Survivors Of Childhood ALL Research Articles

Contribution of Fatigue to Cognitive Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors

Late effects such as neurocognitive issues and fatigue have been reported in childhood acute lymphoblastic leukemia (cALL) survivors. Yet, their association is often poorly understood. In this study, we wished to (1) describe neurocognitive difficulties and fatigue in a well-characterized cohort of long-term cALL survivors and (2) explore the risk of having neurocognitive deficits as a function of fatigue. Childhood ALL survivors (N = 285) from three Canadian treatment centers completed the DIVERGT battery of cognitive tests and the PedsQL Multidimensional Fatigue Scale. We performed logistic regressions to assess the risk of a survivor to show cognitive deficits (<2.0 SD) depending on their fatigue levels. At least one cognitive deficit on the DIVERGT was present in 31% of participants. Domains primarily affected were working memory, fine motor skills, and verbal fluency. Sleep/rest fatigue in youths was higher than norms (d = 0.35). The risk for cognitive deficits increased independently with levels of fatigue in the domains of cognitive speed and flexibility, working memory, and verbal fluency. For every 10-point increase on general or sleep/rest fatigue on the 0-100 scale, there was a median +23–35% risk of showing a deficit among the 7 tasks significantly associated with fatigue. Fatigue may constitute a complementary target when searching to mitigate cognitive issues in this population.

Physiological stress reactivity in pediatric cancer survivors treated with chemotherapy.

Children who experience early life stress demonstrate changes to their stress responses, which may modulate long-term health. Childhood cancer presents significant stress during diagnosis, treatment, and survivorship. We hypothesized that children who have completed chemotherapy treatment for ALL will demonstrate altered hormone patterns in response to a stressor compared with healthy controls. Twelve pediatric ALL survivors and 12 healthy controls completed the Trier Social Stress Test. Salivary samples, heart rate, and self-report ratings of stress were collected at baseline, pretest, and posttest. Between group comparison showed baseline (interleukin [IL]-8) was significantly higher in the survivor group versus controls (survivors: 89.9, 40.1-544.9pgml-1 ; controls: 30.7, 5.6-241.9pgml-1 , p=.001) as was peak (IL-8) (survivors: 147.1, 71.6-1177.6pgml-1 ; controls: 75.5, 28.6-698.6pgml-1 ). Peak salivary alpha-amylase (sAA) concentration was significantly lower in the survivor group (survivors: 69.3, 19.4-195.5Uml-1 ; controls: 91.2, 27.7-213.7Uml-1 ; p=.04). Repeated measures ANOVA revealed significant main effects for time on cortisol (F(2.35, 50.81) =5.9, p<.01), sAA (F(1.56, 33.17) =6.6, p<.01), stress ratings (F(3.42, 88.14) =53.4, p<.001), and heart rate (F(8, 83) =16.8, p<.05). Significant main effects for group were observed for IL-8 (F(1, 23) =8.2, p<.01) and tumor necrosis factor-α (F(1, 23) =6.8, p<.05). Significant interaction effects for group×time were found for sAA (F(5, 106) =2.8, p<.05). Our results indicate that childhood ALL survivors have similar responses to stress as healthy controls, but lower sympatho-adrenal-medullary reactivity. Therefore, altered stress regulation may present a pathway modulating long-term health in this population.

Neurocognitive outcomes in survivors of early adolescent and young adult (eAYA) hematologic cancers from the Childhood Cancer Survivor Study (CCSS).

