Survivors Of Pediatric Acute Lymphoblastic Leukemia Research Articles

Uncovering possible silent acquired long QT syndrome using exercise stress testing in long-term pediatric acute lymphoblastic leukemia survivors.

An example of chemotherapy-induced cardiotoxicity in cancer survivors is acquired long QT syndrome (aLQTS), which may cause serious yet preventable life-threatening consequences. Our objective was to identify and characterize childhood acute lymphoblastic leukemia (ALL) survivors with possible aLQTS using maximal exercise testing. In this cross-sectional study with exploratory analysis, a total of 250 childhood ALL survivors were evaluated for abnormal QT interval prolongation using the McMaster cycle exercise test. A total of 198 survivors (102 males; 96 females), having reached their peak (mean 32.1 ± 8.4 mL/kg/min; range 15.5-57.8 mL/kg/min), were included in our analyses. Two survivors were excluded for possible congenital LQTS. QT intervals were corrected for heart rate using the Bazett, Fridericia, and Rautaharju formulas at rest (supine, sitting, and standing positions), at the end of each stage of the CPET, and at 1, 3, and 5 minutes into the recovery period. The corrected QT (QTc) of borderline (n = 37) and long QT survivors (n = 20) was significantly longer than normal survivors (n = 141) at rest, exercise, and recovery. Out of 57 survivors presenting an abnormal QTc prolongation, 40 survivors (70%) showed no QT interval anomalies at rest but developed various anomalies during exercise. No significant differences were found between the groups for any of the measured clinical characteristics or cardiac parameters. The standardization of exercise testing in the regular follow-up of oncology patients is necessary for appropriate cardiac prevention and surveillance to enhance the health and quality of life of the ever-increasing number of cancer survivors.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Effect of apolipoprotein E (APOE) gene polymorphisms on the lipid profile of children being treated for acute lymphoblastic leukemia

BackgroundMedications used to treat acute lymphoblastic leukemia (ALL), such as l-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes.ProcedureWe aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls.ResultsThe only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence).ConclusionsLipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings.

Dose-Related Effect of Chemotherapy on Bone Mineral Density Among Pediatric Acute Lymphoblastic Leukemia Survivors

OBJECTIVES Reduced bone mineral density (BMD) can negatively affect lifelong skeletal health by ­increasing the risk for developing osteopenia and osteoporosis. This study evaluated the relationship between BMD and cumulative doses of intravenous (IV) methotrexate (MTX) and glucocorticoids in pediatric acute lymphoblastic leukemia (ALL) survivors. The association between BMD and vitamin D concentrations measured at the time of entry into the long-term follow-up program was also assessed. METHODS This retrospective study included pediatric ALL survivors who had received a dual-energy X-ray absorptiometry (DXA) scan after the end of therapy (EOT) or within the 6 months prior to the EOT. Low/­intermediate and high cumulative IV MTX doses were defined as doses less than 20,000 mg/m2 and ­greater than or equal to 20,000 mg/m2, respectively. Descriptive statistics, Student t test, and linear ­regression were used to analyze the data. RESULTS A total of 62 patients, with 34 patients in the low/intermediate and 28 patients in the high ­cumulative IV MTX dose groups, were analyzed. The median time from EOT to DXA scan was 2.3 years. The mean DXA lumbar spine z score was significantly lower in the high cumulative IV MTX dose group ­compared with the low/intermediate dose group (−0.86 vs −0.14; p = 0.008). Cumulative glucocorticoid doses and vitamin D concentrations were not associated with BMD. CONCLUSIONS Pediatric patients who had received cumulative IV MTX doses of greater than or equal to 20,000 mg/m2 during their ALL treatment had lower BMD than those who had received lower cumulative doses.

Effectiveness of a dose-graded aerobic exercise regimen on cardiopulmonary fitness and physical performance in pediatric survivors of acute lymphoblastic leukemia: a randomized clinical trial.

