The implementation of risk-stratified therapy appears to reduce late morbidity and mortality among survivors of pediatric acute lymphoblastic leukemia (ALL), according to research published in the Journal of Clinical Oncology.

Pediatric ALL represents one-fifth of cancers diagnosed in all patients younger than 20 years. While survival rates have increased from 10% to 90% over the past half-century, toxicity from treatment has historically reduced life expectancy. To combat this risk, clinicians introduced risk-stratified treatment, in which highly toxic prophylactic treatments, such as cranial radiation therapy, are foregone unless necessary.

Whether risk-stratified treatment has reduced long-term morbidity, and consequently improved life expectancy in survivors, was previously unestablished.

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In a retrospective analysis with longitudinal follow-up, researchers investigated whether late health outcomes could be altered in patients with ALL through risk stratification of therapy.

Longitudinal data from the Childhood Cancer Survivor Study were included. Patients with data included in this study were diagnosed between 1970 and 1999, with sibling data used for comparison.

Overall, data from 6148 pediatric ALL survivors and 5051 siblings were analyzed. The majority of patients (55%) were diagnosed between 0 and 4 years of age, 3308 (54%) of the patients were male, and 5060 (80%) were non-Hispanic White. Patients were grouped by treatment intensity: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR; 80sHR), standard- or high-risk 1990s-like (90sSR; 90sHR), and relapse/transplantation, regardless of era (R/BMT).

The median number of follow-up years from diagnosis was 22.3 (range, 5-46.4); the 20-year all-cause late mortality rate was 6.6%. Patients in the 90sSR and 90sHR groups had improved health-related late mortality rates compared with those in the 70s group (rate ratios, 0.2 [95% CI, 0.1-0.4] and 0.3 [95% CI, 0.1-0.7], respectively), and had comparable rates to those seen in the wider population (standardized mortality ratios, 1.3 [95% CI, 0.8-2.0] and 1.7 [95% CI, 0.7-3.5], respectively).

In addition, survivors in the 90sSR group had a lower rate of severe chronic conditions than survivors in the 70s group (11% vs 22.5%, respectively).

“Taken together, these results demonstrate that the goal of risk-stratified therapy for children with standard risk ALL, to reduce late morbidity and mortality while maintaining excellent outcomes, has been realized. However, there remains an urgent need to decrease the burden of chronic health conditions experienced in this aging population,” the authors concluded.


Dixon SB, Chen Y, Yasui Y, et al. Reduced morbidity and mortality in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. Published online July 24, 2020. doi:10.1200/JCO.20.00493