Journal: Leukemia
This study evaluated long-term, severe treatment-related toxicities in a nationwide cohort of 506 patients aged 1–45 years with acute lymphoblastic leukemia treated on the NOPHO ALL2008 protocol.
Using a newly defined outcome metric, Severe Toxicity-free Survival (STFS)—which captures 21 predefined, symptomatic, organ-related toxicities—the investigators compared traditional event-free survival (EFS) with STFS at 5 years:
- 5-year EFS: 84.4% (95% CI 81.3–87.7)
- 5-year STFS: 78.4% (95% CI 74.9–82.1)
Key findings by age group:
- Adults (18–45 years) had significantly worse STFS than children (61.6% vs 82.4%; log-rank p < 0.001), indicating a higher burden of serious late effects despite similar traditional outcomes.
Most frequent severe toxicities:
- Function-limiting osteonecrosis (n=20)
- Disabling paralytic and neuropathic conditions (n=16)
Exploratory age-stratified analyses suggested that adolescents (10–17 years) had a risk of severe toxicities comparable to adults, identifying this as a particularly vulnerable group.
The authors conclude that substantial, clinically meaningful late toxicities are not captured by standard outcome metrics and that STFS should be integrated into future ALL trials to enable more comprehensive assessment and comparison of treatment strategies.