Providing Primary Care for Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia
Primary care physicians will be providing longitudinal health care for long-term survivors of childhood acute lymphoblastic leukemia (ALL) with increasing frequency. Late effects (sequelae) secondary to treatment with radiation or chemotherapeutic agents are frequent and may be serious. Depending on treatment exposures, this at-risk population may experience life-threatening late effects, such as cirrhosis secondary to hepatitis C or late-onset anthracycline-induced cardiomyopathy, or life-changing late effects, such as cognitive dysfunction. Many survivors of childhood ALL will develop problems such as obesity and osteopenia at a young age, which will significantly affect their risk for serious health outcomes as they grow older.
The goal of our review is to assist primary care physicians in providing longitudinal health care for long-term survivors of childhood ALL. We also highlight areas needing further investigation, including the prevalence of different late effects, determination of risk factors associated with a late effect, a better understanding of the potential impact of late effects on the premature development of common adult health problems, and the value and timing of different tests for screening asymptomatic survivors.
Urologic late effects
Cyclophosphamide is a long-recognized cause of hemorrhagic cystitis and a well-established bladder carcinogen. In a retrospective review150 of 314 children with ALL who were treated with cyclophosphamide between 1963 and 1973, 8% developed hemorrhagic cystitis. The frequency of diagnosis was not related to age or sex, but African American children were at higher risk. Cyclophosphamide-induced hemorrhagic cystitis generally presents during therapy, with children complaining of gross hematuria or irritative voiding complaints.151 Concurrent treatment with oral sodium 2-mercapatoethanesulfonate appears to markedly decrease the incidence of cyclophosphamide-induced hemorrhagic cystitis.152 In a nested case-control study of survivors of non–Hodgkin’s lymphoma, Travis and colleagues153 reported that there was a 2.4-fold increased risk of bladder cancer in patients treated with cumulative dosages of cyclophosphamide lower than 20 g. Because of the risk of chronic hemorrhagic cystitis and bladder cancer, ALL survivors treated with cyclophosphamide should have periodic screening urinalysis, and their review of systems should include voiding problems.
Alopecia
Alopecia is a bothersome late effect secondary to treatment with 24 Gy CRT for which there are no available treatments. In a retrospective study of 273 ALL survivors treated with CRT, 10% had alopecia.154
Acknowledgement
Dr Oeffinger received partial support for this work through the American Academy of Family Physicians Foundation Advanced Research Training Grant and the Robert Wood Johnson Foundation Generalist Physician Faculty Scholars Program.
We would like to thank Drs George Buchanan, Melissa Hudson, and Neyssa Marina for their critical review of this manuscript and Ms Laura Snell and Dr James Tysinger for their editing assistance.
