Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study

Abstract

Purpose Childhood acute lymphoblastic leukemia (ALL) is treated with potentially neurotoxic drugs and neurologic complications in long-term survivors are inadequately studied. This study investigated neurologic morbidity and its effect on quality of life in long-term survivors of childhood ALL. Methods Prospective, single institution, cross-sectional, institutional review board-approved study of long-term ALL survivors. Participants were recruited from institutional clinics. Participants answered an investigator-administered questionnaire followed by evaluation by a neurologist. Quality of life (QOL) was also assessed. Results Of the 162 participants recruited over a 3-year period, 83.3 % reported at least one neurologic symptom of interest, 16.7 % had single symptom, 11.1 % had two symptoms, and 55.6 % had three or more symptoms. Symptoms were mild and disability was low in the majority of participants with neurologic symptoms. Median age at ALL diagnosis was 3.9 years (0.4–18.6), median age at study enrollment was 15.7 years (6.9–28.9), and median time from completion of ALL therapy was 7.4 years (1.9–20.3). On multivariable analyses, female sex correlated with presence of dizziness, urinary incontinence, constipation, and neuropathy; use of≥10 doses of triple intrathecal chemotherapy correlated with uri-nary incontinence, back pain, and neuropathy; cranial radiation with ataxia; history of ALL relapse with fatigue; and CNS leukemia at diagnosis with seizures. Decline in mental QOL was associated with migraine and tension type headaches, while physical QOL was impaired by presence of dizziness and falls. Overall, good QOL and physical function was maintained by a majority of participants. Conclusions Neurologic symptoms were present in 83 % long-term ALL survivors. Symptoms related morbidity and QOL impairment is low in majority of survivors. Female sex, ≥10 doses of intrathecal chemotherapy, and history of ALL relapse predispose to impaired QOL. Implications for Cancer Survivors This study will educate survivors and their care providers regarding cancer or treatment-related neurologic symptoms and morbidity. This study will help them understand factors contributing to impaired QOL when present.

Vincristine‐induced peripheral neuropathy in survivors of childhood acute lymphoblastic leukaemia

“…Ramchandren et al . did not observe any impact on the quality of life of their cohort of ALL survivors despite evidence of electrophysiological neuropathy, while another study found that physical quality of life was not impaired in patients with clinical neuropathy . This is in contrast to our study in which ALL survivors with VIPN reported lower quality of life scores in the physical and social domains compared with those without VIPN.…”

“…Neurophysiological studies have demonstrated increased distal latencies, decreased amplitudes of compound muscle action potentials and sensory nerve action potentials with little or no change in nerve conduction velocities in peripheral nerves following exposure to vincristine . Despite extensive studies on the neurotoxic effects of vincristine, there is still paucity of data on its long‐term effects in ALL survivors and its impact on function and quality of life in affected individuals . In addition, the evaluation and reporting methods have varied between studies, precluding any direct comparisons and conclusions.…”

“…11 Despite extensive studies on the neurotoxic effects of vincristine, there is still paucity of data on its long-term effects in ALL survivors and its impact on function and quality of life in affected individuals. [12][13][14][15] In addition, the evaluation and reporting methods have varied between studies, precluding any direct comparisons and conclusions.…”

A systematic review of self‐reported pain in childhood cancer survivors

“…The reported findings indicate that pain is a significant clinical problem for specific subgroups of childhood cancer survivors, such as bone cancer, CNS tumours, sarcoma, RMS, retinoblastoma and ALL survivors, for whom back pain was reported to be a frequent symptom . Previous studies have shown that back pain and neuropathy are associated with the number of times intrathecal chemotherapy is administered …”

Effect of Temporal Changes in Therapeutic Exposure on Self-reported Health Status in Childhood Cancer Survivors

“…Among ALL survivors, this may be related to increased use of intrathecal therapy to treat CNS disease in the more recent era. Data indicate that back pain is a frequent complaint of adult survivors of ALL (42), and that back pain and neuropathy are associated with the number of intrathecal chemotherapy administrations (43). In osteosarcoma survivors, this may be due to increases in numbers of younger patients eligible for limb-sparing related to availability of expandable prostheses in the 1990s, many of whom required multiple surgeries to manage orthopedic complications.…”