10029 Background: Neurocognitive impairment in eAYA hematologic cancer survivors has not been well described, despite intensive neurotoxic therapies. We examined prevalence and risk for such impairment in hematologic cancer survivors diagnosed during eAYA compared to a younger age. Methods: We identified 1,213 eAYA (diagnosed at 15-21 years; median [range] follow-up age 40 [30-54]) and 4,538 childhood (diagnosed at &lt;15 years; median age 30 [17-48]) survivors of ALL (n= 301 vs 3274), AML (n= 77 vs 424), and Hodgkin lymphoma (HL; n= 835 vs 840) from the CCSS (diagnosed 1970-1999) who completed the Neurocognitive Questionnaire. Impairment was defined as a score &gt;90% of normative data in task efficiency (TE), organization (Org), memory (Mem), and emotional regulation (ER) domains. 1,014 age-matched siblings were controls. Treatment by diagnosis group, chronic health conditions, health status and health behaviors were examined as risk factors for neurocognitive impairment using multivariable logistic regression. Adjusted odds ratios (ORs) and corresponding 95% CI are reported. Results: Prevalence of neurocognitive impairment (≥1 impaired domain) was similar for eAYAs and childhood survivors of HL (31.0% vs 29.6%, p=0.54) and AML (36.4% vs 40.3%, p=0.51), although eAYA AML survivors were more likely to have impaired Mem (OR=2.3, 95% CI 1.0-5.4). eAYA ALL survivors were less likely to have neurocognitive impairment than childhood ALL survivors (28.2% vs 38.5%, p&lt;.001) due to lower risk for impaired TE (OR=0.7, 95% CI 0.4-1.0) and Org (OR=0.5, 95% CI 0.4-0.9). No factors, including cranial radiation (RT), explained the rate differences. Treatment by diagnosis group (including cranial RT in ALL, chest RT in HL, and salvage therapy use) was not consistently associated with neurocognitive impairment in eAYA survivors. However, anthracycline dose ≥120mg/m2 was a risk factor for impaired ER (OR=6.0, 95% CI 2.0-17.9) only in eAYA ALL survivors. Presence of a neurologic health condition was associated with impairment in all 4 domains in eAYA (ORs ranged 1.7-2.9) and childhood cancer survivors (ORs ranged 1.9-5.3). eAYA survivors with a respiratory condition were more likely to have impaired TE (OR=2.1, 95% CI 1.2-3.8). Being in good general health was associated with less impairment across all 4 domains for eAYA (ORs ranged 0.2-0.4) and childhood survivors (ORs ranged 0.3-0.5). eAYA survivors who never smoked were less likely to have impaired ER (OR=0.4, 95% CI 0.2-0.6) than those who smoke. Conclusions: Survivors of hematologic cancers diagnosed during eAYA are susceptible to neurocognitive impairment at rates similar to those diagnosed at younger ages. Having comorbidities and being in fair/poor general health are risk factors for impairment. Higher anthracycline exposure in ALL survivors diagnosed during eAYA was the only therapy associated with impairment rates.

Evaluation of endocrine and cardiac complications in survivors of childhood acute lymphoblastic leukemia: A single center study from south Punjab.

Objectives: The objective of our study was to evaluate the endocrine and cardiac complications in survivors of childhood ALL. Study Design: Descriptive Cross Sectional study. Setting: Department of Pediatric Hematology-oncology, Endocrinology and Cardiology at The Children Hospital &amp; Institute of Child health Multan (CH&amp; ICH). Period: January 2019 to June 2019. Material &amp; Methods: Sixty patients were enrolled after taking informed consent from patient/parents. Endocrine complications include (growth failure, overweight/obesity, hyperlipidemia, thyroid disorders, precocious puberty) and cardiac complications include hypertension and low ejection fraction were evaluated. Results: Out of 60 ALL survivors 32 were males (53.3%) and 28 were females (46.7%). At diagnosis patient’s age range was 7-17 years with median age of 11.6 years. At study median age was 17 years with age range of 13 to 23 years. Among our ALL survivors 56.6% had one complication and 25% had multiple problems. Obesity (25%), overweight (20%) and hyperlipidemia (26.4%) were the three common complications followed by short stature (5%), thyroid disorders (3.3%) and hypertension (3.3%). Conclusion: We report high prevalence (56.6%) of these complications from south Punjab. Therefore extended follow up of ALL survivors is needed in order to identify an abnormality and timely treatment and improved quality of life.

