Survivors Of Childhood Acute Lymphoblastic Leukemia Research Articles

Predictors of low and very low bone mineral density in long-term childhood acute lymphoblastic leukemia survivors: Toward personalized risk prediction.

Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) 10years after diagnosis. We investigated risk factors for low BMD in long-term cALL survivors. We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5years of event-free survival. Median time since diagnosis was 15.1years. Prevalence of low DXA-derived BMD (Z-score ≤-1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and between 3.7% and 5.8% for very low BMD (Z-score ≤-2). Males had a higher prevalence of low BMD than females for all three outcomes (26%-32% vs. 18%-21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment-related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN-BMD site. Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow-up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.

Exercise and QUality diet After Leukemia (EQUAL): A randomized weight loss trial among adult survivors of childhood leukemia in the Childhood Cancer Survivor Study.

Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity. In this phase 3 efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with body mass index (BMI)≥25 kg/m2 were randomized to a remotely-delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy (CRT). The primary endpoint was the difference in weight loss at 24-months in an intent-to-treat analysis. Analyses were performed using linear mixed effects models. Among 358 survivors (59% female, median attained age: 37 years, IQR: 33-43), baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n=181) and 94.9 kg (20.3) for controls (n=177). Adherence to the intervention was poor; 15% of individuals in the intervention completed 24/30 planned coaching calls. Weight at 24-months was available for 274 (77%) participants. After controlling for CRT, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24-months was -0.4 kg (0.8) for intervention and 0.2 kg (0.6) for control participants (p=0.59). A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL. Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence.

Adult survivors’ perceptions of their childhood and the influences of being treated for acute lymphoblastic leukaemia with allogeneic hematopoietic stem cell transplantation as a child: A phenomenographic study

PurposeAdults who had acute lymphoblastic leukaemia (ALL) as children and were treated with allogeneic hematopoietic stem cell transplantation (aHSCT) may have been affected in their lives due to several long-term complications. From a clinical point of view, it is of interest to study how survivors describe their perceptions of their childhood today. The aim was therefore to describe how adults perceived their childhood and the influences of being treated for ALL with aHSCT as a child. MethodSemi-structured telephone interviews were undertaken with 18 adults who had been treated for childhood ALL with aHSCT and were included in a national cohort of childhood ALL survivors, diagnosed between 1985 and 2007 at an age between 0 and 17 years. A phenomenographic analysis was used. ResultsThree categories emerged: Feeling different, Feeling security and Feeling guilty. The informants felt that they had been different from other children but had felt security with the healthcare professionals and in care. They felt guilty because both their siblings' and parents’ lives had been affected, but at the same time many perceived that they and their family members had become closer to one another. ConclusionsThe results emphasised that adults who had been treated for childhood ALL with aHSCT were affected both in negative and positive ways during their childhood. This indicates the importance for early psychosocial care interventions directed to children during their treatment, but also the need for person-centred psychological care in long-term outpatient clinics.

Neuropsychological task outcomes among survivors of childhood acute lymphoblastic leukemia in Malaysia

This study intended to explore the neuropsychological ramifications in childhood acute lymphoblastic leukemia (ALL) survivors in Malaysia and to examine treatment-related sequelae. A case-control study was conducted over a 2-year period. Seventy-one survivors of childhood ALL who had completed treatment for a minimum of 1 year and were in remission, and 71 healthy volunteers were enlisted. To assess alertness (processing speed) and essential executive functioning skills such as working memory capacity, inhibition, cognitive flexibility, and sustained attention, seven measures from the Amsterdam Neuropsychological Tasks (ANT) program were chosen. Main outcome measures were speed, stability and accuracy of responses. Mean age at diagnosis was 4.50 years (SD ± 2.40) while mean age at study entry was 12.18 years (SD ± 3.14). Survivors of childhood ALL underperformed on 6 out of 7 ANT tasks, indicating poorer sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Duration of treatment, age at diagnosis, gender, and cumulative doses of chemotherapy were not found to correlate with any of the neuropsychological outcome measures. Childhood ALL survivors in our center demonstrated significantly poorer neuropsychological status compared to healthy controls.