To determine whether a 12-week supervised dose-graded aerobic exercise (D-GAE) training, when implemented in conjunction with traditional rehabilitation, could help pediatric survivors of acute lymphoblastic leukemia (ALL) enhance their cardiopulmonary capacity and improve their physical performance. Fifty-eight pediatric survivors of ALL (age 13.78 ± 2.47years; boys 60.34%) were assigned at random to either undergo the D-GAE in addition to the traditional physical rehabilitation (D-GAE group; n = 29) or the traditional physical rehabilitation solely (control group; n = 29). The cardiopulmonary fitness (peak oxygen uptake (VO2peak), ventilatory equivalent (VEq/VO2), minute ventilation (VE, L/min), oxygen pulse (O2P), maximum heart rate (HRmax), 1-min heart rate recovery (HRR1), and respiratory exchange ratio (RER)) and physical performance (6-min walk test (6-MWT), timed up and down stairs (TUDS), and 4 × 10-m shuttle run test (4 × 10mSRT)) were assessed on the pre- and post-intervention occasions. The mixed-model ANOVA revealed a meaningful increase of VO2peak (P = .002), VE (P = .026), O2P (P = .0009), HRmax (P = .004), and HRR1 (P = .011), and reduction of VEq/VO2 (P = .003) and RER (P = .003) in the D-GAE group compared with the control group. Besides, the analysis detected a favorable increase in the physical performance for the D-GAE group (6-MWT (P = .007), TUDS (P < .001), 4 × 10mSRT (P = .009)). A 12-week D-GAE program in conjunction with traditional rehabilitation holds promise in enhancing cardiopulmonary fitness and improving the physical performance of pediatric survivors of ALL. Clinicians and physical rehabilitation professionals can, therefore, integrate the D-GAE into the traditional rehabilitation protocols for such a patient population to optimize their cardiopulmonary fitness and physical function, while also facilitating a gradual transition to practice and adaption. The favorable outcomes of this study bolster the inclusion of D-GAE as a crucial element in the care and rehabilitation of pediatric survivors of ALL. By embracing these findings, healthcare professionals and oncologists can contribute to mitigating the long-term cardiopulmonary and physical complications associated with cancer treatments and fostering a state of enhanced well-being and increased physical activity among survivors.

SIRT5 Regulates Energy Metabolism and Survival in Acute Lymphoblastic Leukemia Cells

