Outcomes in children with first‐relapsed acute lymphoblastic leukemia in Japan: Results from JCCG Study JPLSG‐ALL‐R08

Abstract

Background/objectivesThe 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.MethodsThe 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.ResultsIn 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.ConclusionsALL‐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.