Effect of Young Age on Outcomes in Pediatric Acute Promyelocytic Leukemia (APL): North American Intergroup Study CALGB 9710 (Alliance)

Purpose: Clinical trials in APL have generally reported similar outcomes for children and adults. However, sub-group analysis of pediatric patients treated on 2 consecutive trials of the European APL group demonstrated that children <5 years (yr) had an increased risk of relapse (Bally et al., JCO, 2012). Here we report the effect of age < 5 yr on outcome for the North American Intergroup Study C9710.

Methods: Outcomes were compared among young children (age <5 yr, n=16) to those of older age (5-12 yr, n=25 and 13-18 yr, n=45) enrolled on C9710. Treatment on C9710 included induction with daunorubicin, cytarabine and ATRA followed by two consolidation cycles with daunorubicin and ATRA and maintenance for one year with ATRA +/- mercaptopurine and methotrexate. Patients of age ≥15 yr were randomized to receive or not receive two 5-week cycles of arsenic trioxide (ATO) before the chemotherapy consolidation. However, analysis in this study of young children compared to those of older age was restricted to patients who did not receive ATO.

Results: Clinical remission (CR) rates were similar between the 3 age groups (age <5 yr= 88%, age 5-12 yr= 80%, age 13-18 yr= 82%; P=0.93). Overall survival (OS) Kaplan-Meier estimates were not significantly different (log rank P=0.84), and 5 yr OS rates were 77% (age <5 yr), 80% (age 5-12 yr), and 84% (age 13-18 yr). Similarly, event-free survival (EFS) Kaplan-Meier estimates were not significantly different (log rank P=0.48), and 5 yr EFS rates were 56% (age <5 yr), 47% (age 5-12 yr), and 59% (age 13-18 yr). Young children did not have a higher relapse rate (5-yr cumulative incidence of relapse by age: <5 yr=29%, 5-12 yr=49%, 13-18 yr=29%).

Conclusions: Results of this intergroup trial demonstrate that ATRA administration during induction, consolidation and maintenance leads to CR rates >80% and 5 yr OS rates >75%. These results are superior to recently published results of pediatric non-APL acute myeloid leukemia and confirm results from the prior APL intergroup trial (INT0129) that demonstrated that ATRA in induction and/or maintenance significantly improved outcomes for pediatric APL (Gregory et al., Ped Blood and Cancer, 2009). Our sub-group analysis showed no association of age with outcomes in children treated with this regimen.