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children, with a second incidence peak in adults over 60 years old. Long-term survival with currently available therapy regimens is &amp;gt;90% in children, but &amp;lt;50% in adults, reflecting differences in disease biology and tolerance of aggressive multi-agent chemotherapy regimens. While CAR-T cell therapy provides effective salvage to patients with relapsed B-cell ALL (B-ALL), outcome in relapsed T-ALL is exceptionally poor. In addition, therapy-related chronic functional impairment in pediatric ALL survivors are common. Less toxic, and more effective therapies are needed to improve ALL survival, particularly in adults, and reduce toxicity and functional impairment in all patients. There is evidence that energy restriction creates a barrier to malignant transformation as B cell precursors undergo somatic hypermutation and during T cell receptor diversification. Mutational inactivation of B-lineage transcription factors such as IKZF1 and PAX5 in B-ALL and aberrant expression of T-lineage regulators such as TLX1/3 in T-ALL disables this metabolic brake, promoting malignant transformation of B and T lymphoid precursors, respectively. Metabolism is being recognized as an attractive target in cancer therapy, but metabolic plasticity often limits the efficacy of targeting single metabolic pathways. SIRT5 is a lysine deacylase that regulates multiple metabolic pathways, including energy metabolism. We have previously reported that a subset of acute myeloid leukemia (AML) cases depends on SIRT5 as a master regulator of central energy metabolism, implicating SIRT5 as a therapy target in AML. We hypothesized that this metabolic vulnerability may extend to ALL. To study the function of SIRT5 in ALL, we stably expressed doxycycline (Dox)-inducible shRNAs targeting SIRT5 in ALL cell lines and primary samples. Knockdown (KD) of SIRT5 significantly inhibited growth and increased apoptosis in B-ALL and T-ALL cell lines. Similar results were seen with primary cells relapsed ALL, whereas SIRT5 KD had no effect on colony formation by normal CD34 + cord blood cells. We also injected mice with Jurkat T-ALL cells expressing Dox-inducible sh SIRT5 and luciferase. Dox-induced SIRT5 KD abrogated disease initiation and eliminated established disease (Figure 1A). To determine whether ALL cells require SIRT5 to maintain a metabolic state that is permissive to malignant transformation, we next evaluated the effect of SIRT5 disruption on energy metabolism, using Seahorse extracellular flux analysis. We found that SIRT5 deficient T-ALL cells had lower rates of both oxidative phosphorylation and glycolysis in comparison to SIRT5 wild type (WT) cells (Figure 1B). Next, to evaluate dependency of SIRT5-KD on multiple genotypes and therapy-resistant ALL, we engineered 30 ALL cell lines to stably express doxycycline sh SIRT5 representing B and T cell origin, diverse genotypes, and including drug resistant lines. We found that several B-ALL and T-ALL cell lines are highly dependent on SIRT5 for growth and survival, while others are not, showing a large range of sensitivity to SIRT5 KD. Therefore, to elucidate the potential mechanisms underlying SIRT5 dependence in ALL, we first analyzed whether SIRT5 KD differentially affects OXPHOS and glycolysis. Preliminary analysis of mitochondrial respiration upon SIRT5 KD suggested that OXPHOS and glycolysis are reduced in SIRT5-dependent cells, but not in SIRT5-independent cells upon SIRT5 KD. Finally, to determine whether Sirt5 disruption affects energy metabolism in normal hematopoietic stem cells (HSCs), we generated a tamoxifen-inducible conditional hematopoietic cell-specific Sirt5 knockout (KO) model. In preliminary experiments, we found no difference in mitochondrial respiration between normal HSCs with or without genetic absence of Sirt5, suggesting that leukemic cells, but not normal hematopoietic stem cells are dependent on Sirt5 for regulation of energy metabolism. Collectively, our results suggest that SIRT5 plays a critical oncogenic role in the development and maintenance of a subset of ALL, providing a rationale for the development of a clinical SIRT5 inhibitor. Targeting master regulators rather than single pathways may circumvent plasticity-based resistance in ALL.

