Outcomes in children with first-relapsed acute lymphoblastic leukemia in Japan: Results from JCCG Study JPLSG-ALL-R08
Junko Yamanaka1, Chitose Ogawa2, Ayumu Arakawa2
1Department of Pediatrics, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
Insights
This study shows that ALL-REZ BFM-type treatment is effective for children with first-relapsed acute lymphoblastic leukemia (ALL) in Japan. Risk stratification using BFM-S classification and minimal residual disease (MRD) helps guide treatment decisions for better outcomes.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- The Berlin-Frankfurt-Münster (BFM)-S classification is a key prognostic factor for childhood acute lymphoblastic leukemia (ALL) relapse.
- Minimal residual disease (MRD) monitoring after induction therapy significantly impacts survival in pediatric ALL patients.
- The ALL-R08 study was the first nationwide prospective multicenter trial in Japan for children with first-relapsed ALL.
Purpose of the Study:
- To evaluate the effectiveness of risk stratification based on BFM-S classification and MRD response in children with first-relapsed ALL.
- To assess treatment outcomes in a nationwide cohort of Japanese children with first-relapsed ALL.
- To compare outcomes between different risk groups and treatment strategies in the ALL-R08 study.
Main Methods:
- The ALL-R08 study included an observational part (ALL-R08-I) and a clinical trial (ALL-R08-II) for non-T-ALL S2 risk group.
- In ALL-R08-II, patients with MRD ≥10⁻³ received allogeneic hematopoietic stem cell transplantation (allo-HCT), while those with MRD <10⁻³ or isolated extramedullary relapse received chemotherapy.
- Data on BFM-S classification, MRD levels, and treatment strategies were collected and analyzed.
Main Results:
- In ALL-R08-I, 3-year event-free survival (EFS) varied significantly by risk group: S1 (83%), S2 (37%), S3 (28%), S4 (14%), and post-HCT (0%).
- In the ALL-R08-II trial, 3-year EFS was similar for patients with post-induction MRD <10⁻³ (70%) and ≥10⁻³ (68%).
- A total of 163 patients were enrolled, with 82 in ALL-R08-I and 81 in ALL-R08-II.
Conclusions:
- ALL-REZ BFM-type treatment demonstrates comparable effectiveness for children with first-relapsed ALL treated under Japanese frontline protocols versus BFM-type frontline protocols.
- Risk stratification using BFM-S classification and MRD response is crucial for managing childhood ALL relapse.
- The findings support the use of standardized treatment protocols for relapsed pediatric ALL.
Background/Objectives:
The Berlin-Frankfurt-Münster (BFM)-S classification is a crucial prognostic indicator in children experiencing first-relapsed acute lymphoblastic leukemia (ALL). Early molecular response to therapy, evaluated by measurable/minimal residual disease (MRD), has a significant impact on the survival of patients with childhood ALL. Applying risk stratification based on the BFM-S classification and MRD response after induction, the first nationwide prospective multicenter study, ALL-R08, was conducted in children with first-relapsed ALL in Japan.
Methods:
The ALL-R08 study comprised two parts: ALL-R08-I, an observational study aimed at obtaining an overall picture of outcomes in first-relapsed childhood ALL, and ALL-R08-II, a clinical trial for the non-T-ALL S2 risk group. In ALL-R08-II, patients with an MRD level of ≥10-3 at the end of induction therapy were assigned to undergo allogeneic hematopoietic stem cell transplantation (allo-HCT), whereas those with an MRD level less than 10-3 and isolated extramedullary relapse continued to receive chemotherapy.
Results:
In total, 163 patients were enrolled in the ALL-R08 study, and 82 and 81 patients were enrolled in the ALL-R08-I and the ALL-R08-II, respectively. In ALL-R08-I, the probability of 3-year event-free survival (EFS) for patients with S1, S2, S3, S4, and post-HCT groups was 83% ± 15%, 37% ± 11%, 28% ± 8%, 14% ± 7%, and 0%, respectively. In the ALL-R08-II trial, 3-year EFS in patients with post-induction MRD less than 10-3 and ≥10-3 was 70% ± 9% (n = 27) and 68% ± 8% (n = 31) (p = .591), respectively.
Conclusions:
ALL-REZ BFM-type treatment is equally effective for children with first-relapsed ALL treated according to the Japanese frontline protocols and for children with first-relapsed ALL treated according to the BFM-type frontline protocols.