Neurocognitive outcome and associated factors in long-term, adult survivors of childhood acute lymphoblastic leukemia, treated without cranial radiation therapy.

There is limited research on neurocognitive outcome and associated risk factors in long-term, adult survivors of childhood acute lymphoblastic leukemia (ALL), without treatment of cranial radiation therapy. Moreover, the impact of fatigue severity and pain interference on neurocognition has received little attention. In this cross-sectional study, we examined neurocognitive outcome and associated factors in this population. Intellectual abilities, verbal learning/memory, processing speed, attention, and executive functions were compared to normative means/medians with one sample t tests or Wilcoxon signed-rank tests. Associations with risk factors, fatigue severity, and pain interference were analyzed with linear regressions. Long-term, adult survivors of childhood ALL (N = 53, 51% females, mean age = 24.4 years, SD = 4.4, mean = 14.7 years post-diagnosis, SD = 3.4) demonstrated above average intellectual abilities, but performed below average in attention, inhibition, processing speed, and shifting (p < 0.001). Executive functioning complaints were significantly higher than normative means, and positively associated with fatigue (p < 0.001). There was no interaction between sex and fatigue and no neurocognitive impairments were associated with pain interference, risk group, age at diagnosis, or sex. Long-term, adult survivors of ALL treated without cranial radiation therapy, demonstrate domain-specific performance-based neurocognitive impairments. However, continued research on the neurocognitive outcome in this population as they age will be important in the coming years. Executive functioning complaints were frequently in the clinical range, and often accompanied by fatigue. This suggests a need for cognitive rehabilitation programs.

QTc intervals at rest and during exercise assessed by group correction formulas in survivors of childhood acute lymphoblastic leukemia

IntroductionEarly signs of subclinical cardiac damage must be identified before they turn into clinical manifestations. Tailoring a formula is relevant for precise QTc evaluation in childhood acute lymphoblastic leukemia (ALL) survivors considering they are at risk of long-term cardiac problems. Therefore, we aim to develop group heart rate correction formulas for QT intervals in childhood ALL survivors at rest and during exercise, and to assess the applicability of these methods across a variety of risk groups exposed to diverse chemotherapy dosages. MethodsTwo hundred and fifty childhood ALL survivors in the PETALE study were classified into 3 groups depending on their prognostic risk group. ECG measurements (QT and RR intervals) were made at rest and during a cardiopulmonary exercise test. QT correction for heart rate was applied using 5 different formulas, which included 2 previously published formulas and 3 group-specific formulas for each sex. ResultsThe QT/RR relation showed 2 different curves between rest and during exercise, which was worse for females. Group-specific QTc formulas allowed adequate heart rate-corrected QT interval, independently of the cumulative dose of doxorubicin received during treatment. Group-specific formulas showed significantly shorter QTc intervals than QTc from Bazett's formula. QTc (Bazett's formula) values surpassed the established clinical norm in 22 males (11%) and 22 females (11%), with a majority occurring during exercise, affecting 15 males (7.5%) and 10 females (5%). ConclusionThis study shows the applicability of personalized group correction of QT/RR data in childhood ALL survivors. Our comprehensive assessments (spanning rest, exercise, and recovery) is an effective approach for risk stratification of cardiac complications in childhood ALL survivors.

Movement efficiency in survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude lifetime cohort study.

