Development of osteonecrosis and improved survival in B-ALL: results of Children’s Oncology Group Trial AALL0232

Mattano LA Jr, Devidas M, Loh ML, Raetz EA, Chen Z, Winick NJ, Hunger SP, Carroll WL, Larsen EC. Development of osteonecrosis and improved survival in B-ALL: results of Children’s Oncology Group Trial AALL0232. Leukemia. 2024 Feb;38(2):258-265. doi: 10.1038/s41375-023-02099-1. Epub 2023 Dec 7. PubMed PMID: 38062123; PubMed Central PMCID: PMC11235418.

Osteonecrosis is a significant toxicity of acute lymphoblastic leukemia (ALL) therapy. In retrospective analyses, superior event-free survival was noted among affected adolescents in an earlier trial. We prospectively assessed osteonecrosis incidence, characteristics, and risk factors in patients 1–30 years with newly diagnosed high-risk B-ALL on COG AALL0232. Patients were randomized to induction dexamethasone vs prednisone, and interim maintenance high-dose methotrexate vs escalating-dose Capizzi methotrexate/pegaspargase. Event-free and overall survival were compared between patients with/without imaging-confirmed osteonecrosis. Osteonecrosis developed in 322/2730 eligible, evaluable patients. The 5-year cumulative incidence was 12.2%. Risk was greater in patients ≥10 years (hazard ratio [HR], 7.23; P<0.0001), particularly females (HR, 1.37; P=0.0057), but lower in those with asparaginase allergy (HR, 0.60; P=0.0077). Among rapid early responders ≥10 years, risk was greater with dexamethasone (HR, 1.84; P=0.0003) and with prednisone/Capizzi (HR, 1.45; P=0.044), even though neither therapy was independently associated with improved survival. Patients with osteonecrosis had higher 5-year event-free (HR, 0.51; P<0.0001) and overall survival (HR, 0.42; P<0.0001), and this was directly attributable to reduced relapse rates (HR, 0.57; P=0.0014). Osteonecrosis in high-risk B-ALL patients is associated with improved survival, suggesting an important role for host factors in mediating both toxicity and enhanced efficacy of specific therapies.