Outcomes in adolescent and young adult patients (16 to 30 years) compared to younger patients treated for high-risk B-lymphoblastic leukemia: report from Children's Oncology Group Study AALL0232

Adolescent and young adult (AYA) patients 16-30 years old with high-risk acute lymphoblastic leukemia (HR-ALL) have inferior outcomes compared to younger HR-ALL patients. AALL0232 was a Phase 3 randomized Children's Oncology Group trial for newly diagnosed HR B-ALL (1-30 years). Between 2004 and 2011, 3154 patients enrolled with 3040 eligible and evaluable for induction. AYA patients comprised 20% of patients (16-21 years, n = 551; 22-30 years, n = 46). 5-year event-free survival and overall survival was 65.4 +/- 2.2% and 77.4 +/- 2.0% for AYA patients compared to 78.1 +/- 0.9% and 87.3 +/- 0.7% for younger patients (p < 0.0001). Five-year cumulative incidence of relapse was 18.5 +/- 1.7% for AYA patients and 13.5 +/- 0.7% for younger patients (p = 0.006), largely due to increased marrow relapses (14.0 +/- 1.5% versus 9.1 +/- 0.6%; p < 0.0001). Additionally, induction failure rate was higher in AYA (7.2 +/- 1.1% versus 3.5 +/- 0.4%; p < 0.001) and post-induction remission deaths were significantly higher in AYA (5.7 +/- 1.0% versus 2.4 +/- 0.3%; p < 0.0001). AALL0232 enrolled the largest number of AYA B-ALL patients to date, demonstrating significantly inferior survival and greater rates of treatment-related toxicities compared to younger patients. Although treatment intensification has improved outcomes in younger patients, they have not been associated with the same degree of improvement for older patients.