Movement efficiency, a measure of neuromuscular biomechanics, may be modified by physical activity. We aimed to assess the risk of and risk factors for low movement efficiency in survivors of childhood acute lymphoblastic leukemia (ALL). Participants underwent an assessment of activity energy expenditure (AEE) with actigraphy, and the gold standard doubly labeled water, where the differences between elimination rates of oxygen and hydrogen from body water are evaluated over a week. Movement efficiency was assessed using the raw residuals of a linear regression between AEEs from accelerometers and doubly labeled water. Elastic-net logistic regressions were used to identify demographic, treatment, and functional variables associated with movement efficiency. The study cohort included 256 non-cancer controls and 302 ALL survivors (48% female), categorized as efficient (N = 24), normal (N = 245), or inefficient (N = 33) based on their movement efficiency. There was no difference in the odds for poor movement efficiency between survivors (n = 33, 10.9%) compared to controls (n = 23, 9.0%, odds ratio [OR]: 1.19, 95% confidence interval [CI]: 0.67, 2.10; p = 0.55). In survivors, neuropathy was associated with a higher risk of being inefficient compared to efficient (OR 4.30, 95% CI 1.03-17.96), while obesity (≥ 30kg/m2) had a protective association (OR 0.18, 95% CI 0.04-0.87). Neuropathy was associated with a higher risk of poor movement efficiency in survivors of childhood ALL. These results further highlight impairments associated with treatment-induced neuropathy in survivors of childhood ALL.

Long-term neurotoxicity among childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC Children Leukemia Group studies

Survival after childhood acute lymphoblastic leukemia (ALL) has increased over the last 40 years with an overall survival above 90%. Survivors may experience neurological late effects secondary to chemotherapy and radiotherapy. This observational retrospective study evaluated the cumulative incidence of neurological late effects among 890 childhood ALL survivors treated in EORTC CLG trials (58741, 58831/2 and 58881) between 1971 and 1998. Median follow-up was 19 years and interquartile range of the follow-up was 15–22 years. At 20 years from the end of treatment, approximately 66% of patients from the 58741 trial (accrual time: 1971–1978) and approximately 15% from the more recent trials had cognitive disturbance grade 1 or higher. Cumulative incidences at 20 years from treatment end of seizures, stroke and leukoencephalopathy were respectively 45%, 16% and 62% in study 58741, 13%, 2% and 5% in study 58831/2, and 8%, 2% and 3% in study 58881. Patients who were 10–17 years of age at diagnosis had a higher incidence of stroke and leukoencephalopathy as compared to those less than 6 years of age. Noteworthy, all neurological late effects continued to occur beyond 5 years after end of treatment. This retrospective study highlights the frequency of neurological late effects in survivors of childhood ALL. With the increase of the overall survival of ALL patients, the role and potential benefit of longitudinal neurological screening should be evaluated in further studies as these neurological late effects become an important public health challenge. This study is part of the larger EORTC CLG 58 Late Adverse Effects (LAE) study (ClinicalTrials.gov Identifier NCT01298388, date of registration February 16, 2011).

Genetic susceptibility and late bone outcomes in childhood acute lymphoblastic leukemia survivors.

Childhood acute lymphoblastic leukemia (cALL) survivors are at increased risk for bone comorbidities, but accurate screening tools for such comorbidities are limited. Polygenic scores (PGS) could stratify cALL survivors for risk of long-term adverse bone outcomes. We evaluated 214 (51% female) cALL survivors from the Prévenir les Effets TArdifs de la LEucémie study (median age 21yr). Bone mineral density (BMD) measurements were obtained using dual X-ray absorptiometry at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and vertebral fractures (VF) were documented using the vertebral deformity criterion. We computed a PGS for adult heel quantitative ultrasound speed of sound (gSOS), known to be associated with the risk of osteoporotic fracture, using imputed genotype data of the participants, and tested it for association with BMD Z-scores and VF risk, adjusting for clinical risk factors, and in sex and prognostic risk-stratified analyses. We found that a gSOS below the mean was associated with lower BMD in all three sites in univariate and multivariate models. In univariate analyses, 1 SD increase in gSOS conferred a 0.16 SD increase in LS-BMD (95% CI 0.005-0.31), whereas a gSOS above the mean was associated with a 0.31 SD higher LS-BMD (95% CI 0.008-0.61), a 0.36 SD higher TB-BMD (95% CI 0.06-0.67), and a 0.43 SD higher FN-BMD (95% CI 0.13-0.72). Models combining gSOS with clinical risk factors explained up to 16% of the variance of BMD phenotypes and obtained an area under the receiver operating characteristic curve for VF of 0.77 in subgroup analyses. Cranial radiation, high cumulative glucocorticoid doses, high risk group, and male sex were significant risk factors for lower BMD Z-scores. In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment-related bone morbidity.