Abstract B62: The need to improve exercise prescriptions to support care in pediatric oncology

Abstract Purpose: Cancer survivors’ exposure to chemotherapeutic agents leads to multiple long-term side effects with a decrease in their cardiorespiratory fitness. The first aim was to determine whether cardiorespiratory fitness and physical activity levels were lower among survivors than healthy Canadians, while the second aim was to report associations between genetic variants and cardiorespiratory fitness in survivors. Methods: Cardiorespiratory fitness (VO2peak) and moderate to vigorous physical activity (MVPA) were compared between childhood ALL survivors (N=221) and healthy Canadians (N=825). We performed whole-exome sequencing in survivors. Germline variants (both common and rare) in a selected set of trainability genes were analyzed for an association with cardiorespiratory fitness. Results: Survivors’ VO2 peak was found to be 22% lower than healthy Canadians. The cardiorespiratory fitness level was different between survivors and healthy Canadians despite a clinically equivalent level of MVPA. Positive associations between the cardiorespiratory fitness level and trainability genes (TTN, LEPR, IGFBPI, and ENO3 genes) were reported, especially in female survivors with a low cardiorespiratory fitness level. Conclusion: The cardiorespiratory fitness was significantly lower in survivors, which can be associated with variants in genes related to subjects’ trainability. At this time, it appears that more physical activity would be beneficial to survivors to achieve the same benefits as the healthy population. However, the optimal amount of physical activity needed to reach these benefits is not yet clear. The survivors’ responder or nonresponder status several years after the end of the treatments is unknown. This study has important implications for the field of exercise in oncology. Citation Format: Maxime Caru, Kateryna Petrykey, Mariia Samoilenko, Simon Drouin, Valérie Lemay, Laurence Kern, Lucia Romo, Patrick Beaulieu, Pascal St-Onge, Laurence Bertout, Geneviéve Lefebvre, Gregor Andelfinger, Maja Krajinovic, Caroline Laverdière, Daniel Sinnett, Daniel Curnier. The need to improve exercise prescriptions to support care in pediatric oncology [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B62.

Exercise Is Medicine: Need To Improve Exercise Prescriptions In Pediatric Oncology To Help Female Survivors

PURPOSE: About 65% of childhood survivors who were exposed to chemotherapeutic agents during treatment suffer from multiple late adverse effects. Even though both males and females were treated with chemotherapy during their cancer, the distinction between them is not always taken into consideration in an exercise oncology context. This study aims to assess cardiorespiratory fitness and moderate to vigorous physical activity (MVPA) of survivors in comparison to healthy participants. Genetic associations with cardiorespiratory fitness levels were reported to provide a better understanding of how physiological parameters differ in both males and females, and to find out whether gender and genetic parameters have an impact on their cardiorespiratory fitness. METHODS: Germline variants in a selected set of genes were analyzed for an association with cardiorespiratory fitness. Whole-exome sequencing in survivors (N=239) was performed. Cardiorespiratory fitness and MVPA data were compared between childhood ALL survivors (N=221) and healthy participants (N=825). Additional analyses were performed to study the physiological differences between males and females. RESULTS: We found that female survivors (27.7±6.7mL·kg-1·min-1) were more affected than males (36.8±7.1mL·kg-1·min-1) by low cardiorespiratory fitness. For a clinically equivalent level of MVPA, cardiorespiratory fitness was significantly lower in female survivors (27.7±6.7mL·kg-1·min-1), compared to healthy females (37.0±7.6mL·kg-1·min-1). Female survivors' physical deconditioning seems to increase with age. Female survivors have significant genetic associations between their cardiorespiratory fitness and their trainability genes (LEPR, IGFBPI and ENO3 genes) that play an important role in the functioning of their skeletal and cardiac muscles. CONCLUSIONS: Female survivors are at higher risk than males to have an impairment in their cardiorespiratory fitness and represent at-risk patients in regard to their genetic dispositions. The promotion of physical activity needs to be encouraged through the care system with the involvement of health care professionals in pediatric oncology. An evidence-based medicine approach is essential to help females to improve their cardiorespiratory fitness through physical activity.

