Neuromuscular Impairments in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: Associations with Physical Performance and Chemotherapy Doses

Background: Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. In this study, the authors examined associations between neuromuscular impairments and physical function and between neuromuscular impairments and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL.

Methods: ALL survivors >10 years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments, and physical performance.

Results: Among 415 survivors (median age, 35 years; age range, 21-52 years), balance, mobility, and 6-minute walk (6MW) distances were 1.3 standard deviations below age-specific and sex-specific values in 15.4%, 3.6%, and 46.5% of participants, respectively. Impairments included absent Achilles tendon reflexes (39.5%), active dorsiflexion range of motion (ROM) <5 degrees (33.5%), and impaired knee extension strength (30.1%). In adjusted models (including cranial radiation), survivors who received cumulative intrathecal methotrexate doses ≥215 mg/m(2) were 3.4 times more likely (95% confidence interval, 1.2-9.8 times more likely) to have impaired ROM than survivors who received no intrathecal methotrexate, and survivors who received cumulative vincristine doses ≥39 mg/m(2) were 1.5 times more likely (95% CI, 1.0-2.5 times more likely) to have impaired ROM than survivors who received lower cumulative doses of vincristine. Higher intrathecal methotrexate doses were associated with reduced knee extension strength and 6MW distances.

Conclusions: Neuromuscular impairments were prevalent in childhood ALL survivors and interfered with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate were associated with long-term neuromuscular impairments, which have implications on future function as these survivors age.