Serum Adipokines as Biomarkers for Surveillance of Metabolic Syndrome in Childhood Acute Lymphoblastic Leukemia Survivors in Low Middle-Income Countries

Background Serum adipokines (leptin and adiponectin) are dysregulated before the onset of metabolic syndrome and hence may be useful biomarkers for screening of cardiometabolic late effects in childhood Acute Lymphoblastic Leukemia (cALL) survivors. Methods We compared serum adipokine levels between 40 cALL survivors (aged 10–18 years, >2 years from treatment completion) with similar controls. A multivariable logistic regression analysis was then done to assess the association of metabolic syndrome in cALL survivors with variables including adipokines and other metabolic parameters, demographic and treatment details, and Dual-energy X-ray absorptiometry scan-derived variables. Results Compared to controls, cALL survivors had a higher prevalence of metabolic syndrome (8/40 vs. 2/40, P = .044) and central obesity (11/40 vs. 4/40, P = 0.042). Median Serum Leptin (7.39 vs. 4.23 ng/ml, P = 0.207) levels and derived Leptin-Adiponectin Ratio (1.44 vs. 0.80, P = 0.598), were higher but not statistically different in our survivors compared to controls; Adiponectin levels were similar (6.07 vs. 5.01 µg/ml, P = 0.283). In the cALL survivors, overweight/obesity (odds ratio [OR] 21.9, P = 0.020) or higher Leptin levels (OR 1.11, P = 0.047), were independently associated with metabolic syndrome. Conclusions Serum Leptin, independently predictive of metabolic syndrome in our cALL survivors, may be tested in larger studies to assess its utility in surveillance and initiation of early preventive measures.

Echocardiographic Parameters Associated With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

Children's exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measured by echocardiography. Participants were 216n childhood acute lymphoblastic leukemia survivors who underwent a maximal cardiopulmonary exercise test and self-reported their daily minutes of moderate to vigorous physical activity. They underwent a complete transthoracic echocardiographic assessment. Systolic and diastolic function analysis and strain images analysis were performed. The associations were studied through the preventive fraction (examined with univariate crude and adjusted logistic regression models) of regular physical activity (≥150min·wk-1) and adequate cardiorespiratory fitness levels (above the median ≥ 32.0mL·kg-1·min-1) on cardiac parameters. Crude analysis shows that regular physical activity was associated with a significant preventive fraction in mitral E/A ratio (56%; P = .013), while adjusted analyses highlighted a nonsignificant reduction of 74% to 37% in the prevalence of cardiac parameters associated with physical activity. Similar associations of adequate cardiorespiratory fitness on cardiac parameters were observed. Adjusted analyses revealed a nonsignificant reduction of 7% to 86% in the prevalence of cardiac parameters associated with cardiorespiratory fitness. This study reports that regular physical activity and adequate cardiorespiratory fitness were associated with a higher preventive fraction. Thus, engaging in physical activity prevents childhood acute lymphoblastic leukemia survivors' cardiac dysfunctions. These findings are novel and clinically relevant in pediatric cardiooncology and provide additional evidence to strengthen the benefits of exercise as long-term care in childhood cancer survivors.

