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PURPOSE: Early identification of childhood cancer survivors at high risk for treatment-related cardiomyopathy may improve outcomes by enabling intervention before development of heart failure. We implemented artificial intelligence (AI) methods using the Children's Oncology Group guideline–recommended baseline ECG to predict cardiomyopathy. MATERIAL AND METHODS: Seven AI and signal processing methods were applied to 10-second 12-lead ECGs obtained on 1,217 adult survivors of childhood cancer prospectively followed in the St Jude Lifetime Cohort (SJLIFE) study. Clinical and echocardiographic assessment of cardiac function was performed at initial and follow-up SJLIFE visits. Cardiomyopathy was defined as an ejection fraction < 50% or an absolute drop from baseline ≥ 10%. Genetic algorithm was used for feature selection, and extreme gradient boosting was applied to predict cardiomyopathy during the follow-up period. Model performance was evaluated by five-fold stratified cross-validation. RESULTS: The median age at baseline SJLIFE evaluation was 31.7 years (range 18.4-66.4), and the time between baseline and follow-up evaluations was 5.2 years (0.5-9.5). Two thirds (67.1%) of patients were exposed to chest radiation, and 76.6% to anthracycline chemotherapy. One hundred seventeen (9.6%) patients developed cardiomyopathy during follow-up. In the model based solely on ECG features, the cross-validation area under the curve (AUC) was 0.87 (95% CI, 0.83 to 0.90), whereas the model based on clinical features had an AUC of 0.69 (95% CI, 0.64 to 0.74). In the model based on ECG and clinical features, the cross-validation AUC was 0.89 (95% CI, 0.86 to 0.91), with a sensitivity of 78% and a specificity of 81%. CONCLUSION: AI using ECG data may assist in the identification of childhood cancer survivors at increased risk for developing future cardiomyopathy. [ABSTRACT FROM AUTHOR]

Purpose: Frailty, a phenotype reported among 9.9% of individuals 65 years old and older (9.6% of women; 5.2% of men), has not been assessed among adult childhood cancer survivors (CCS). We estimated the prevalence of frailty and examined associations with morbidity and mortality., Methods: Participants included 1,922 CCS at least 10 years from original cancer diagnosis (men, 50.3%; mean age, 33.6 ± 8.1 years) and a comparison population of 341 participants without cancer histories. Prefrailty and frailty were defined as two and ≥ three of the following conditions: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Morbidity was defined as grade 3 to 4 chronic conditions (Common Terminology Criteria for Adverse Events version 4.0). Fisher's exact tests were used to compare, by frailty status, percentages of those with morbidity. In a subset of 162 CCS who returned for a second visit, Poisson regression was used to evaluate associations between frailty and new onset morbidity. Cox proportional hazards regression was used to evaluate associations between frailty and death., Results: The prevalence of prefrailty and frailty were 31.5% and 13.1% among women and 12.9% and 2.7% among men, respectively, with prevalence increasing with age. Frail CCS were more likely than nonfrail survivors to have a chronic condition (82.1% v 73.8%). In models adjusted for existing chronic conditions, baseline frailty was associated with risk of death (hazard ratio, 2.6; 95% CI, 1.2 to 6.2) and chronic condition onset (relative risk, 2.2; 95% CI, 1.2 to 4.2)., Conclusion: The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.

Purpose: To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic cells., Patients and Methods: Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and 2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm B). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV)., Results: Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P =.045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P =.63). The incidence of toxicity did not differ significantly between the two treatment arms (P =.53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P =.58)., Conclusion: Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.

Purpose: To determine the impact of MLL rearrangements on the outcome of children with acute myeloid leukemia (AML)., Patients and Methods: We analyzed the clinical and biologic features of 298 infants and children with primary AML treated on four consecutive institutional clinical trials. The Kaplan-Meier method was used in survival analysis and the Cox proportional-hazards model was used to analyze the effect of potential prognostic factors on event-free survival (+/- 1 SE)., Results: Molecular studies of 152 cases detected 42 with MLL rearrangements. The karyotypes of these 42 revealed the t(9;11) (15 cases), abnormalities of chromosomes 10 and 11 (nine cases), the t(11;19) (four cases), other abnormalities of 11q23 (seven cases), and miscellaneous rearrangements (seven cases). Among these 42 patients, the 15 whose leukemic cells carried the t(9;11) had a better outcome (66% +/- 15%) than the other 27 (25.9% +/- 11.2%; P =.004). Cases with the t(9;11) were also characterized by M5 AML morphology (21 of 23 cases). Of the 63 patients with M5 AML, the 21 whose leukemic cells demonstrated the t(9;11) had a better outcome (71.1% +/- 11%) than the other 42 (25.8% +/- 7.9%; P =.0004). The only independent factors indicating a favorable prognosis were presenting leukocyte count less than 50 x 10(9)/L (relative risk of relapse, 0.73; 95% confidence interval, 0.55 to 0.97; P =.03) and the t(9;11) (relative risk of relapse, 0.32; 95% confidence interval, 0.16 to 0.64; P =.002)., Conclusion: We conclude that the t(9;11) is the most favorable genetic factor for patients with AML treated at our institution.