Related Experiment Video
Updated: Dec 10, 2025
Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial
Daisuke Tomizawa1, Takako Miyamura2, Toshihiko Imamura3
1Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Insights
Infants with KMT2A-r acute lymphoblastic leukemia (ALL) have a poor prognosis, but a new trial improved outcomes with risk stratification and intensive chemotherapy. Early clearance of minimal residual disease (MRD) is crucial for favorable results in infant ALL.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- Infants with KMT2A gene rearrangement (KMT2A-r) acute lymphoblastic leukemia (ALL) historically face a dismal prognosis.
- Previous efforts in Japan using hematopoietic stem cell transplantation (HSCT) for KMT2A-r ALL showed only modest outcome improvements.
Purpose of the Study:
- To evaluate a modified chemotherapy regimen and risk stratification strategy for infants with ALL in the MLL-10 trial.
- To assess the impact of intensive chemotherapy and the role of minimal residual disease (MRD) on outcomes for KMT2A-r ALL.
Main Methods:
- Infants with ALL were stratified into low (LR), intermediate (IR), and high risk (HR) groups based on KMT2A status, age, and CNS leukemia.
- KMT2A-r patients received modified chemotherapy (AALL0631) with high-dose cytarabine; HSCT was reserved for HR patients.
- Minimal residual disease (MRD) levels were evaluated to assess prognostic significance.
Main Results:
- The 3-year event-free survival (EFS) for KMT2A-r ALL (IR + HR) was 66.2%, compared to 93.3% for germline KMT2A (KMT2A-g) ALL (LR).
- EFS rates were 94.4% for IR and 56.6% for HR KMT2A-r ALL patients.
- Female sex and MRD ≥0.01% post-consolidation were significant poor prognostic factors.
Conclusions:
- The implemented risk stratification and intensive chemotherapy effectively improved outcomes for infants with KMT2A-r ALL, reducing the need for HSCT in some cases.
- Early achievement of MRD negativity is associated with favorable outcomes and should be integrated into future infant ALL risk stratification.
- The study highlights the importance of MRD monitoring in tailoring treatment for high-risk infant ALL.
Abstract:
The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children's Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n = 15), IR (n = 19), or HR (n = 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ≥0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.