Rate of Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia Treated with Daunorubicin Using Echocardiography and Troponin I

Background and Aim: Acute lymphoblastic leukemia (ALL) is the commonest malignancy in childhood. Childhood ALL Survivors have a lifelong increased risk for cardiovascular morbidity and mortality compared to the general population, mainly caused by chemotherapy with daunorubicin. The aim of the study is to detect the rate of daunorubicin induced cardiotoxicity in children with acute lymphoblastic leukemia during induction phase chemotherapy. Meterials &amp; Methods : This prospective observational study was conducted in the department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU) on 40 newly diagnosed patients of ALL aged between 1 to17.9 years who got daunorubicin during induction. Complete blood count and echocardiography were done and troponin I was measured in all patients before and after completion of induction period. Result: Of the 40 patients, 8 patients (20%) had developed cardiotoxicity evidenced by reduction of left ventricular ejection fraction (LVEF) in echocardiography. Baseline LVEF was 68.80±5.98% which was then reduced to 65.32±7.07% after induction phase of chemotherapy (p=0.023). No significant alteration of troponin I was seen (P= 0.581) between baseline and after completion of induction. Total WBC count and hemoglobin had a significant difference (P&lt;0.05) between baseline and after induction period. Male patients had a greater risk of developing cardiotoxicity than females but statistically was not significant (P=0.643). There was no significant association between age of the patients and cardiotoxicity (P=0.112).Cardiotoxicity was seen higher in patient with initial high WBC count (p=0.039). Echocardiography also reveled increased tendency of mitral regurgitation and left ventricular hypertrophy after induction phase chemotherapy. Conclusion: This study showed the rate of cardiotoxicity was 20% in ALL patients treated with daunorubicin. It also found that LVEF was decreased during therapy.Echocardiography can be used to detect early cardiotoxicity induced by daunorubicin. University Heart Journal 2023; 19(1): 20-25

Diastolic function assessment with left atrial strain in long-term survivors of childhood acute lymphoblastic leukemia

Abstract Background Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to cardiotoxic treatment exposure. Although diastolic function assessment is challenging in this relatively young population, left atrial strain might provide a novel insight into this evaluation. Purpose To examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia survivors using left atrial strain and conventional echocardiographic parameters. Methods Long-term survivors who were diagnosed at a single center between 1985-2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and strain were compared, the latter measured during the three atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups. Results 90 survivors (24.6±9.7 years, time since diagnosis 18 [11-26] years) and 58 controls were analyzed. PALS and LACS were significantly reduced compared to the control group: 46.4±11.2 vs 52.1±11.7 (p=0.003) and 32.5±8.8 vs 38.2±9.3 (p=0.003), respectively (figure 1B). Conventional diastolic parameters and PACS were similar between the groups (figure 1A). The reductions in PALS and LACS were associated to cardiotoxic treatment exposure in age and sex adjusted analysis (≥ moderate risk, low risk, controls): 45.4±10.5, 49.5±12.9, 52.1±11.7 (padj=0.003) and 31.7±9.0, 35.2±7.5, 38.2±9.3 (padj=0.001), respectively (figure 2). Conclusions Long-term childhood leukemia survivors showed a subtle impairment in diastolic function that was detected using atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher cardiotoxic treatment exposure.Figure 1Figure 2

Trends in physical functioning in acute lymphoblastic leukemia and non-Hodgkin lymphoma survivors across three decades.

