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Long-Term Childhood Hodgkin Lymphoma Survivors Have Increased Risk of Neurocognitive Impairment

January 31, 2022

February 2022

Long-term survivors of childhood Hodgkin lymphoma (HL) are at an increased risk of neurocognitive impairment. Exercise and smoking represent modifiable risk factors for this impairment that may prove useful as treatment targets to improve functional outcomes, according to a study in Blood.

“The findings from this study suggest that survivors of [HL] require life-long regular screening for early detection of chronic health conditions and that healthy lifestyle behaviors need to be strongly encouraged as these survivors appear more vulnerable to neurocognitive and psychosocial sequelae from these events,” said corresponding author Kevin R. Krull, PhD, of St. Jude Children’s Research Hospital in Memphis.

The cross-sectional study included 1,781 adult survivors of HL who were enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS) cohort. The investigators also included 3,196 siblings from the CCSS cohort as a comparator group in the analysis. The mean ages of survivors and siblings at time of inclusion in the analysis were 37.5 years and 33.2 years, respectively. Median time from diagnosis in HL survivors was 23 years.

Researchers conducted cross-sectional surveys that assessed participants’ neurocognitive function (Neurocognitive Questionnaire), emotional distress (Brief Symptom Inventory-18), health-related quality of life (QoL; Medical Outcomes Short Form-36), social attainment (e.g., education, income, employment, and independent living), smoking, and physical activity.

In an analysis adjusted for age, sex, and race/ethnicity, survivors of HL were significantly more likely than siblings to have impairments on several neurocognitive domains, including:

  • organization (relative risk [RR] = 1.32; 95% CI 1.01-1.73)
  • memory (RR=1.72; 95% CI 1.21-2.44)
  • emotional regulation (RR=1.56; 95% CI 1.23-1.99)
  • task efficiency (RR=1.37; 95% CI 1.01-1.85)

 

Survivors of HL who were current and former smokers had the highest risk of impairments in memory, emotional regulation, and task efficiency. Those who met Centers for Disease Control and Prevention (CDC) recommendations for exercise had a lower risk of impairment in task efficiency (RR=0.69; 95% CI 0.51-0.93) and organization (RR=0.59; 95% CI 0.44-0.78). Obesity in survivors was associated with a higher risk of impairments in task efficiency (RR=1.64; 95% CI 1.26-2.13) and memory (RR=1.61; 95% CI 1.04-2.47).

Compared with siblings, survivors of HL had a higher risk of anxiety (RR=1.31; 95% CI 1.01-2.85) and depression (RR=1.33; 95% CI 1.08-1.64). Current smoking in survivors was also associated with an increased risk of anxiety and depression, while those who met CDC recommendations for exercise had a lower risk of depression.

While HL survivors had a higher risk of impairment in all QoL domains compared with siblings, the groups did not differ for pain domains. In HL survivors, modifiable risk factors associated with impairment in eight of the QoL domains included smoking and obesity. In contrast, physical activity was associated with a reduced risk of impairment in each QoL domain.

Grade ≥2 cardiovascular and neurologic conditions were associated with impairment in all four neurocognitive domains, anxiety, and depression, as well as all QoL domains.

Survivors of HL were more likely than siblings to be unemployed (RR=2.02; 95% CI 1.68-2.42) or employed on a part-time basis (RR=1.71; 95% CI 1.31-2.23) and to have a personal income of less than $20,000 (RR=1.80; 95% CI 1.35-2.40). Impairment in task efficiency was also associated with an increased risk of low income (RR=1.42; 95% CI 1.08-1.87) and unemployment (RR=3.41; 95% CI 1.91-6.07). Although memory impairment (RR=1.89; 95% CI 1.02-3.48) and depression (RR=1.87; 95% CI 1.01-3.46) were associated with higher risk of unemployment, anxiety was associated with a lower risk (RR=0.37; 95% CI 0.17-0.81).

According to Dr. Krull, clinicians can follow Children’s Oncology Group guidelines to conduct risk-based screening for various chronic health conditions that are common in survivors of HL and thus target modifiable risk factors to improve long-term outcomes.

“Some conditions, such as hypertension, can be managed very effectively, and doing so may miti­gate some neurocognitive impairments and improve QoL,” he said. “Clinicians can also counsel their patients and survivors to exercise daily and quit smoking.”

Dr. Krull and colleagues concluded that their “data highlight the added burden of poor QoL as well as neurocognitive and emotional distress sequelae to the well-recognized physiologic morbidity and premature mortality in long-term survivors of childhood HL.” Additionally, the research revealed “avenues for future intervention-based research designed to improve these long-term outcomes.” 

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Williams ALM, Salehabadi SM, Xing M, et al. Modifiable risk factors for neurocognitive and psychosocial problems after Hodgkin lymphoma [published online ahead of print, 2021 Dec 3]. Blood. doi: 10.1182/blood.2021013167.

 

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