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 urinary 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.
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References
Richards S, Pui CH, Gayon P, Childhood Acute Lymphoblastic Leukemia Collaborative Group (CALLCG). Systematic review and meta-analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013;60:185–95.
Vagace JM, de la Maya MD, Caceres-Marzal C, et al. Central nervous system chemotoxicity during treatment of pediatric acute lymphoblastic leukemia/lymphoma. Crit Rev Oncol Hematol. 2012;84:274–86.
Goldsby RE, Liu Q, Nathan PC, et al. Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2010;28:324–31.
Morales NA, Romano MA, Michael Cummings K, et al. Accuracy of self-reported tobacco use in newly diagnosed cancer patients. Cancer Causes Control. 2013;24:1223–30.
Jacobson GP, Newman CW. The development of the Dizziness Handicap Inventory. Arch Otolaryngol Head Neck Surg. 1990;116:424–7.
Cella D, Davis K, Breitbart W, Curt G, Fatigue Coalition. Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J Clin Oncol. 2001;19:3385–91.
Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer. 1999;85:1186–96.
Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders. Cephalagia. 2004;24 suppl 1:1–160.
Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) questionnaire to assess headache-related disability. Neurology. 2001;56(6 Suppl 1):S20–8.
Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034–9.
Proposal for revised classification of epilepsies and epileptic syndromes. Commission on classification and terminology of the International League Against Epilepsy. Epilepsia. 1989;304:389–99.
Scott-Lennox J, Bryant-Comstock L, Lennox R, Baker GA. Reliability, validity and responsiveness of a revised scoring system for the Liverpool Seizure Severity Scale. Epilepsy Res. 2001;44:53–63.
Dyck PJ, Sherman WR, Hallcher LM, et al. Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry. Ann Neurol. 1980;8:590–6.
Roese I, Kohlmann T, Raspe H. Measuring functional capacity in backache patients in rehabilitation: a comparison of standardized questionnaires. Rehabilitation (Stuttg). 1996;35:103–8.
Krull KR, Khan RB, Ness KK, et al. Symptoms of attention-deficit/hyperactivity disorder in long-term survivors of childhood leukemia. Pediatr Blood Cancer. 2011;57:1191–6.
Wolraich ML, Lambert W, Doffing MA, et al. Psychometric properties of the Vanderbilt ADHD diagnostic parent rating scale in a referred population. J Pediatr Psychol. 2003;28:559–67.
Schmitz-Hübsch T, du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66:1717–20.
McHorney CA, Ware Jr JE, Raczek AE. The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care. 1993;31:247–63.
Besson PS, Labbe EE. Use of the modified mini-mental state examination with children. J Child Neurol. 1997;12:455–60.
Kelvin EA, Hesdorffer DC, Bagiella E, et al. Prevalence of self-reported epilepsy in a multiracial and multiethnic community in New York City. Epilepsy Res. 2007;77:141–50.
Reddick WE, Shan ZY, Glass JO, et al. Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer. 2006;106:941–9.
Wöber-Bingöl C. Epidemiology of migraine and headache in children and adolescents. Curr Pain Headache Rep. 2013. doi:10.1007/s11916-013-0341-z.
Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646–57.
Anttila P. Tension-type headache in childhood and adolescence. Lancet Neurol. 2006;5:268–74.
Lipton RB, Manack A, Ricci JA, et al. Prevalence and burden of chronic migraine in adolescents: results of the chronic daily headache in adolescents study (C-dAS). Headache. 2011;51:693–706.
Mulrooney DA, Ness KK, Neglia JP, et al. Fatigue and sleep disturbance in adult survivors of childhood cancer: a report from the childhood cancer survivor study (CCSS). Sleep. 2008;31:271–81.
Lamers F, Hickie I, Merikangas KR. Prevalence and correlates of prolonged fatigue in a U.S. sample of adolescents. Am J Psychiatry. 2013;170:502–10.
Ramchandren S, Leonard M, Mody RJ, et al. Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. J Peripher Nerv Syst. 2009;14:184–9.
Janssens KA, Rosmalen JG, Ormel J, et al. Pubertal status predicts back pain, overtiredness, and dizziness in American and Dutch adolescents. Pediatrics. 2011;128:553–9.
Bowers DC, Griffith T, Gargan L, et al. Back pain among long-term survivors of childhood leukemia. J Pediatr Hematol Oncol. 2012;34:624–9.
Funding
Supported by Cancer Center Support Grant CA21765 from the National Cancer Institute, and by the American Lebanese Syrian Associated Charities.
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All authors have no financial relationships relevant to this article to disclose.
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There are no financial disclosures, conflicts of interest, and/or acknowledgements for the authors in regards to this manuscript.
Informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients/parents for being included in the study.
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Khan, R.B., Hudson, M.M., Ledet, D.S. et al. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study. J Cancer Surviv 8, 688–696 (2014). https://doi.org/10.1007/s11764-014-0375-1
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DOI: https://doi.org/10.1007/s11764-014-0375-1