Gut Microbiome in Survivors of Childhood Acute Lymphoblastic Leukemia

PurposeAcute lymphoblastic leukemia (ALL) is the most common cancer in childhood and has a high treatment success rate. However, survivors of childhood ALL have a high prevalence of chronic medical illnesses, such as metabolic syndrome. Dysbiosis in the gut microbiome is associated with metabolic derangement and disease risk. Chemotherapy and antibiotics increase gut microbiome dysbiosis. We tested the hypothesis that ALL treatment can cause alterations in the gut microbiome that persist in survivorship.MethodStool samples were collected on fecal occult blood test cards from 38 survivors between 2-18 years of age who were >1 year off therapy for ALL. 16 stool samples from healthy siblings age 2-18 years were collected from 14 families as controls. Clinical data including anthropometrics, antibiotic use, and probiotic use were collected. DNA was extracted and sequenced using a modified Illumina 16S Metagenomics Sequencing Library Preparation protocol for analysis of hypervariable region V4. A single rarefaction was performed at 4,897 removing 2 samples with low mapped read counts. Alpha and beta (Bray) diversities were calculated; Wilcoxon rank-sum test was used to compare the alpha diversities between groups, as well as the beta diversities within and between groups. Wilcoxon signed-rank test was used to compare the alpha diversity between survivors and their matched siblings. Finally, read counts for each Operational Taxonomic Unit (OTU) was normalized and tested for differential abundance using edgeR, assuming a negative binomial model.ResultsSignificant differences in the abundance of taxa were found, with the most notable being the depletion of Faecalibacterium in survivors (FDR= 0.0004). Figure 1 shows a heatmap with the complete linkage clustering method on the Euclidean distance using the 13 OTUs with statistically significant (FDR<0.05) differences between survivors and siblings (Table 1). When compared to their respective siblings, survivors exhibited decreased alpha diversity using four metrics (Observed, Shannon, Simpson, Fisher), but these results did not meet statistical significance. Significant differences were not observed in alpha diversity within survivors between different clinical categories (antibiotic usage, probiotic usage, disease risk, age at diagnosis and time off treatment). Stool microbiome was more similar within a family than between families (P = 0.00079).ConclusionDifferences in the relative abundance of certain taxa were found between survivors and siblings. Specifically, Fecalibacterium was depleted in survivors, which has also been previously observed in older populations of childhood ALL survivors. This study shows that these microbiome changes are present in ALL survivors during childhood, and should be evaluated longitudinally for association with the chronic medical illnesses seen in ALL survivors in adulthood. Early interventions to restore the gut microbiome in ALL patients may potentially ameliorate the risk of long-term adverse health outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Obesity and Altered Body Composition in Childhood ALL Survivors

Obesity and Altered Body Composition in Childhood ALL Survivors

Risk of hospitalization among survivors of childhood and adolescent acute lymphoblastic leukemia compared to siblings and a general population sample

BackgroundAcute Lymphoblastic Leukemia (ALL) has a high survival rate, but cancer-related late effects in the early post-treatment years need documentation. Hospitalizations are an indicator of the burden of late effects. We identify rates and risk factors for hospitalization from five to ten years after diagnosis for childhood and adolescent ALL survivors compared to siblings and a matched population sample. Methods176 ALL survivors were diagnosed at ≤22 years between 1998 and 2008 and treated at an Intermountain Healthcare facility. The Utah Population Database identified siblings, an age- and sex-matched sample of the Utah population, and statewide inpatient hospital discharges. Sex- and birth year-adjusted Poisson models with Generalized Estimating Equations and robust standard errors calculated rates and rate ratios. Cox proportional hazards models identified demographic and clinical risk factors for hospitalizations among survivors. ResultsHospitalization rates for survivors (Rate:3.76, 95% CI=2.22–6.36) were higher than siblings (Rate:2.69, 95% CI=1.01–7.18) and the population sample (Rate:1.87, 95% CI=1.13–3.09). Compared to siblings and population comparisons, rate ratios (RR) were significantly higher for survivors diagnosed between age 6 and 22 years (RR:2.87, 95% CI=1.03–7.97 vs siblings; RR:2.66, 95% CI=1.17–6.04 vs population comparisons). Rate ratios for diagnosis between 2004 and 2008 were significantly higher compared to the population sample (RR:4.29, 95% CI=1.49, 12.32), but not siblings (RR:2.73, 95% CI=0.54, 13.68). Survivors originally diagnosed with high-risk ALL did not have a significantly higher risk than siblings or population comparators. However, high-risk ALL survivors (Hazard ratio [HR]:3.36, 95% CI=1.33–8.45) and survivors diagnosed from 2004 to 2008 (HR:9.48, 95% CI=1.93–46.59) had the highest risk compared to their survivor counterparts. ConclusionsFive to ten years after diagnosis is a sensitive time period for hospitalizations in the ALL population. Survivors of childhood ALL require better long-term surveillance.

