac monitoring of childhood acute lymphoblastic leukemia survivors (CLSs). Our aim was to assess the utility of automated GLS to detect left ventricular systolic dysfunction (LVSD) in long-term CLSs. Asymptomatic and subclinical LVSD were defined as LVEF < 50% and GLS < 18.5%, respectively. Echocardiographic measurements and biomarkers were compared with a control group. Inverse probability w ...[more]

PMID: 35326663

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Project description:PurposeTo examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol.Patients and methodsThis longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education.ResultsIntelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue.ConclusionSurvivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function.

Project description:PurposeThe purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.MethodsWe evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected. Parent report of behavior and direct cognitive testing of survivors was conducted at end of therapy, and survivors completed neurocognitive testing when > 5 years post-diagnosis.ResultsAt the end of chemotherapy, survivors (52% female; mean age 9.2 years) demonstrated higher frequency of impairment in sustained attention (38%) and parent-reported inattention (20%) compared to population expectations (10%). At long-term follow-up, survivors (mean age 13.7 years; 7.6 years post-diagnosis) demonstrated higher impairment in executive function (flexibility 24%, fluency 21%), sustained attention (15%), and processing speed (15%). Sustained attention improved from end of therapy to long-term follow-up (p < 0.001). Higher methotrexate AUC and greater number of intrathecal injections were associated with attention problems (p = 0.009, p = 0.002, respectively) at the end of chemotherapy and executive function (p < 0.001, p = 0.02, respectively) problems at long-term follow-up. Attention problems at the end of therapy were not associated with executive function problems at long-term follow-up (p's > 0.05). The direct effect of chemotherapy exposure predicted outcomes at both time points.Conclusions and implications for cancer survivorsSurvivors should be monitored for neurocognitive problems well into long-term survivorship, regardless of whether they show attention problems at the end of therapy. Treatment exposures are the best predictor of long-term complications.

Project description:BackgroundIncreasing attention has been dedicated to investigate modifiable risk factors of late effects in survivors of childhood cancer. This study aims to evaluate neurocognitive and behavioral functioning in a relatively young cohort of survivors of childhood acute lymphoblastic leukemia (ALL) in Hong Kong, and to identify clinical and socio-environmental factors associated with these outcomes.MethodsThis analysis included 152 survivors of childhood ALL who were ≥5 years post-diagnosis (52% male, mean [SD] age 23.5[7.2] years at evaluation, 17.2[7.6] years post-diagnosis). Survivors completed performance-based neurocognitive tests, and reported their emotional and behavioral symptoms using the Child/Adult Behavior Checklist. Socio-environmental variables (living space, fatigue, physical activity, family functioning, and academic stress) were self-reported using validated questionnaires. Clinical variables and chronic health conditions were extracted from medical charts. Multivariable linear modeling was conducted to test identify factors associated with neurocognitive/behavioral outcomes, adjusting for current age, sex, age at diagnosis and cranial radiation. An exploratory mediation analysis was performed to examine the mediating effects of risk factors on neurocognitive and behavioral outcomes.ResultsAs compared to population norms, a minority of survivors developed mild-moderate impairment in motor processing speed (36.2%), memory (9.2%) and attention measures (4.0%-10.5%). Survivors also reported attention problems (12.5%), sluggish cognitive tempo (23.7%) and internalizing (depressive, anxiety and somatic symptoms) problems (17.1%). A minority of survivors developed mild-moderate treatment-related chronic conditions (n=37, 24.3%). As compared to survivors without chronic conditions, survivors with chronic conditions had more executive dysfunction (B=5.09, standard error [SE]=2.05; P=0.014) and reported more attention problems (B=5.73, SE=1.43; P<0.0001). Fatigue and poor family functioning was associated with multiple measures of behavior problems (all P<0.001). A lower level of physical activity was correlated with more self-reported symptoms of inattention (B= -1.12, SE=0.38, P=0.004) and sluggish cognitive tempo (B=-1.22, SE=0.41, P=0.003). Exploratory analysis showed that chronic health conditions were associated with behavioral measures through fatigue as the mediator.ConclusionThe majority of young Chinese survivors of ALL had normal cognitive and behavioral function. Regular monitoring of behavioral function should be performed on survivors who develop treatment-related chronic conditions. Health behavior and socio-environment factors may be potentially modifiable risk factors associated with health outcomes in survivors.

Dataset Information

Automated Global Longitudinal Strain Assessment in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.

Publications

Automated Global Longitudinal Strain Assessment in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.

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