The impact of changes in therapy for childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on the prevalence of physical performance limitations and participation restrictions among survivors is unknown. We aimed to describe the prevalence of reduced function among ALL and NHL survivors by treatment era. Participants included survivors of childhood ALL and NHL, and a cohort of their siblings, participating in the Childhood Cancer Survivor Study (CCSS). Physical function was measured using questionnaire. The prevalence of reduced function was compared to siblings using generalized estimating equations, overall and stratified by treatment decade. Associations between organ system-specific chronic conditions (CTCAE v4.03) and function were also evaluated. Among 6511 survivors (mean age 25.9years (standard deviation 6.5)) and 4127 siblings, risk of performance limitations (15.2% vs. 12.5%, prevalence ratio [PR] = 1.5, 95%CI = 1.3-1.6), restrictions in personal care (2.0% vs. 0.6%, PR = 3.1, 95% CI = 2.0-4.8), routine activities (5.5% vs. 1.6%, PR = 3.6, 95% CI = 2.7-4.8), and work/school attendance (8.8% vs. 2.1%, PR = 4.5, 95% CI = 3.6-5.7) was increased in survivors vs. siblings. The prevalence of survivors reporting reduced function did not decrease between the 1970s and 1990s. The presence of neurological and cardiovascular conditions was associated with reduced function regardless of treatment decade. Despite changes in therapy, the prevalence of poor physical function remained constant between the 1970s and 1990s. The CCSS clinical trial registration number is NCT01120353 (registered May 6, 2010). Our findings support screening for reduced physical function so that early interventions to improve physicalperformance and mitigate chronic disease can be initiated.

3 Clinical Utility of Neurocognitive Monitoring During Therapy in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)

Objective:Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.Participants and Methods:Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.Results:During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.Conclusions:Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.

24 Adaptive Functioning and Academic Achievement in Survivors of Childhood Acute Lymphoblastic Leukemia

Objective:Executive functioning (EF) and socioeconomic status (SES) are associated with functional outcomes (adaptive functioning and academic achievement) in healthy controls and pediatric populations with executive dysfunction. However, these relationships have yet to be investigated in survivors of childhood acute lymphoblastic leukemia (ALL), a population with EF impairment resulting from disease and treatment characteristics. The objective of this study was to examine the associations of functional outcomes with EF and SES (neighborhood-specific variables and academic support) in survivors of childhood ALL.Participants and Methods:Forty-four participants (38.6% female, 72.7% non-Hispanic White, ages 6-17) previously diagnosed with low-risk or standard-risk pre-B cell ALL and treated with chemotherapy-only were included. Participants were evaluated on performance-based measures of EF (cognitive flexibility, verbal fluency, working memory, and processing speed) and academic achievement (word reading and math calculation), and parent-ratings of EF and adaptive functioning. All measures were expressed as T-scores with lower scores indicating better performance. Neighborhood-specific variables were based on participants’ zip codes and census block group, and included area deprivation index (ADI) and child opportunity index (COI). Lower ADI and COI indicate lesser deprivation and greater opportunity. Individualized education plan (IEP) status was used as a proxy of academic support, coded dichotomously as with or without IEP. Percentages of participants showing impairments in functional outcomes were calculated using a cutoff of &gt; 1 SD above the normative mean. Partial correlations were conducted while controlling for age at evaluation, age at diagnosis, sex, and verbal IQ, to examine whether participants with poorer performance-based and parent-rated EF would show reduced functional outcomes. Multiple regression analyses were conducted to evaluate whether neighborhood-specific variables and IEP status would predict functional outcomes while controlling for covariates.Results:Compared to population norms, survivors of childhood ALL showed worse functional outcomes. Within adaptive functioning, 45.5% of participants showed impairment in activities of daily living and leadership. Adaptive functioning was significantly positively correlated with parent-rated, but not performance-based, EF (r=0.694, p&lt;0.001). Compared to female survivors, male survivors were at increased risk for adaptive functioning difficulties (r=-0.401, p&lt;0.05). Impairments for word reading and math calculation were 25% and 41.7%, respectively. Greater math calculation was associated with better verbal fluency (r=0.378, p&lt;0.05) and processing speed (r=0.439, p&lt;0.05). Older participants at evaluation (/3=-0.580, p&lt;0.001) and those without IEP support (ß=0.465, p&lt;0.05) showed better word reading. Lower ADI predicted better verbal fluency (ß=0.282, p=0.041), however, neighborhood-specific variables were not associated with functional outcomes.Conclusions:Prior findings indicate that performance-based measures and parent-ratings assess different constructs of EF. Thus, adaptive functioning may relate more to the behavioral construct of EF than its cognitive construct. Current findings also suggest that male survivors are at increased risk for reduced adaptive functioning, consistent with recent reports that male survivors of ALL are at greater risk for specific neurocognitive outcomes. Overall, functional outcomes may be more strongly related to EF than neighborhood-specific variables. Long-term goals include early screening of adaptive and academic difficulties, targeted intervention, and neuropsychological monitoring to support pediatric survivors’ neurocognitive and psychosocial development.