Motor Function in Pediatric ALL Survivors after Chemotherapy-Only

Background: Up to 40% of childhood ALL survivors suffer from fine-motor problems interfering with school performance and daily life. So far, drawing and handwriting skills as well as manual dexterity are not well understood in childhood ALL survivors after chemotherapy-only. Until now, ataxia or tremor have not been tested with standardized tools in chemotherapy-only survivors.

Neurocognitive Outcome and White Matter Anisotropy in Childhood Acute Lymphoblastic Leukemia Survivors Treated with Different Protocols

Neurocognitive outcome affects the quality of life of ALL survivors. This study is aimed to assess the prevalence of neurocognitive dysfunction by psychometric and imaging tools in survivors of childhood ALL, treated with 3 different protocols and the effect of time elapsed since the end of chemotherapy. Sixty-two ALL survivors aged 6–18 years and treated in the period 1997–2007 and 60 healthy age and sex matched controls were subjected to neurocognitive testing using Wechsler Intelligence Scale for Children, Benton visual retention (BVRT) and Trail Making test (TMT), followed by diffusion weighed and diffusion tensor MRI for calculation of fraction anisotropy (FA). Survivors underwent revision of protocol and type of CNS therapy. Three different protocols were used: modified BFM 83, BFM 90, and CCG. Survivors treated with modified CCG protocol showed a significant decrease in all cognitive tests compared to control (p<.05); BFM 90 group had a significant lower IQ and longer TMT compared to both control and BFM 83 group and no significant difference was found in results of cognitive tests between BFM 83 and control group. Frontal FA was lower in CCG treated group compared to control, BFM 90 and BFM 83 groups (p<.05); meanwhile it was significantly lower in BFM 90 and BFM 83 groups compared to control group. We concluded that patients treated with modified CCG protocol showed the worst neurocognitive outcome among three assessed protocols. Frontal lobe FA might be an early marker for predicting the neurotoxicity in childhood ALL survivors.

Adequate endocrine and cardiovascular response to social stress in survivors of childhood acute lymphoblastic leukemia

Survivors of childhood ALL have been demonstrated to have increased morning cortisol levels compared to healthy controls. Information regarding the response of the HPA axis and the sympathetic nervous system to stress in childhood ALL survivors is not available. The present study aimed at assessing the endocrine and cardiovascular stress response in childhood ALL survivors and healthy controls by evaluating perceived stress on visual analog scales, by determining saliva cortisol, blood pressure and heart rate in response to the Trier Social Stress Test for Children (TSST-C). Fifty survivors who had completed their treatment for childhood ALL 57 (IQR 47.0-72.3) months before and 50 healthy age and sex matched controls were included. Exposure to the TSST-C induced a significant response of perceived stress, saliva cortisol and cardiovascular outcome variables in the total study group. These responses did not significantly differ between survivors of childhood ALL and healthy controls. We conclude that the endocrine and cardiovascular response to social stress are intact in survivors of childhood ALL.

Osteosarcoma Following Growth Hormone Therapy in Recurrent Acute Lymphoblastic Leukemia and Rapadilino Syndrome

