Results of a Randomized Augmented Intensification Phase in Acute Lymphoblastic Leukemia in Children in Argentina: GATLA 2010 ALL IC Trial.

BACKGROUND

Intensified postinduction therapy improves outcomes for high-risk pediatric patients with acute lymphoblastic leukemia (ALL) in high-income countries. However, benefits are uncertain in middle-income countries where supportive care is often limited. The primary objective was to determine if augmented protocal I phase B (IB) reduced the 5-year cumulative incidence of relapse compared with standard IB among newly diagnosed pediatric patients with intermediate- and high-risk (IR and HR) ALL in a middle-income country.

METHODS

This was a randomized, phase III multicenter study conducted in 30 centers from GATLA group in Argentina, as part of International BFM study group ALLIC. We included newly diagnosed pediatric patients with ALL 1-18 years of age with IR or HR B- and T-precursor ALL. Only patients who were in complete remission at end induction were randomized to augmented IB versus standard IB. Augmented IB consisted of cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, E. coli l-asparaginase and intrathecal methotrexate. Standard IB consisted of cyclophosphamide, 6-mercaptopurine, cytarabine, and intrathecal methotrexate. The primary outcome was the cumulative incidence of relapse.

RESULTS

There were 1060 patients randomized to standard IB (n = 527) and augmented IB (n = 533). The 5-year cumulative incidence of relapse (±standard error) was not significantly different by group (22.6 ± 0.2 vs. 22.3 ± 0.1%; p = 0.97) for standard IB and augmented IB, respectively. Treatment-related mortality (TRM) was 6.5 ± 0.1 and 7.5 ± 0.1%; p = 0.45, respectively.

CONCLUSIONS

Among newly diagnosed pediatric patients with IR and HR ALL treated in Argentina, postinduction intensification with augmented IB did not improve outcomes compared with standard IB. Standard IB should be used for these patients. Future trials should focus on reducing TRM.