scholarly journals Sex-Specific Associations Between Chemotherapy, Chronic Conditions, and Neurocognitive Impairment in Acute Lymphoblastic Leukemia Survivors: A Report From the Childhood Cancer Survivor Study

2020 ◽  
Author(s):  
Ellen van der Plas ◽  
Weiyu Qiu ◽  
Brian J Nieman ◽  
Yutaka Yasui ◽  
Qi Liu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Childhood Cancer ◽  
Chronic Conditions ◽  
Lymphoblastic Leukemia ◽  
Neurocognitive Impairment ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Impaired Memory ◽  
Childhood Cancer Survivor Study ◽  
Task Efficiency

Abstract Background The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only. Methods This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided. Results Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92). Conclusion Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship.

scholarly journals Prevalence and Predictors of Neurocognitive Impairment in Long-Term Survivors of Childhood Hodgkin Lymphoma: A Report from the Childhood Cancer Survivor Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Annalynn M Williams ◽  
Mengqi Xing ◽  
Sedigheh Mirzaei Salehabadi ◽  
Yutaka Yasui ◽  
Matt J. Ehrhardt ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Emotional Regulation ◽  
Neurocognitive Impairment ◽  
Elevated Risk ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Chronic Health ◽  
Childhood Cancer Survivor Study ◽  
Task Efficiency ◽  
Long Term Survivors

Background: Long-term survivors of childhood Hodgkin lymphoma (HL) are at significant risk for cardiovascular, pulmonary, and endocrine morbidity in addition to subsequent cancers. Emerging evidence suggests that HL survivors may also experience persistent neurocognitive impairment, however the prevalence of neurocognitive impairment has not been well characterized. Further, little work has been done to examine how specific treatments or comorbidities are associated with these impairments. Methods: The current study included 1,760 survivors (52.0% female, mean[sd] 37.5 [6.0] years old, 23.6 [4.7] years from diagnosis) of childhood Hodgkin lymphoma and 3,180 sibling controls (54.5% female, 33.2 [8.5] years old) from the Childhood Cancer Survivor Study. Participants completed questionnaires assessing four domains of neurocognitive impairment (task efficiency, emotional regulation, organization, and memory). Impairment for each domain was defined as a score worse than the 90th percentile of community controls. Treatment exposures were abstracted from the medical record. Second malignancies (SMN) were self-reported and subsequently confirmed by pathology findings or medical record review. Chronic health conditions were self-reported and systematically graded according to the NCI CTCAE v4.3 (Grade 1 mild, Grade 2 moderate, Grade 3 severe/disabling, Grade 4 life-threatening). Generalized estimating equations were used to calculate risk of impairment in survivors compared with siblings adjusted for age, sex, and race. Among HL survivors, multivariable log-binomial regression was used to calculate risk of impairment associated with demographic, clinical, and treatment factors. Separate models examined risk associated with Grade 2+ chronic health conditions adjusted for age, sex, and race. Results: 10.8% of HL survivors reported impaired task efficiency (vs. 7.7% in siblings), 16.6% emotional regulation (vs. 11.5% in siblings), 12.1% organization (vs. 10.3% in siblings), and 8.1% memory (vs. 5.7% in siblings). Compared with siblings, survivors reported significantly higher risk of impairment in each of the four neurocognitive domains after adjusting for age, sex, and race (Table). Female survivors had elevated risk of impairment on emotional regulation (RR [95%CI] 1.4 [1.1,1.9)) and memory (2.0 [1.3,3.0]). Compared with white survivors (91.8% of the population), non-white survivors had higher risk of impairment in task efficiency (2.1 [1.2, 3.5]) and emotional regulation (1.7 [1.0,2.7]). Current smokers (12.3%) had higher risk of impairment in task efficiency (1.9 [1.2, 3.1]), emotional regulation (2.5 [1.7,3.7]), and memory (1.7 [1.0,3.0]). Having a late-relapse (>5 years from diagnosis) or a second malignancy (20.0%) was associated with elevated risk of impairment in task efficiency (1.6 [1.06,2.3]). While not statistically significant, anthracycline exposure (39.8%) was associated with higher risk of impairment in task efficiency (1.3 [0.7,2.2]) and memory (1.6 [0.9,3.0]). No statistically significant associations were noted for bleomycin, corticosteroids, or chest radiation. HL survivors with pulmonary morbidity (8.5%) had a higher risk of impairment on task efficiency (1.9 [1.2,3.0]) compared to those without. Cardiovascular conditions (32.9%) were associated with elevated risk of impairment in all domains (RR range from 1.5 to 2.1, all p<0.05, Table). Endocrine (54.3%) and neurologic conditions (6.6%) were associated with an increased risk of task efficiency, emotional regulation, and memory impairments (RR range from 1.4 to 5.5, all p<0.05, Table). Conclusions: Survivors experienced significantly more neurocognitive impairment compared to sibling controls. Among survivors, potentially modifiable risk factors such as smoking and chronic health conditions were associated with neurocognitive impairment while treatment exposures showed little association. Mitigation or prevention of smoking and chronic health conditions may improve neurocognitive functioning in HL survivors Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Longitudinal Changes in Obesity and Body Mass Index Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study