19 Processing Speed and Academic Fluency in Childhood Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only

Objective:The purpose of this study using archival data was to examine processing speed (PS) and its relation with academic fluencies in children who were diagnosed with, and treated with chemotherapy for, acute lymphoblastic leukemia (ALL) before vs. after five years of age. Chemotherapy is the first-line treatment for childhood leukemias, and the impact of cancer treatment on academic and global functioning may include a steady decline in functions over time (Baron &amp; Rey-Casserly, 2013). Specifically, this research initiative examined age and gender factors in PS and academic fluencies in this population.Participants and Methods:Sixty-eight participants (39 M, 29 F; mean age 10.6 years) diagnosed with ALL and who were previously treated with chemotherapy were included. Thirty-seven participants (23 M, 14 F) were &lt;5 years of age at the time of diagnosis and onset of chemotherapy, while 31 participants (16M, 15 F) were &gt;5 years of age at diagnosis and treatment. Participants ranged in age from 6 to 17 years at the time of their neuropsychological evaluation. Participants were given the WISC-V (PS subtests) and WJ-IV academic fluencies (math and reading). To evaluate research questions and hypotheses, correlational tests, independent samples t-tests, and analyses of variance (ANOVA) were used. Results at the p&lt; .05 level are reported.Results:There were significant correlations between PS and WJ math fluency (r=.510) and reading fluency (r=.392). Independent samples t-test analyses revealed that children who scored below 85 (standard score) on PS composite score demonstrated poorer performance on WJ math fluency (t(60)=-3.971, p=.000, d=1.065) and reading fluency (t(56)=-3.041, p=.004, d=0.896) compared to children whose PS scores were &gt; 85. For children whose PS scores were &lt;85, mean scores were in the low average range for WJ-IV math fluency (M=81.05) and reading fluency (M=84.50). No significant differences were found for age or gender in relation to PS and academic fluencies.Conclusions:Findings are important in highlighting the need for school accommodations in pediatric survivors of ALL. Processing speed is one of the most vulnerable functions impacted by cancer therapies and was positively correlated with reading and math fluencies in this study. Mean scores for math and reading fluencies were low average for age. In terms of academic accommodations, due to the slow processing speed of these boys and girls, regardless of their age at diagnosis and onset of chemotherapy, the provision for extra time for ALL survivors is recommended to ensure they are given the opportunity to maximize their learning potential and demonstrate their true academic abilities. Parents are encouraged to practice basic fluencies at home as early as possible. Inhospital and home-bound schooling supports are recommended to maintain educational progress. For children at higher risk for late effects and neurocognitive decline, rehabilitation similar to that which TBI survivors receive can be effective, as well. Future prospective research, including longitudinal tracking, with more homogeneous samples of pediatric survivors of ALL is expected to extend and refine findings of the present study.

Long-Term Kidney Outcomes of Pediatric Acute Lymphoblastic Leukemia Survivors

Long-Term Kidney Outcomes of Pediatric Acute Lymphoblastic Leukemia Survivors

Sarcopenia in long-term survivors of cancer in childhood and adolescence: A cross-sectional study of calf muscle mass by peripheral quantitative computed tomography with an examination of the muscle-bone unit.

Sarcopenia, a loss of systemic skeletal muscle mass (SMM), is prevalent in childhood cancer survivors and often accompanied by increased fat mass (sarcopenic obesity [SO]). We examined whether calf muscle cross-sectional area (CSA), measured by peripheral quantitative computed tomography (pQCT), can identify sarcopenia and SO in long-term survivors of pediatric acute lymphoblastic leukemia (ALL), and explored its relationship with adjacent bone geometry. Calf muscle CSA and CSA Z scores at the 38% tibia in 70 subjects (median survival 15years) were compared between sexes and ALL risk group, and their association with sarcopenia and SO evaluated. Relationships between bone strength and muscle mass were assessed further using linear regression and methods described by Schoenau etal. for evaluation of a functional muscle-bone unit. A calf muscle CSA Z score of less than or equal to zero is 73.81% sensitive and 84.62% specific for detecting sarcopenia defined by height-adjusted appendicular lean mass measured by dual-energy x-ray absorptiometry. No significant difference in CSA Z scores was noted between sexes or ALL risk groups; however, Z scores were markedly higher in those without SO (adjusted odds ratio 0.529, 95% confidence interval [CI]: 0.340-0.824). Ratios of calf muscle mass to height and total bone mineral content at the 38% tibia are "sufficient" and consistent with estimated reference ranges for a healthy population. CSA Z scores may represent a useful clinical measure of SMM and are predictive of SO in this population. Our results are supportive of a functional muscle-bone unit in long-term survivors of pediatric ALL.

Adaptive functioning and academic achievement in pediatric survivors of acute lymphoblastic leukemia: Associations with executive functioning, socioeconomic status, and academic support.

