Survivors of the most common childhood cancer, acute lymphoblastic leukemia (ALL), need long-term monitoring for obesity and other ongoing health consequences of their disease and treatment.

“The etiology of obesity among ALL survivors is not fully understood, but the primary tumor, hypothalamic-pituitary axis damage from cranial radiation or chemotherapy, lifestyle modifications, and genetics all may play a role,” said Kerry K. McGowan, M.D., a pediatric hematologist/oncologist at Norton Children’s Cancer Institute, affiliated with the UofL School of Medicine.

Over the last half-century, five-year survival for ALL has risen to more than 80%. Treatment involves high doses of chemotherapy, radiation therapy, or a combination of the two, frequently resulting in late effects.

“Helping these children survive ALL is only the first step. We need to monitor them for late effects, offering lifestyle modifications and medical interventions, as needed,” Dr. McGowan said.

Cancer survivors are enrolled in Norton Children’s Cancer Institute’s survivorship program two to five years after treatment. The program follows Children’s Oncology Group survivorship guidelines and provides necessary follow-up care. Survivorship rates for children are greater than 80%, but more than half of survivors will have chronic issues.

When patients are at an appropriate age, off therapy and emotionally ready, they transition to the Norton Cancer Institute Survivorship Program.

Norton Children’s Cancer Institute physicians continue to research various late effects and interventional options as part of the Children’s Oncology Group’s long-term studies.

Inactivity and weight gain during treatment

Cranial radiation and glucocorticoids are associated with an increase in body mass index (BMI), but even children who did not receive these therapies are at higher risk of treatment-related increases in BMI.

The period with the most weight gain is typically during the first year of treatment, but weight gain continues after the end of treatment.

During treatment, children with ALL tend to become less physically active. This may result from hospitalization. Children also may experience diminished exercise capacity and a diminished interest in exercise. In addition, overprotective caregivers may limit physical activity. Pathophysiological changes in the cardiorespiratory system, growth hormone insufficiency, steroid-related myopathy and vincristine-related neuropathy also may play a role.

ALL survivorship and cardiovascular disease

Treatment-related obesity and metabolic syndrome in adult ALL survivors are risk factors for cardiovascular disease. Almost 75% of ALL survivors have a chronic health condition affecting their cardiovascular morbidity and mortality.

Dietary counseling and individualized exercise regimens can help mitigate the risk of obesity and metabolic syndrome, especially when started during treatment or early in survivorship. Medical intervention may be indicated, however, to mitigate risk factors of cardiovascular disease, according to Dr. McGowan.

Osteopenia and osteoporosis risk

In addition to weight gain, height typically is compromised in ALL survivors, whether or not they received radiation, especially among those diagnosed before age 13 or with increased chemotherapy intensity.

Because ALL begins in the bone marrow and occurs during a time in life when peak bone mass normally is achieved, it also can result in osteopenia and osteoporosis and contribute to fractures in bones and vertebrae. Use of steroids, which is a mainstay in treatment, can cause direct inhibitory effects on osteoblast activity and reduction in intestinal absorption of calcium, which also is a contributory factor.

Other described late effects are musculoskeletal pain, disturbed gait, kyphosis, lordosis and growth failure.