A 16-year old Caucasian girl was evaluated for scoliosis 9 years after bone marrow transplant (BMT) and 13 years after her initial ALL diagnosis. A chest radiograph showed a lesion of the right third rib. Histopathology was consistent with a high-grade OS. She died 5 months after OS diagnosis. There is no family history of cancer. Prior therapy comprised BFM standard risk for de novo ALL, St. Jude Children’s Research Hospital regimen and cranial-spinal radiation for central nervous system (CNS) recurrence, Children’s Cancer Group (CCG) 1941, and matched unrelated allo-transplant (conditioned with TBI and thiotepa, cyclophosphamide, and ATG) for bone marrow recurrence. Two years after transplant GH therapy commenced. A 15-year-old Hispanic girl with RAPADILINO syndrome experienced left lower extremity pain. Magnetic resonance imaging (MRI) showed a destructive lesion and biopsy was consistent with OS. At 11 years of age short stature was diagnosed. Growth hormone therapy was started and discontinued once OS was diagnosed. There is no family history of cancer. The Childhood Cancer Survivor Study reported the 25-year follow-up among survivors of childhood ALL. The cumulative incidence of SMN of 5.2% (6.2% for those receiving radiation therapy) at 25 years from diagnosis [2]. St. Jude Children’s Research Hospital (SJCRH) investigators reported the incidence of SMN as a first event in 2169 patients treated between 1962 and 1998 [3]. The cumulative incidence of SMN was 4.17% at 15 years and 10.85% at 30 years. Two cases of OS constituting 1.2% of SMN were observed.

Abdominal aortic calcification in young adult survivors of childhood acute lymphoblastic leukemia: Results from the St. Jude Lifetime Cohort study

Abdominal aortic calcification (AAC), metabolic syndrome, and low bone mineral density (BMD) are risk factors for atherosclerotic disease and cardiovascular morbidity. We evaluated AAC in 662 adult survivors of childhood ALL (median age 31 years). AAC was present in 10% of subjects, metabolic syndrome in 36%, and low BMD in 29%. The adjusted odds ratio (OR) for AAC among women with metabolic syndrome was 2.3 (95% CL = 1.0, 4.3). The adjusted OR for AAC in men with low BMD was 3.1 (95% CL = 1.3, 7.3). A substantial proportion of adult survivors of childhood ALL have AAC and/or metabolic syndrome, suggestive of early atherosclerotic disease.

Post-Therapy Profile of BMI-for-Age of Indian Survivors of Pediatric Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma

Background: Obesity in pediatric ALL survivors is a well recognized late effect. Hence the present study examines the BMI-for-age of Indian childhood ALL and NHL survivors. Method: A retrospective study of 118 ALL/NHL survivors and 138 age sex matched was carried out. From the recorded heights and weights were body mass index (BMI) was computed. The survivor data was compared with 138 controls from the data set collected by investigators previously. Results: 82.8% of patients had BMI-for-age in 5th-84th percentile (healthy) at time of diagnosis and at inclusion in the study. Comparison of BMI of survivors with matched controls was not significant. However, The mean BMI-for-age for younger patients (3 to 12 years) was significantly higher than mean BMI-for-age of matched controls. Distribution of data by time elapsed from therapy was significant. Overweight/obesity was observed among the survivors who were off therapy for two years with increase in after four years post-therapy. Conclusion: Our preliminary study indicates late effects of therapy and points to the need of long term assessment of the survivors, even though majority of them were within the normal weight range.

Neurocognitive Outcome of Childhood ALL Survivors Using Three Different Protocols Over a Decade