This study examines associations of functional outcomes (adaptive functioning and academic achievement) with executive functioning (EF), socioeconomic status (SES), and academic support in pediatric acute lymphoblastic leukemia (ALL) survivors. Fifty survivors of B-lineage ALL treated with chemotherapy-only (42% female, 76% NHW, ages 6-19) were evaluated on performance-based EF and academic achievement, and parent-rated EF and adaptive functioning. Area deprivation and child opportunity (i.e., SES) were extracted using census blocks and tracts. Academic support data were extracted from chart review. Compared to population norms, pediatric ALL survivors demonstrated significantly lower overall adaptive skills and performance in word reading and math calculation (all p ≤ .011). Frequencies of impairment were significantly elevated on all adaptive scales and in math calculation compared to the population (all p ≤ .002). Parent-rated EF significantly predicted overall adaptive skills (p < .001), while performance-based EF significantly predicted word reading and math calculation (all p < .05). Adaptive functioning was not associated with neighborhood-specific variables or academic support. However, academic support predicted word reading (p < .001), while area deprivation and academic support predicted performance-based EF (all p ≤ .02). Screening of functional outcomes, targeted intervention, and neuropsychological monitoring are necessary to support pediatric ALL survivors' neurocognitive and psychosocial development.

Changed cortical thickness and sulcal depth in pediatric acute lymphoblastic leukemia survivors treated with chemotherapy only.

The purpose of this study is to observe the changes of cortical morphological characteristics and their potential contribution to cognitive function in ALL survivors by using surface-based morphometry (SBM). Using SBM analysis, we calculated and compared group differences in cortical thickness, sulcal depth, gyrification, and fractal dimension of the cerebral cortex between 18 pediatric ALL survivors treated on chemotherapy-only protocols and off treatment within 2years, and 18 healthy controls (HCs) with two-sample t-tests [P < 0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical characteristic values and cognitive function parameters were investigated with partial correlation analysis, taking age as a covariate. We found decreased cortical thickness mainly located in the prefrontal and temporal region, and increased sulcal depth in left rostral middle frontal cortex and left pars orbitalis in the ALL survivors compared to HCs. There were no statistically significant differences in the gyrification and fractal dimension between the two groups. In ALL survivors, cortical thickness and sulcal depth of above areas values revealed no significant correlation with the cognitive function parameters. In conclusion, pediatric ALL survivors show decreased cortical thickness in prefrontal and temporal regions, and increased sulcal depth in prefrontal region. These results suggest that SBM-based approach can be used to assess changes of cortical morphological characteristics in pediatric ALL survivors.

Association of markers of inflammation on attention and neurobehavioral outcomes in survivors of childhood acute lymphoblastic leukemia.

Survivors of childhood acute lymphoblastic leukemia (ALL) are at-risk of developing cognitive impairment and neurobehavioral symptoms. Inflammation induced by a compromised health status during cancer survivorship is proposed as a pathophysiological mechanism underlying cognitive impairment in cancer survivors. To evaluate the associations of biomarkers of inflammation with attention and neurobehavioral outcomes in survivors of childhood ALL, and to identify clinical factors associated with biomarkers of inflammation in this cohort. We recruited patients who were diagnosed with ALL at ≤ 18 years old and were currently ≥5 years post-cancer diagnosis. The study outcomes were attention (Conners Continuous Performance Test) and self-reported behavioral symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling molecules that are associated with neurodegenerative diseases. The final panel of the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1β, and tumor necrosis factor-α. Biomarker levels were rank-ordered into tertiles based on the sample distribution. Multivariable general linear modeling was used to test for associations between biomarkers and study outcomes in the overall cohort and stratified by gender. This study included 102 survivors (55.9% males, mean[SD] age 26.2[5.9] years; 19.3[7.1] years post-diagnosis). Survivors within top tertiles of IFN-γ (Estimate =6.74, SE=2.26; P=0.0037) and IL-13 (Estimate =5.10, SE=2.27; P=0.027) demonstrated more inattentiveness. Adjusting for age, gender and treatment, more self-reported thought (Estimate=3.53, SE=1.78; P=0.050) and internalizing problems (Estimate =6.52, SE=2.91; P=0.027) correlated with higher IL-8. Higher levels of IL-13 (RR = 4.58, 95% CI: 1.01-11.10) and TNF-α (RR = 1.44, 95% CI: 1.03-4.07) were observed in survivors had developed chronic health conditions (n=26, 25.5%). The stratified analysis showed that association of IFN-γ with attention was stronger in male survivors than in female survivors. Inflammation due to cancer-related late effects may potentially be mechanistic mediators of neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can potentially be applied to assess or monitor the effectiveness of interventions, particularly behavioral interventions, in improving cognitive outcomes in survivors. Future work includes understanding the underlying gender-specific pathophysiology behind functional outcomes in the population.

