Results of a Randomized Augmented Intensification Phase in Acute Lymphoblastic Leukemia in Children in Argentina:
Maria C Riccheri1, Sergio M Gomez2, Alejandra Deana1
1Hospital Nacional Profesor Dr Alejandro Posadas, Haedo, Argentina.
Insights
Intensified therapy for pediatric acute lymphoblastic leukemia (ALL) did not reduce relapse rates in a middle-income country. Standard treatment is recommended, with future research focusing on lowering treatment-related mortality.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- High-income countries show improved outcomes for high-risk pediatric acute lymphoblastic leukemia (ALL) with intensified therapy.
- The efficacy of intensified postinduction therapy in middle-income countries with limited supportive care remains uncertain.
- This study evaluated augmented versus standard Protocol I phase B (IB) in pediatric ALL patients in Argentina.
Purpose of the Study:
- To determine if augmented IB reduces the 5-year cumulative incidence of relapse compared to standard IB in pediatric intermediate- and high-risk ALL.
- To assess treatment-related mortality in both treatment arms.
Main Methods:
- A randomized, phase III multicenter study involving 1060 pediatric patients (1-18 years) with intermediate- or high-risk B- and T-precursor ALL.
- Patients in complete remission post-induction were randomized to either augmented IB (cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, E. coli l-asparaginase, intrathecal methotrexate) or standard IB (cyclophosphamide, 6-mercaptopurine, cytarabine, intrathecal methotrexate).
- The primary outcome was the cumulative incidence of relapse.
Main Results:
- The 5-year cumulative incidence of relapse was similar between standard IB (22.6%) and augmented IB (22.3%) groups (p=0.97).
- Treatment-related mortality was also comparable between the groups (6.5% vs. 7.5%; p=0.45).
Conclusions:
- Augmented IB intensification did not improve relapse outcomes compared to standard IB in pediatric patients with intermediate- and high-risk ALL in Argentina.
- Standard IB is recommended for these patients.
- Future research should prioritize reducing treatment-related mortality in pediatric ALL treatment protocols.
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.
