Childhood ALL Survivors Struggle with Obesity and Long-Term Fitness Deficits

In the past few decades, treatment of childhood acute lymphoblastic leukemia (ALL) has been recognized as one of the true success stories in hematologic malignancies, with five-year survival rates that now exceed 90 percent. Part of the evolution in ALL therapy has included elimination of cranial radiation therapy (CRT) from the treatment plan. Yet, as children with ALL age, they have a higher risk for obesity, poor energy balance, and poor fitness later in life compared with their peers. That risk remains high even if the patient did not undergo CRT, but there are little data on how this subset of ALL survivors fare over the long-term.

Researchers from St. Jude Children’s Research Hospital in Memphis, Tennessee, led by Kirsten Ness, PT, PhD, took a closer look at this issue by focusing on patients from the St. Jude Lifetime Cohort, which is designed to “characterize health outcomes among aging survivors of childhood cancer.”1

Eligible subjects who agreed to participate had an ALL diagnosis from 1980 to 2003 and had to be younger than 18 at the time of diagnosis. They also could not have any congenital neuromusculoskeletal or cardiopulmonary impairments and were not undergoing cancer treatment as adults. An age-, gender-, and race-matched control group was recruited from the patients’ circle of family and friends. The final study population consisted of 365 patients and 365 matched controls.

Dr. Ness and colleagues found that ALL survivors (mean age 28.6 with 21.9 mean years of survival time) who had CRT were shorter, but they were similar in weight to the control group which resulted in them having a higher body mass index (BMI). ALL survivors who had CRT also had a higher BMI compared with patients who did not undergo CRT (TABLE).

However, the researchers wrote, “The half of ALL survivors not exposed to CRT are [also] overweight or obese, increasing their risk for other chronic health conditions, such as diabetes, heart disease, and some types of cancer.” Resting energy expenditure (REE), measured with indirect calorimetry, also came in lowest among survivors exposed to CRT. REE refers to the amount of energy or food calories required for a 24-hour period by the body during resting conditions.

With regard to the links between treatment and fitness, patients with higher cumulative doses of asparaginase (≥120,000 IU/m2) had lower average performance on a sit-and-reach test (p=0.001), as well as less dorsiflexion range of motion (p=0.03) and quadriceps and dorsiflexion strength (p=0.002; p<0.001) compared with those exposed to lower cumulative doses of the drug.

The researchers also reported that cumulative exposure to glucocorticoid steroids was linked to decreased hand strength.

In an interview with ASH Clinical News, Dr. Ness recommended referring patients with these impairments to a physical therapist or other rehabilitation specialist. “I think that physical therapy screening and appropriate intervention during and immediately following treatment is important to address the needs of children with ALL,” Dr. Ness explained. “Physical therapists will work with the child and his or her family to regain function, teach compensatory strategies for recreation and sport participation when an impairment is present, and help children choose activities they can be successful doing.”

In this study, Dr. Ness and colleagues concluded that “clinicians who treat ALL survivors should monitor them for [impaired flexibility, muscle weakness, and poor exercise tolerance] and make appropriate referrals for lifestyle interventions.”

It is important to note that this study had some limitations. Not all eligible subjects from the St Jude Lifetime Cohort opted to take part in the study. If those non-participatory survivors were healthier, then the study’s estimates may be biased away from the null, the researchers explained. Also, some of the lifestyle measures, such as smoking status and diet, were based on self-report and may not be entirely accurate.

When asked whether these childhood ALL survivors could benefit from participating in widely available exercise programs (such as gyms or group classes) as adults, Dr. Ness stressed that “exercise prescription should be tailored to accommodate the specific needs of each survivor so that he or she can be not only safe, but successful, when starting to exercise. All exercise should be tailored to capacity and interests.”

While Dr. Ness’ group did not assess the psychosocial well-being of these patients, other data have shown risks for depression, poor sleep, and poor quality of life among childhood ALL survivors. Dr. Ness concurred that these emotional factors can influence levels of physical activity, so they should be taken into consideration when designing a fitness intervention.

In the near future, her group intends to conduct further studies about the effects of dietary protein intake on lean muscle mass in this patient population. “Several exercise interventions for currently treated patients and for survivors are also in the planning stages,” she added.2


References

  1. Ness KK, DeLany JP, Kaste SC, et al. Energy balance and fitness in adult survivors of childhood acute lymphoblastic leukemia. Blood. 2015 March 26. [Epub ahead of print]
  2. Esbenshade AJ, Friedman DL, Smith WA, et al. Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia. Pediatr Phys Ther. 2014:26:301-7.

 

TABLE. Comparison of Mean Body Composition and Energy Balance Among ALL survivors by CRT Exposure

No CRT (A) CRT (B) Control (C) p values A vs. B p values B vs. C
Females
Mean height 163.9 cm 158 cm 164.2 cm p<0.001 p<0.001
Mean weight 71.1 kg 81.2 kg 74.9 kg p=0.01 p=0.07
Mean BMI 26.4 kg/m2 32.3 kg/m2 27.8 kg/m2 p<0.001 p<0.001
Males
Mean height 176.1 cm 172.9 cm 178.9 cm p=0.003 p<0.001
Mean weight 87.7 kg 87.8 kg  87.3 kg p=0.09 p=0.39
Mean BMI 28.8 kg/m2 28.4 kg/m2 27.2 kg/m2 p=0.62 p=0.12

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