Obesity associated with neurocognitive impairment among survivors of childhood leukemia

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Disclosures:
Inaba reports grants or research support from Amgen, Incyte and Servier; advisory fees from Jazz Pharmaceuticals and Servier; and Chugai Pharmaceutical fees. Krull reports grants from the National Institute of Mental Health and NCI. See the study for all relevant financial disclosures from authors.

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Overweight and obesity were found to be significantly associated with neurocognitive impairment during long-term follow-up of subjects receiving chemotherapy for acute childhood lymphoblastic leukemia, according to a study published in Cancer.

“We had previously learned that patients with ALL gain weight during therapy, especially during induction, and this persists even after completion of therapy,” Hiroto Inaba, MD, PhD, a faculty member in the oncology department at St. Jude Children’s Research Hospital, Healio said. “Obesity has been reported to affect neurocognitive function in the general population. More like a group [led by co-author Kevin R. Krull, PhD,] showed that [patients with ALL] develop problems with neurocognitive function. Therefore, we thought that the obesity in ALL survivors exacerbates poorer neurocognitive function. “

Data is derived from Iijima M, et al. Cancer. 2021; doi: 10.1002 / cncr.33624.

The analysis included 210 survivors of ALL in children treated according to the St. Jude Total XV protocol – a chemotherapy-based regimen that does not include cranial radiation – who were at least 8 years old (median age at diagnosis, 5 years; range; 3.2-8.7; 51.4% male; 73.8% Caucasian) and at least 5 years after their diagnosis. Of these, 120 were healthy / underweight, 42 were overweight and 48 were obese.

Hiroto Inaba

In a cross-sectional analysis, Inaba and colleagues evaluated the association between neurocognitive function, using age-adjusted Z-score and BMI-category and Z-score. Due to the fluctuating nature of BMI, researchers also conducted a longitudinal analysis in which they considered overweight or obesity as an exposure, expressed in area under the curve.

Survivors had a median BMI Z-score at diagnosis of 0.17, which increased to 0.54 at the end of induction and to 0.74 at the neurocognitive assessment.

Results of the cross-sectional analysis showed that overweight or obese survivors at the time of neurocognitive assessment scored significantly lower than healthy survivors / underweight survivors in terms of executive functions, including cognitive flexibility, planning, verbal fluency, working memory, and spatial construction; attention, including attention span and risk-taking; and by processing speed, including visual motor coordination, visual speed and motor speed (all P <.05).

In addition, the longitudinal analysis – evaluating induction, consolidation, early maintenance and late maintenance as four separate treatment periods – showed a greater AUC for overweight / obesity during induction therapy, which was associated with poorer cognitive flexibility (P = .01) and lower motor speed . (P = 0.02), which was maintained throughout treatment. A higher overweight / obese AUC also negatively impacted attention span during early and late maintenance and consolidation therapy (all p <.05).

Given these findings and the fact that obesity starts during induction therapy, early intervention should be considered, Inaba said.

“We should actively consider taking early action to reduce or prevent weight gain [patients with ALL] and ultimately worse neurocognitive function, ”he said.

Kevin R. Krull

Krull, professor of cancer survival in the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, added that inflammation and poor sleep quality were previously associated with neurocognitive problems in ALL survivors, and he entered the study with the belief that obesity may be partly responsible for these difficulties.

“We have preliminary evidence that if parents focus on a healthy lifestyle at home, it can not only improve diet and physical activity, but also reduce sedentary behavior and screen time and improve sleep quality,” Krull told Healio.

The researchers noted that the study may be limited because they did not examine obesity-related behaviors, such as physical activity and diet, which can be explored in further research.

“We recently conducted such interventions targeting healthy home environments, and we are currently planning a larger study,” said Krull.

For more information:

Hiroto Inaba, MD, PhD, can be reached at Department of Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, 260 Mail Stop, Memphis, TN 38105-2794; email: hiroto.inaba@stjude.org.

Kevin R. Krull, PhD, can be reached at Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105-2794; email: kevin.krull@stjude.org.

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