Bone pain at leukemia diagnosis and other risk factors for symptomatic osteonecrosis in children with acute lymphoblastic leukemia.

BACKGROUND

Osteonecrosis is a major cause of acute and long-lasting complications of acute lymphoblastic leukemia (ALL) therapy in children. Our study aimed to evaluate the prevalence, characteristics, risk factors, and outcome of osteonecrosis in children with ALL.

PROCEDURE: The cohort included 559 children aged 1-20 years diagnosed with ALL between 2003 and 2018 at two tertiary medical centers in Israel and enrolled in two consecutive protocols: ALL-IC BFM 2002 and AIEOP-BFM ALL 2009. Symptomatic osteonecrosis was prospectively captured as an adverse event.

RESULTS

Osteonecrosis occurred in 51 patients (9.1%). Ninety-four percent of the events were graded as moderate or severe (grades 3-4, Ponte di Legno Toxicity Working Group classification) and multiple bone involvement was common. Full resolution of osteonecrosis was documented in only 16% of the children (median follow-up 4.2 years). Stepwise logistic regression identified five risk factors for osteonecrosis, with a high predictive value (AUC = 0.88): older ageat ALL diagnosis, high-risk ALL group, T-cell immunophenotype, female gender, and a novel risk factor: bone pain at the time of leukemia diagnosis. In addition, osteonecrosis was less common among children of Arab ethnicity. Thrombophilia and an elevated age-adjusted body mass index were not confirmed as risk factors for osteonecrosis.

CONCLUSION

Due to the low rates of osteonecrosis resolution and its debilitating long-term impact, the identification of patients at high risk for osteonecrosis is important for their inclusion in further studies evaluating potential therapeutic adjustments.