Abstract 4226Patients with childhood ALL achieve long-term disease-free survival, making reducing complications of therapy of major concerns. The aim of this study was to assess the prevalence and degree of neurocognitive dysfunction in survivors of childhood ALL treated with different protocols and the effect of time since end of chemotherapy. Patients and methods:A cross-sectional study including 60 ALL survivors aged 5–16 years at enrollment; 2–9 years at diagnosis, CNS1, treated through 1998–2008 and regularly followed up in childhood cancer survivors clinic;. They were compared to 20 healthy age and sex matched controls. Grade of school, scholastic achievement in the previous year were reported followed by revision of hospital records including type and risk of ALL, protocol of treatment, number, type and dose of intrathecal chemotherapy, number and doses of high dose I.V methotrexate, data of cranial radiotherapy. Three different protocols were applied to these patients according to the time of diagnosis, patients diagnosed between January 1998 to December 2000 were treated with Modified BFM 83. Those diagnosed between January 2001 to June2004 were treated with BFM 90 protocol, and those diagnosed From July 2004 to June 2008 were treated with CCG 1991 for standard risk and CCG 1961 for high risk patients.Neurocognitive functions were tested using Wechsler Intelligence Scale for Children,Benton visual retention (BVR) test and Trail making test (part A and B were done. MRI Brain was performed to the patients and control group using diffusion weighed images and diffusion tensor magnetic resonance imaging (DTI). Results:Survivors treated with CCG protocol showed a significant decrease in all cognitive tests results compared to control (p<0.05). Survivors treated with BFM 90 protocol had a significant lower total IQ, verbal IQ, TMT-partA, compared to both control and survivors treated with Modified BFM 83, and a significant decrease in performance IQ, BVRT and TMT-partB compared to control only. No significant difference between results of cognitive tests in survivors treated with Modified BFM 83 and control group. Both left and right frontal cortex apparent diffusion coefficient (ADC) was significantly higher in CCG(.88±.060.91±.028) treated group compared to control(.695±.0018.684±.0018), BFM 90(.79±.071.76±.048) and modified BFM 83(.76±.030.83±.023×10−3mm2/s) groups (p<0.05) yet a significant decrease in FA of right frontal cortex only in CCG (.250±.039)treated group compared to control(.684±.0018), BFM 90(.450±.042) and Modified BFM 83(.41±.028) groups(p<0.05). FA of right frontal, was significantly lower in BFM 90 and Modified BFM 83 treated group compared to control group. No significant correlation was found between cognitive tests results with age at diagnosis, time since the end of therapy, total number of intrathecal injections, age at radiotherapy treatment, dose and time of radiotherapy. Cognitive tests didn't differ between survivors treated with triple intrathecal therapy(ITTT) compared to those treated with intrathecal methotrexate, yet significant decrease in FA of right hippocampus in survivors who received ITTT compared to survivors treated with intrathecal monotherapy, Conclusion:Neurocognitive dysfunction was a common sequelae of childhood ALL treatment. It was more related to protocol of therapy rather than the duration of follow-up since end of chemotherapy. Frontal lobe FA may be a clinically useful biomarker for the assessment of neurotoxicity in post-treatment childhood ALL survivors. Disclosures:No relevant conflicts of interest to declare.

Executive functions in aging adult survivors of childhood leukemia.

9011 Background: Survivors of childhood ALL are at risk for deficits in basic cognitive skills (e.g. attention, processing speed and working memory), typically beginning within five years of diagno...

“Chemobrain” in Survivors of Childhood ALL?

“Chemobrain” in Survivors of Childhood ALL?

"Chemobrain" in Survivors of Childhood ALL?

"Chemobrain" in Survivors of Childhood ALL?

Obesity in adult survivors of childhood acute lymphoblastic leukemia: A follow-up report from the Childhood Cancer Survivor Study

9518 Background: We previously reported an association between ≥ 20 Gy cranial radiotherapy (CRT) and obesity in adult survivors of childhood ALL. This follow-up study aimed to determine if, with time, (1) the prevalence of obesity and (2) the rate of BMI change were increased in ALL survivors in comparison with sibling controls. Methods: A longitudinal cohort comparing 1,451 adult survivors of childhood ALL (mean age 32.3 years) to 2,167 siblings of childhood cancer survivors (mean age 35.9 years). BMI was calculated from self- reported heights and weights and used to determine the prevalence of being overweight (25.0 ≤ BMI &lt; 30.0) or obese (BMI ≥ 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors compared to sibling controls. BMIs at baseline and follow-up (with a mean interval of 7.8 years) were used to calculate mean BMI increases per year occurring between these timepoints. Results: Age- and race-adjusted ORs for obesity among survivors compared with siblings are shown in the table . Notably, 10–19 Gy CRT was associated with an increased likelihood of being obese in comparison with siblings. In longitudinal analysis, survivors who were treated with CRT had a significantly greater net increase in BMI/year in comparison with siblings. At follow-up, 69.7% of females treated with ≥ 20 Gy CRT prior to the age of 10 were overweight (31.1%) or obese (38.6%). Conclusion: Cranial radiotherapy ≥ 10 Gy employed in the treatment of childhood ALL is strongly associated among both male and female survivors with increases in the prevalence of obesity and average BMI gains over time. Female survivors who received CRT ≥ 20 Gy, particularly those treated at a younger age, were most affected. [Table: see text] No significant financial relationships to disclose.