Despite major advances in the treatment of acute lymphoblastic leukemia (ALL), adult survivors face long-term health consequences. A recent review published in Frontiers in Oncology examined the long-term sequelae on adult survivors after chemotherapy for pediatric ALL and underlying mechanisms.

Cure rates of ALL exceed 90% thanks to highly effective new treatments. The current analysis describes the long-term adverse events in children with ALL according to the Children’s Oncology Group (COG) long-term follow-up guidelines for practitioners (LTFU). The authors also used data from the Childhood Cancer Survivor Study (CCSS), which included cancer survivors diagnosed between 1970 and 1999.

Pediatric ALL patients are at higher risk than the general population of developing secondary malignant neoplasms (SMNs). However, SMNs are rare. TP53 and POT1 variants may be linked to the development of SMNs and warrant further study in this population.

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Cardiotoxicity related to anthracycline use is another long-term adverse event for these patients. Certain biomarkers may be used to develop individualized therapy.

Some long-term effects are modifiable, such as bone health and obesity. Corticosteroid use increases the risk of fractures, with 65% of pediatric patients with ALL reporting fractures. Methotrexate, asparaginase, anthracyclines, and vincristine can affect patients’ long-term bone health as well. Bone assessment and calcium and vitamin D supplementation are recommended.

Childhood survivors of ALL have a higher prevalence of obesity, even in patients who have been off treatment for a decade. The mechanism that increases risk isn’t fully understood, but chemotherapy seems to be an independent risk factor.

Chemotherapy and radiation in pediatric patients with ALL can harm their fertility. Addressing this requires further research into fertility preservation methods. Additionally, vincristine is a common component of ALL treatment, but it is a neurotoxic agent and can lead to long-term peripheral neuropathy.

Peripheral neuropathy, ocular effects, fertility, neurocognitive impairment, and liver function impairment have limited long-term research available.

Genetic testing and biomarkers may open new avenues to better understanding and preventing or minimizing long-term effects of treatment. Advances in targeted therapies may also lead to treatments that have fewer long-term adverse events.


Al-Mahayri ZN, AlAhmad MM, Ali BR. Long-term effects of pediatric acute lymphoblastic leukemia chemotherapy: can recent findings inform old strategies? Front Oncol. 2021;11:710163. doi:10.3389/fonc.2021.710163