Making sense of the cancer journey: Pediatric cancer survivors' and their parents' autobiographical memories.

Youth diagnosed with acute lymphoblastic leukemia (ALL) and their caregiver's experience a myriad of challenges in all domains of health that extend beyond treatment. Yet, little is known about how the cancer experience, and recollections associated with the experience, impact survivorship. We explored pediatric ALL survivors' and their caregivers' autobiographical memories of the cancer experience from diagnosis onwards. Survivors of ALL, and one of their caregivers, were recruited through a local clinic. Survivors and their caregivers completed a demographic survey and semi-structured, private, one-on-one interviews. Demographic information were analyzed using descriptive statistics. Interviews were transcribed verbatim and analyzed using reflexive thematic analysis at the level of the individual and dyad. Insights from survivors (N = 19; Mage = 15.3years) and their caregivers (n = 19; Mage = 45.4years) were captured. Analyses generated two themes contingent on role (i.e., survivor or caregiver): (1) It is hard to recall my cancer experience and (2) We did as much as we could to manage our child's cancer experience and two unified themes (present in both survivors and their caregivers): (3) It took a village to get through the cancer experience and (4) The cancer diagnosis and experience has had a lasting impact. Findings highlight the varied and long-lasting ways cancer impacts survivors of pediatric ALL and their caregivers. Survivors had difficultly remembering their experience or felt that information was withheld and were acutely aware of their caregiver's distress. Caregivers were cautious and intentionally limited the information they shared. Survivors desired to be included within, or told about, decisions related to their healthcare and were acutely aware of their caregiver's distress. Efforts should be made to communicate with survivors (from diagnosis onward) openly and to consider strategies to minimize the short- and long-term impacts of pediatric ALL among survivors and their caregivers.

Experience of WhatsApp uses in the follow-up of pediatric acute lymphoblastic leukemia survivors during the COVID-19 pandemic

Experience of WhatsApp uses in the follow-up of pediatric acute lymphoblastic leukemia survivors during the COVID-19 pandemic

Endothelial nitric oxide synthase gene polymorphism (786T/C) in childhood acute lymphoblastic leukemia survivors

Objectives to detect eNOS gene polymorphism and its relation to cardiovascular complications in pediatric acute lymphoblastic leukemia (ALL) survivors. Methods CBC, renal and liver function tests, lipid profile, Carotid artery Intima Media Thickness (CIMT) and Brachial artery Intima Media Thickness (BIMT). eNOS gene polymorphism were done in 40 childhood ALL survivors and 40 controls. Results there was no significant difference between survivors and control groups regarding 786T/C polymorphism. There was significant increase in serum Cholesterol, TGs, LDL, VLDL and HbA1c in the TC and CC group more than the TT group while there was significant decrease in serum HDL in the TC and CC group more than the TT group. There was no significant difference as regards echocardiography findings between different polymorphism of 786T/C but there was a significant difference between 786T/C groups as regard to the carotid and brachial arteries intima media thickness (IMT) measurements being significantly higher in the TC and CC group more than the TT group. Conclusion : Carotid and brachial arteries intima media thickness measurements were higher in the survivors when compared to healthy controls. eNOS gene polymorphism may play a role in modifying or developing CVD in pediatric ALL survivors.

Detecting Sarcopenic Obesity in Survivors of Pediatric Acute Lymphoblastic Leukemia: An Exploration of Body Mass Index and Triponderal Mass Index as Potential Surrogate Markers.