Weight status in survivors of childhood acute lymphocytic leukemia in South Korea: a retrospective descriptive study.

This study investigated weight status in survivors of childhood acute lymphocytic leukemia (ALL) and identified related factors. A retrospective review of the electronic medical records of survivors of childhood ALL (n=230) was conducted. We analyzed the survivors' characteristics, including sex, age, weight status at diagnosis, central nervous system involvement, risk classification, length of treatment, radiation therapy, and hematopoietic stem cell transplantation. Analysis of variance and the chi-squared test were applied to investigate influencing factors. The weight status distribution was as follows: 23 individuals (10.0%) were classified as underweight, 151 individuals (65.7%) were healthy weight, and 56 individuals (24.3%) were overweight/obese. Age at diagnosis (F=10.03, p<.001), weight status at diagnosis (x2=43.41, p<.001), and risk classification (F=10.98, p=0.027) showed significant differences among the weight status groups. Survivors who were older at diagnosis and those in the very high-risk category had a higher likelihood of experiencing underweight status during their survivorship, while survivors who were overweight/obese at diagnosis were more likely to remain overweight/obese at the time of survival. Considering the potential health implications related to an unhealthy weight status in survivors of ALL, it is imperative to undertake early identification and implement interventions for at-risk individuals.

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

Relationship between cardiac mechanical properties and cardiac magnetic resonance imaging at rest in childhood acute lymphoblastic leukemia survivors.

The characterization of cardiac mechanical properties may contribute to better understanding of doxorubicin-induced cardiotoxicity. Our study aims to investigate the relationship between cardiac mechanical properties, T1 and T2 relaxation times and partition coefficient.Fifty childhood acute lymphoblastic leukemia survivors underwent a cardiac magnetic resonance (CMR) at rest on a 3T MRI system and included a standard ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Partition coefficient, ejection fraction, end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated. CircAdapt model was used to study cardiac mechanical performance (left ventricle stiffness (LVS), contractility (LVC) and pressure (Pmin and Pmax), cardiac work efficiency (CWE) and ventricular arterial coupling).In the whole cohort, our results showed that LVC (R2 = 69.2%, r = 0.83), Pmin (R2 = 62.9%, r = 0.79) and Pmax can be predicted by significant CMR parameters, while T1 (R2 = 23.2%, r = 0.48) and partition coefficient (R2 = 13.8%, r = 0.37) can be predicted by significant cardiac mechanical properties. In SR group LVS (R2 = 94.8%, r = 0.97), LVC (R2 = 93.7%, r = 0.96) and Pmin (R2 = 90.6%, r = 0.95) can be predicted by significant cardiac mechanical properties, while in HR + DEX group CWE (R2 = 49.8%, r = 0.70) can be predicted by significant cardiac mechanical properties. Partition coefficient (R2 = 72.6%, r = 0.85) can be predicted by significant CMR parameters in SR group.Early characterization of cardiac mechanical properties from CMR parameters has the potential to early detect doxorubicin-induced cardiotoxicity.

Regular Physical Activity To Improve Cardiac Abnormalities Measured By Echocardiography In Childhood Acute Lymphoblastic Leukemia Survivors

Regular Physical Activity To Improve Cardiac Abnormalities Measured By Echocardiography In Childhood Acute Lymphoblastic Leukemia Survivors