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.

Modifiable Risk Factors for Neurocognitive and Psychosocial Problems After Hodgkin Lymphoma

Blood ◽  
2021 ◽  
Author(s):  
AnnaLynn M Williams ◽  
Sedigheh Mirzaei Salehabadi ◽  
Mengqi Xing ◽  
Nicholas Steve Phillips ◽  
Matthew Ehrhardt ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hodgkin Lymphoma ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Cross Sectional ◽  
Chronic Health ◽  
Modifiable Factors ◽  
Task Efficiency

Long-term survivors of childhood Hodgkin lymphoma (HL) experience high burden of chronic health morbidities. Correlates of neurocognitive and psychosocial morbidity have not been well established. 1,760 survivors of HL (mean[SD] age 37.5[6.0] years, time since diagnosis 23.6[4.7] years, 52.1% female) and 3,180 siblings (age 33.2[8.5] years, 54.5% female) completed cross-sectional surveys assessing neurocognitive function, emotional distress, quality of life, social attainment, smoking, and physical activity. Treatment exposures were abstracted from medical records. Chronic health conditions were graded according to NCI CTCAE v4.3 (1=mild, 2=moderate, 3=severe/disabling, 4=life-threatening). Multivariable analyses, adjusted for age, sex, and race, estimated relative risk (RR) of impairment in survivors vs. siblings and, among survivors, risk of impairment associated with demographic, clinical, treatment factors and grade 2+ chronic health conditions. Compared with siblings, survivors had significant higher risk (p's<0.05) of neurocognitive impairment (e.g. memory 8.1% vs. 5.7%), anxiety (7.0%%vs. 5.4%),depression (9.1% vs. 7%), unemployment (9.6% vs. 4.4%), and impaired physical/mental quality of life (e.g. physical function 11.2% vs. 3.0%). Smoking was associated with higher risk of impairment in task efficiency (RR=1.56[1.02-2.39]), emotional regulation (RR=1.84[1.35-2.49]), anxiety (RR=2.43[1.51-3.93]), and depression (RR=2.73[1.85-4.04]). Meeting CDC exercise guidelines was associated with lower risk of impairment in task efficiency (RR=0.70[0.52-0.95]), organization (RR=0.60[0.45-0.80]), depression (RR=0.66[0.48-0.92]), and multiple quality of life domains. Cardiovascular and neurologic conditions were associated with impairment in nearly all domains. Survivors of HL are at elevated risk for neurocognitive and psychosocial impairment, and risk is associated with modifiable factors that provide targets for interventions to improve long-term functional outcomes.

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.

Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11563-11563
Author(s):  
Caroline Hesko ◽  
Wei Liu ◽  
Deokumar Srivastava ◽  
Tara M. Brinkman ◽  
Lisa Diller ◽  
...  
Keyword(s):  
At Risk ◽  
Hearing Loss ◽  
Emotional Regulation ◽  
Adult Survivors ◽  
Neurocognitive Impairment ◽  
Age At Diagnosis ◽  
Neurocognitive Outcomes ◽  
Childhood Cancer Survivor Study ◽  
Task Efficiency ◽  
Long Term Survivors