2008 ◽  
Vol 26 (28) ◽  
pp. 4639-4645 ◽  
Author(s):  
Edward G. Garmey ◽  
Qi Liu ◽  
Charles A. Sklar ◽  
Lillian R. Meacham ◽  
Ann C. Mertens ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Acute Lymphoblastic Leukemia ◽  
Childhood Cancer ◽  
Body Mass ◽  
Cancer Survivor ◽  
Comparison Group ◽  
Lymphoblastic Leukemia ◽  
Childhood Cancer Survivor ◽  
Childhood Cancer Survivor Study

Purpose We examined the rate of increase in the body mass index (BMI; kg/m2) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group. Methods Childhood Cancer Survivor Study (CCSS) is a retrospectively ascertained cohort study that prospectively tracks the health status of adults who were diagnosed with childhood cancer between 1970 and 1986 and a comparison group of siblings. Changes in BMI from baseline enrollment to time of completion of follow-up (mean interval, 7.8 years) were calculated for 1,451 ALL survivors (mean age, 32.3 years at follow-up) and 2,167 siblings of childhood cancer survivors (mean age, 35.9 years). Results The mean BMI of the CCSS sibling comparison group increased with age (women, 0.25 units/yr, 95% CI, 0.22 to 0.28 units; men, 0.23 units/yr, 95% CI, 0.20 to 0.25 units). Compared with CCSS siblings, ALL survivors who were treated with cranial radiation therapy (CRT) had a significantly greater increase in BMI (women, 0.41 units/yr, 95% CI, 0.37 to 0.45 units; men, 0.29 units/yr; 95% CI, 0.26 to 0.32 units). The rate of BMI increase was not significantly increased for ALL survivors who were treated with chemotherapy alone. Younger age at CRT exposure significantly modified risk. Conclusion CRT used in the treatment of childhood ALL is associated with a greater rate of increasing BMI, particularly among women treated with CRT during the first decade of life. Health care professionals should be aware of this risk and interventions to reduce or manage weight gain are essential in this high-risk population.

Obesity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

2003 ◽  
Vol 21 (7) ◽  
pp. 1359-1365 ◽  
Author(s):  
Kevin C. Oeffinger ◽  
Ann C. Mertens ◽  
Charles A. Sklar ◽  
Yutaka Yasui ◽  
Thomas Fears ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Lymphoblastic Leukemia ◽  
Adult Survivors ◽  
Childhood Cancer Survivor ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Radiation Doses ◽  
Cranial Radiation ◽  
Childhood Cancer Survivor Study

