The population of survivors of childhood leukemia who reach adulthood is growing due to improved therapy. However, survivors are at risk of long-term complications. Comprehensive follow-up programs play a key role in childhood leukemia survivor care. The major determinant of long-term complications is the therapeutic burden accumulated over time. Relapse chemotherapy, central nervous system irradiation, hematopoietic stem cell transplantation, and total body irradiation are associated with greater risk of long-term complications. Other parameters include clinical characteristics such as age and sex as well as environmental, genetic, and socioeconomic factors, which can help stratify the risk of long-term complications and organize follow-up program. Early diagnosis improves the management of several late complications such as anthracycline-related cardiomyopathy, secondary cancers, metabolic syndrome, development defects, and infertility. Total body irradiation is the treatment associated with worse long-term toxicity profile with a wide range of complications. Patients treated with chemotherapy alone are at a lower risk of long-term complications, although the optimal long-term follow-up remains unclear. Novel immunotherapies and targeted therapy are generally associated with a better short-term safety profile but still require careful long-term toxicity monitoring. Advances in understanding genetic susceptibility to long-term complications could enable tailored therapeutic strategies for leukemia treatment and optimized follow-up programs.
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