11563 Background: Long-term survivors of neuroblastoma may be at risk for neurocognitive impairment due to young age at diagnosis and intensive multimodal therapies. Methods: 837 survivors of neuroblastoma (57% female; median [range] age 25 [17-58] years, age at diagnosis 1 [0-21] years) and 728 siblings (56% female; age 32[16-43] years) self-reported neurocognitive problems using a neurocognitive questionnaire. Impairment was defined as scores ≥90th percentile of siblings in emotional regulation (ER), organization, task efficiency (TE), and memory. Multivariable log-binomial models evaluated associations with treatment exposures, era and chronic conditions (Grade 2-4 CTCAE v5) adjusting for sex, age, and race. Analyses were stratified by age at diagnosis (≤1 and > 1 year) as proxy for risk group. Results: Rates of impairment were 19.7% (ER), 25.3% organization, 21.9% TE and 19.4% for memory. Survivors had 50% higher risk of impaired TE (≤1 year relative risk [RR] 1.48, 95% confidence interval [CI] 1.08-2.03; > 1 year: RR 1.58, CI 1.22-2.06) and ER (≤1 year RR 1.51, CI 1.07-2.12; > 1 year RR 1.44, CI 1.06-1.95) versussiblings. Among survivors ≤1 year at diagnosis, treatment with platinum (RR 1.74, CI 1.01-2.97), hearing loss (RR 1.95, CI 1.26-3.00), cardiovascular (RR 1.83, CI 1.15-2.89) and neurologic (RR 2.00, CI 1.32-3.03) conditions were associated with higher risk of impaired TE. Female sex (RR = 1.54, CI, 1.02-2.33), cardiovascular (RR 1.71, CI 1.08-2.70) and respiratory (RR 1.99, CI 1.14-3.49) conditions were associated with higher risk of impaired ER. Among survivors > 1 year at diagnosis those treated in 1970-79 vs. 1990-99 had 80% higher risk of impaired ER (RR 1.77, CI 1.02-3.06). Hearing loss (RR 1.56 (1.09-2.24), respiratory (RR 2.35, CI 1.60-3.45) and cardiovascular (RR 1.74, CI 1.12-2.69) conditions were associated with higher risk of impaired TE. Conclusions: Adult survivors of neuroblastoma are at-risk for neurocognitive impairment. Differences associated with age at diagnosis, chronic disease and treatment exposures may inform risk-stratified inventions to improve neurocognitive outcomes. Reduced risk in later eras may reflect improved supportive care and knowledge of late effects.

scholarly journals Late Health Outcomes After Contemporary Lymphome Malin de Burkitt Therapy for Mature B-Cell Non-Hodgkin Lymphoma: A Report From the Childhood Cancer Survivor Study

2019 ◽  
Vol 37 (28) ◽  
pp. 2556-2570 ◽  
Author(s):  
Matthew J. Ehrhardt ◽  
Yan Chen ◽  
John T. Sandlund ◽  
Elizabeth C. Bluhm ◽  
Robert J. Hayashi ◽  
...  
Keyword(s):  
Health Status ◽  
Health Outcomes ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Socioeconomic Outcomes ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Childhood Cancer Survivor Study

PURPOSE The widely used, risk-based Lymphome Malin de Burkitt (LMB) chemotherapy regimen has improved survival rates for children with mature B-cell non-Hodgkin lymphoma (NHL); however, associated late effects remain understudied. We assessed late health outcomes after LMB treatment in the Childhood Cancer Survivor Study. PATIENTS AND METHODS Multivariable regression models compared chronic health conditions, health status, and socioeconomic and neurocognitive outcomes between survivors of NHL treated with the LMB regimen (n = 126), survivors of NHL treated with non-LMB regimens (n = 444), and siblings (n = 1,029). RESULTS LMB survivors were a median age of 10.2 years (range, 2.5 to 20.5 years) at diagnosis and 24.0 years (range, 10.3 to 35.3 years) at evaluation. Compared with siblings, LMB survivors were at increased risk for adverse health outcomes. However, survivors of NHL treated with LMB and non-LMB regimens did not differ with regard to risk of having any chronic health conditions, impaired health status, neurocognitive deficits, or poorer socioeconomic outcomes. Increased risk for the following specific neurologic conditions was observed in LMB survivors compared with non-LMB survivors: epilepsy (relative risk [RR], 15.2; 95% CI, 3.1 to 73.4); balance problems (RR, 8.9; 95% CI, 2.3 to 34.8); tremors (RR, 7.5; 95% CI, 1.9 to 29.9); weakness in legs (RR, 8.1; 95% CI, 2.5 to 26.4); severe headaches (RR, 3.2; 95% CI, 1.6 to 6.3); and prolonged arm, leg, or back pain (RR, 4.0; 95% CI, 2.2 to 7.1). The survivors from the group C LMB risk group (n = 50) were at the highest risk for these conditions; however, except for worse functional status (odds ratio, 2.7; 95% CI, 1.2 to 5.8), they were not at increased risk for other adverse health status or socioeconomic outcomes compared with non-LMB survivors. CONCLUSION Survivors treated with LMB and non-LMB regimens are largely comparable in late health outcomes except for excess neurotoxicity among LMB survivors. These data inform treatment efforts seeking to optimize disease control while minimizing toxicity.