Survivors of pediatric acute lymphoblastic leukemia (ALL) often have altered body composition secondary to treatment effects, including sarcopenic obesity (SO), which increases the risk of both metabolic complications and frailty. SO is difficult to detect without using advanced imaging techniques to which access is often limited. To explore whether common clinical indices can reliably identify the presence of SO in a cohort of long-term survivors of ALL, the discriminatory capacity of body mass index (BMI) or triponderal mass index (TMI, kg/m 3 ) for detecting SO was assessed. Thresholds of BMI and TMI associated with overweight or obesity status had poor sensitivity (<50%) and specificity for detecting SO. Total misclassification rates at these thresholds exceeded 50% and positive likelihood ratios were nonsignificant. Notably, TMI is more strongly correlated with elevated adiposity than is BMI in this survivor population ( R2 =0.73 vs. 0.57), suggesting further exploration is warranted. Our study is limited by the sample size, precluding detailed regression analysis. This study highlights the challenges of identifying SO in survivors of pediatric ALL using common clinical indices. Prospective evaluation of additional potential surrogate markers in survivors, in conjunction with the component features of SO, should be a key focus of future research.

Assessment of metabolic syndrome parameters in pediatric acute lymphoblastic leukemia survivors.

This study aims to demonstrate the prevalence of metabolic syndrome parameters and to investigate their relationship with body mass index in pediatric acute lymphoblastic leukemia survivors. The cross-sectional study was conducted between January and October 2019 at the Department of Pediatric Hematology and comprised acute lymphoblastic leukemia survivors who had been treated between 1995 and 2016 and had been off treatment for at least 2 years. The control group included 40 healthy participants who were matched for age and gender. The two groups were compared in terms of various parameters (BMI [body mass index], waist circumference, fasting plasma glucose, HOMA-IR [Homeostatic Model Assessment-Insulin Resistance], etc.). Data were analyzed using Statistical Package for the Social Sciences (SPSS) 21. Of the 96 participants, 56 (58.3%) were survivors and 40 (41.6%) were controls. Among the survivors, there were 36 (64.3%) men, whereas the control group had 23 (57.5%) men. The mean age of the survivors was 16.67 ± 3.41 years, whereas the mean age of the controls was 15.51 ± 4.2 years (P > 0.05). Multinomial logistic regression analysis showed that cranial radiation therapy and female gender were associated with overweight and obesity (P < 0.05). A significant positive correlation was found between BMI and fasting insulin, in survivors (P < 0.05). Disorders of the metabolic parameter were found to be more common among acute lymphoblastic leukemia survivors than among healthy controls.

Abstract 2003: Poor diet quality is associated with immune aging in survivors of pediatric acute lymphoblastic leukemia

Abstract Rationale and objectives: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Despite a 90% five-year survival rate, survivors of childhood ALL often suffer from late effects, including cardiometabolic disorders. Contributing factors such as inflammation and oxidative stress, combined with drug treatments, can induce premature aging and cellular senescence with a significant impact on cardiometabolic disorders. Premature aging can lead to decreased thymic T-cell production, resulting in decreased circulation of T-cell receptor excision circles (TRECs). Because diet has been associated with cardiometabolic disorders, we hypothesized that the quality of diet in children who had survived ALL was related to the immune aging biomarker TREC, in concert with inflammatory status. Methods: Adolescent and young adult survivors of pediatric ALL of the PETALE cohort (n=241, 22.1 ± 6.3 years at diagnosis, 49.4% male) were examined in their profile for TREC levels (by qPCR) and for adherence to 6 diet quality indices. Results: Adjusted linear regressions revealed that the Healthy Diet Indicator (HDI) was associated with TREC levels (β=50.0, p=0.005, adjusted p=0.03). After performing a conceptual relational analysis (CAR) for data mining of various biomarkers of inflammation, oxidative stress, endotoxemia, and endothelial or adipose dysfunction; interleukin-6 (IL-6) and C-reactive protein (CRP) were found to be negatively associated with TREC levels (β= -80 and -80.1, p=0.017 and 0.026, respectively) but not with HDI. Further analysis revealed that IL-6 and CRP levels were moderators, but not mediators, of the association between HDI and TREC. Conclusion: This study supports the positive impact of a healthy diet on premature immune aging and the moderating role of inflammation in this association. Citation Format: Abderrahim Benmoussa, Tibila Kientega, Sophia Morel, Guillaume Cardin, Sophie Bérard, Mickael wajnberg, Petko Valtchev, Alexandre Blondin-Masse, Daniel Curnier, Maja Krajinovic, Caroline Laverdière, Daniel Sinnett, Emile Levy, Sophie Marcoux, Francis Rodier, Valérie Marcil. Poor diet quality is associated with immune aging in survivors of pediatric acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2003.

