Danish cohort study of severe toxicity-free survival following acute lymphoblastic leukemia in patients aged 1-45 years

With increasing survival in acute lymphoblastic leukemia (ALL), long-term toxicities have become a critical aspect. A novel measure, designated Severe Toxicity-free survival (STFS), was developed through international consensus to integrate the most severe, synptomatic organ toxicities in outcome evaluation. A cohort study in Denmark assessed the incidence of 21 predefined severe toxicities in a natiowide cohort of 506 ALL patients aged 1-45 years treated according to the NOPHO ALL2008 protocol. At five years, event-free survival rate was 84.4% (95% CI 81.3-87.7) and severe toxicity-event-free survival rate was 78.4% (74.9-82.1), with significantly lower values in adults aged 18-45 years (61.6%; 52.6-72.2) than in children (82.4% (78.8-86.2; p<0.001). The most common severe toxicities were severe osteonecrosis limiting activities of daily function (n=20) and disabling paralytic and neuropathic conditions (n=16). The authors conclude that these findings highlight a burden of severe, long-term toxicities in ALL survivors overlooked by traditional outcome measures.