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.

High Prevalence of Chronic Health Conditions in Survivors of Hodgkin Lymphoma Treated during Adulthood.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4390-4390
Author(s):  
Matthew J. Matasar ◽  
John N. Butos ◽  
Elyn R. Riedel ◽  
Jennifer S. Ford ◽  
David M. Weinstock ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Health Condition ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Second Primary ◽  
Adult Onset ◽  
Chronic Health ◽  
High Prevalence ◽  
Grade 3 ◽  
Second Primary Malignancies

Abstract Background: An increased risk of morbidity, including second primary malignancies and cardiovascular disease, has been reported in survivors of Hodgkin lymphoma (HL) diagnosed during adulthood. However, in contrast to our understanding of the late effects of treatment of children with HL, the global burden of chronic morbidity among long-term survivors of adult-onset HL is poorly characterized. Methods: We conducted a survey-based cohort study of patients treated as adults with protocol-based first-line therapy for HL at our center from 1975 to 2000. The protocols included 6 combined modality trials (CMT) of chemotherapy (CT) + radiation therapy (RT), with the exception of a single CT-only arm in 1 trial. Chronic health conditions were assigned severity scores based on a modification of the Common Terminology Criteria for Adverse Events, version 3 (grades 1 through 4, ranging from mild to life-threatening or disabling). Results: Of 707 patients for whom follow-up was available, 517 were alive. Median survival was 29 years. Survey data were available from 169 patients, with a median time from last treatment to interview date of 21 years. Of responders, median age at interview was 48 years (range, 25–88) and median age at treatment was 29 years (range, 16–66). Fifty percent were women, and 96% were white, non-Hispanic. Self-reported chronic health conditions were very common in our cohort: 94% of respondents reported any chronic health condition, and 60% described chronic health conditions that were grades 3 or 4 in severity (Table 1). Frequently reported conditions included cardiovascular, musculoskeletal, endocrine, and psychiatric disorders. Sixty percent of patients reported grade ≥1 cardiovascular dysfunction (20% ≥grade 3), 40% grade ≥1 musculoskeletal (7% ≥grade 3), 71% ≥grade 1 endocrine (17% ≥grade 3), and 23% ≥grade 1 psychiatric (21% ≥grade 3). Second primary malignancies were reported by 23%, and infectious conditions by 34%. Additional data collection on surviving and deceased patients is ongoing. Conclusions: These results document the high prevalence of chronic illness among survivors of HL treated as adults. Evidence-based guidelines built upon such data are needed to aid clinicians in the management of the late morbidities associated with HL treatment. Table 1. Chronic health conditions among adult-onset Hodgkin lymphoma survivors, according to severity score. Health Condition Frequency (%) Conditions by grade No condition 10 (6%) Grade 1 17 (10%) Grade 2 41 (24%) Grade 3 67 (40%) Grade 4 34 (20%) Any condition Grades 1–4 159 (94%) Grade 3 or 4 101 (60%) Multiple health conditions ≥Grade 1 ≥2 conditions 142 (84%) ≥3 conditions 120 (71%) ≥Grade 2 ≥2 conditions 111 (66%) ≥3 conditions 72 (43%) ≥Grade 3 ≥2 conditions 50 (30%) ≥3 conditions 19 (11%)

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