Outcome in adolescent and young adult (AYA) patients compared with younger patients treated for high-risk B-precursor acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group study AALL0232.

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CRA9508 Background: Historically, AYA patients (>16yrs of age) with HR-ALL have an inferior outcome compared to HR-ALL patients 1-15 yrs old, due to increased rates of both relapse and toxicity. Methods: AALL0232 was a phase III randomized trial for patients 1-30 years of age with newly diagnosed B-precursor HR-ALL that utilized a 2 x 2 factorial design with an augmented intensity Berlin-Frankfurt-Münster (BFM) backbone. Patients were randomized to receive dexamethasone versus prednisone during Induction and high dose methotrexate versus escalating Capizzi methotrexate during Interim Maintenance I. A total of 2,574 eligible, evaluable, non-Down Syndrome, non-very high risk patients were randomized between January 2004 and January 2011. AYA patients comprised 20% of this group (n=501; 16-21 yrs: 466 and 22-30 yrs: 35). Results: The 5-yr event-free survival (EFS) and overall survival (OS) rates were 68.0% and 79.8% for AYA patients compared to 80.9% and 88.4% for younger patients (p<0.0001). The 5-yr cumulative incidence of relapse was 21.3% for AYA patients and 13.4% for younger patients (p=0.0018), largely due to higher rate of marrow relapse (15.2% vs. 9.0%; p<0.0007) and not CNS relapse (5.2% vs. 3.7%; p=0.5776). In addition, fewer AYA patients achieved remission, defined as <5% marrow blasts at end induction (97.2% vs. 98.8%; p=0.0134). There was no significant difference in induction mortality between AYA and younger patients, 2.4% vs. 1.8% (p=0.36). However post-induction remission deaths were significantly higher in AYA compared with younger patients, 5.5% vs. 2.1% at 5 years (p<0.0001). Conclusions: This is the largest cohort of AYA ALL patients presented to date and confirms high cure rates for AYA patients treated on pediatric ALL trials. AYA HR-ALL patients had lower EFS and OS compared to younger patients, primarily attributable to both higher rates of marrow relapses and remission deaths. Effective strategies to improve the outcome of AYA patients with HR-ALL should be aimed at both furthering leukemia eradication and lowering toxicity of therapy for this patient population.