Purpose: To determine whether adult survivors (≥ 18 years of age) of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity and to assess patient and treatment variables that influence risk. Patients and Methods: A retrospective cohort of participants of the Childhood Cancer Survivor Study was used to compare 1,765 adult survivors of childhood ALL to 2,565 adult siblings of childhood cancer survivors. Body-mass index (BMI; kilograms per square meter), calculated from self-reported heights and weights, was used to determine the prevalence of being overweight (BMI, 25–29.9) 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 relative to the sibling control group. Results: The age- and race-adjusted OR for being obese in survivors treated with cranial radiation doses ≥ 20 Gy in comparison with siblings was 2.59 for females (95% CI, 1.88 to 3.55; P < .001) and 1.86 for males (95% CI, 1.33 to 2.57; P < .001). The OR for obesity was greatest among females diagnosed at 0 to 4 years of age and treated with radiation doses ≥ 20 Gy (OR, 3.81; 95% CI, 2.34 to 5.99; P < .001). Obesity was not associated with treatment consisting of chemotherapy only or with cranial radiation doses of 10 to 19 Gy. Conclusion: Cranial radiotherapy ≥ 20 Gy is associated with an increased prevalence of obesity, especially in females treated at a young age. It is imperative that healthcare professionals recognize this risk and develop strategies to enhance weight control and encourage longitudinal follow-up.

scholarly journals Racial/Ethnic Differences in Adverse Outcomes Among Childhood Cancer Survivors: The Childhood Cancer Survivor Study

2016 ◽  
Vol 34 (14) ◽  
pp. 1634-1643 ◽  
Author(s):  
Qi Liu ◽  
Wendy M. Leisenring ◽  
Kirsten K. Ness ◽  
Leslie L. Robison ◽  
Gregory T. Armstrong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Ethnic Differences ◽  
Childhood Cancer Survivors ◽  
Adverse Outcomes ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Childhood Cancer Survivor Study ◽  
Racial Ethnic

Purpose Childhood cancer survivors carry a high burden of treatment-related morbidity; however, race/ethnicity–specific risks of adverse outcomes are not well understood. Methods Data from the Childhood Cancer Survivor Study, a cohort of survivors of at least 5 years, were used to compare Hispanic (n = 750, 5.4%) and non-Hispanic black (NHB: n = 694, 5.0%) survivors to non-Hispanic white patients (NHW: n = 12,397, 89.6%) for late mortality, subsequent neoplasms, and chronic health conditions. Results NHBs and Hispanics reported lower socioeconomic status (SES) and higher prevalence of obesity, and NHBs reported higher prevalence of hypertension. NHBs had higher rate of all-cause mortality (relative rate [RR], 1.4; 95% CI, 1.1 to 1.9; P = .008), which was abrogated (RR, 1.0; 95% CI, 0.8 to 1.4; P = .9) after adjusting for SES. Nonmelanoma skin cancer was not observed among irradiated NHBs, and the risk was lower among Hispanic survivors (RR, 0.3; 95% CI, 0.1 to 0.7) compared with NHWs. Both NHBs and Hispanics demonstrated elevated risks for diabetes; these risks persisted after adjusting for SES and obesity (NHBs: RR, 2.8; 95% CI, 1.1 to 6.7; Hispanics: RR, 3.1; 95% CI, 1.5 to 6.4). NHBs were more likely to report cardiac conditions (RR, 1.8; 95% CI, 1.1 to 2.7), but the risk was attenuated after adjusting for cardiovascular risk factors. Therapeutic exposures did not affect racial/ethnic differences in mortality (all cause or cause specific), chronic health conditions, or subsequent neoplasms. Conclusion By and large, NHB and Hispanic childhood cancer survivors experience a comparable burden of morbidity and mortality to their NHW counterparts. The few differences in risk were explained by the racial/ethnic differences in socioeconomic status and/or cardiovascular risk factors.

Temporal trends in chronic disease among survivors of childhood cancer diagnosed across three decades: A report from the Childhood Cancer Survivor Study (CCSS).