Comparative Analysis of Cognitive, Motor, and Visual-Motor Functions in Pediatric Acute Lymphoblastic Leukemia Survivors With and Without Allogeneic Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for pediatric high-risk acute lymphoblastic leukemia (ALL) survivors. Still, both the disease and treatment often impair cognitive and motor functions, and HSCT is a risk factor for long-term deficits. The study aimed at investigating the effect of HSCT on cognitive, motor, and visual-motor functions. Two groups were enrolled: The first group received HSCT treatment, and the second group did not. Sixty-five ALL survivors participated in the study (ages: 7-17). Twenty-one of participants who underwent HSCT comprised the first group. We implemented tests from Cambridge Neuropsychological Test Automated Battery, Wechsler Intelligence Scale for Children, and Test of Memory and Learning to estimate cognitive functions, Bruininks-Oseretsky Test of Motor Proficiency to estimate motor functions, and Beery-Buktenica Developmental Test to estimate visual perceptual and visual motor functions. As independent variables for analysis we chose group (HSCT+/-), age at diagnosis, and current age. MANCOVA test demonstrated significant effect of current age on cognitive functions (partial η2 = 0.55) and significant effect of HSCT treatment on motor functions (partial η2 = 0.19). Current age also had moderate effect on visual-motor functions (partial η2 = 0.11). Significant differences were found in most cognitive, motor, and visual-motor tests' results between the two groups, with HSCT+ group demonstrating poorer performance. This study has several limitations, including small sample size, potentially mismatched groups, imbalanced gender ratio. Still, the findings underline the importance of considering late effects of HSCT, and age when designing rehabilitation programs.

Left ventricular function in pediatric all survivors using speckle-tracking echocardiography and its relation to N-terminal brain natriuretic peptide

The aim of the present research is to investigate cardiac abnormalities using plasma N-terminal pro brain natriuretic peptide (NT-proBNP) and speckle-tracking echocardiography in asymptomatic pediatric acute lymphoblastic leukemia (ALL) survivors who received cardiotoxic drugs during their treatment. The Institutional Review Board (IRB) of the Menoufia Faculty of Medicine approved the study. Research work was performed in accordance with the Declaration of Helsinki. 40 pediatric ALL survivors and 25 healthy children were enrolled. Complete blood cell count, renal function tests and liver function tests, iron &amp; lipid profile, fasting blood sugar and plasma NT-proBNP level in addition to conventional and speckle-tracking Echocardiography were done. NT-proBNP was highly more significant in survivors than controls. Cardiac parameters as LV global longitudinal systolic peak strain (GLPS) of the three apical views, the GLPS of apical four chamber view (GLPS-A4C), the GLPS of apical two chamber view (GLPSA2C), the GLPS of apical long axis view (GLPS-LAX), and the “NT-proBNP levels were significantly higher in survivors when compared to controls”. NT-proBNP and 2-D speckle tracking echo show promise in detecting cardiac dysfunction in childhood cancer survivors beyond what is detected by conventional echocardiography. So, it should be added to the follow-up studies of CCS.