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA10500-LBA10500 ◽  
Author(s):  
Todd M. Gibson ◽  
Sogol Mostoufi-Moab ◽  
Kayla Stratton ◽  
Dana Barnea ◽  
Eric Jessen Chow ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Childhood Cancer ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Wilms Tumor ◽  
Lymphoblastic Leukemia ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Malignant Neoplasms ◽  
Chronic Health

LBA10500 Background: Modifications in childhood cancer treatments in recent decades have contributed to reductions in late mortality among 5-year survivors. We used the recently expanded CCSS cohort to investigate whether these changes have also reduced the incidence of chronic disease. Methods: We evaluated the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, CTCAE grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999. We calculated the 15-year cumulative incidence of chronic health conditions by decade of cancer diagnosis and compared risk across decades using Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 23,601 survivors, median age 28 years (range 5-63), 21 years from diagnosis (5-43), the 15-year cumulative incidence of grade 3-5 conditions decreased from 12.7% in survivors diagnosed in the 1970s to 10.1% and 8.8% in those diagnosed in the 1980s and 1990s (per 10 years, HR 0.84 [95% CI = 0.80-0.89]). The association with diagnosis decade was attenuated (HR 0.92 [0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk. Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR 0.57 [0.46-0.70]), Hodgkin lymphoma (HR 0.75 [0.65-0.85]), astrocytoma (HR 0.77 [0.64-0.92]), non-Hodgkin lymphoma (HR 0.79 [0.63-0.99]), and acute lymphoblastic leukemia (HR 0.86 [0.76-0.98]). Decreases were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% v. 1990s:1.6%; HR 0.66 [0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% v. 1990s: 1.6%; HR 0.85 [0.76-0.96]). Significant reductions were also found for gastrointestinal (HR 0.80 [0.66-0.97]) and neurological conditions (HR 0.77 [0.65-0.91]), but not cardiac or pulmonary conditions. Conclusions: Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but have also reduced the incidence of serious chronic morbidity in this population.

Genetic Variation in the Leptin Receptor Gene and Obesity in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study

2004 ◽  
Vol 22 (17) ◽  
pp. 3558-3562 ◽  
Author(s):  
Julie A. Ross ◽  
Kevin C. Oeffinger ◽  
Stella M. Davies ◽  
Ann C. Mertens ◽  
Erica K. Langer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Leptin Receptor ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Childhood All ◽  
Female Survivors ◽  
Cranial Radiation ◽  
Childhood Cancer Survivor Study

Purpose Overweight (body mass index [BMI] 25 to 29 kg/m2) and obesity (BMI ≥ 30 kg/m2) frequently follow treatment for childhood acute lymphoblastic leukemia (ALL). Recent studies suggest that risk is most apparent in females treated with cranial radiation at a younger age. Because radiation at a young age may affect the hypothalamus causing leptin receptor insensitivity, we hypothesized that a polymorphism in the leptin receptor (LEPR) gene, Gln223Arg, might influence susceptibility to obesity in survivors of childhood ALL. Patients and Methods We genotyped 600 non-Hispanic white adult ALL survivors enrolled onto the Childhood Cancer Survivor Study. BMI was compared between those with two copies of the Arg allele to those who had at least one copy of the Gln allele. Results Female survivors with BMI ≥ 25 kg/m2 were more likely Arg homozygous than those with BMI less than 25 kg/m2 (24% v 12%; P = .007). This difference was not observed in males. Moreover, among females treated with ≥ 20 Gy cranial radiation, Arg/Arg individuals had six times higher odds of having BMI ≥ 25 kg/m2 (95% CI, 2.1 to 22.0) than those with a Gln allele (P = .04 for interaction). Conclusion LEPR polymorphism may influence obesity in female survivors of childhood ALL, particularly those exposed to cranial radiation. Because obesity is associated with increased morbidity and mortality in later life, identification of children at high risk might allow for early targeted interventions.

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