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Updated: Nov 22, 2025
Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
Reduced-intensity therapy for pediatric lymphoblastic leukemia: impact of residual disease early in remission
Iman Sidhom1,2, Khaled Shaaban2, Sarah H Youssef2
1Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
Insights
Identifying very-low-risk acute lymphoblastic leukemia (ALL) is key. Children with minimal residual disease (MRD) levels between 0.001% and <0.01% had higher relapse rates, suggesting refined MRD criteria for VLR ALL treatment.
Area of Science:
- Pediatric Oncology
- Hematology
- Cancer Research
Background:
- Limited chemotherapy regimens cure approximately 40% of childhood acute lymphoblastic leukemia (ALL) cases.
- Accurate identification of very-low-risk (VLR) ALL patients is challenging.
- Previous studies indicate excellent outcomes for VLR ALL patients with MRD levels <0.01% treated with low-intensity therapy.
Purpose of the Study:
- To investigate the impact of minimal residual disease (MRD) levels between 0.001% and <0.01% on treatment outcomes in VLR ALL.
- To evaluate the effectiveness of reduced-intensity therapy in VLR ALL patients.
- To refine classification criteria for VLR ALL using sensitive MRD assays.
Main Methods:
- A cohort of 200 B-precursor ALL patients with favorable features and day 19 MRD <0.01% received reduced-intensity therapy.
- Minimal residual disease (MRD) levels were assessed by flow cytometry on day 19 and at the end of induction therapy.
- Outcomes including event-free survival, overall survival, and cumulative incidence of relapse (CIR) were analyzed.
Main Results:
- The 5-year event-free survival was 89.5% and overall survival was 95.5%.
- The 5-year cumulative incidence of relapse (CIR) was 7%.
- Patients with day 19 MRD levels between 0.001% and <0.01% exhibited a significantly higher 5-year CIR (17.2%) compared to those with undetectable MRD (5.3%).
Conclusions:
- Children with VLR ALL can be successfully treated with decreased-intensity chemotherapy.
- Current classification criteria for VLR ALL may be further refined by incorporating more sensitive MRD assays.
- The study highlights the prognostic significance of MRD levels between 0.001% and <0.01% in VLR ALL.
Abstract:
Legacy data show that ∼40% of children with acute lymphoblastic leukemia (ALL) were cured with limited antimetabolite-based chemotherapy regimens. However, identifying patients with very-low-risk (VLR) ALL remains imprecise. Patients selected based on a combination of presenting features and a minimal residual disease (MRD) level <0.01% on day 19 of induction therapy had excellent outcomes with low-intensity treatment. We investigated the impact of MRD levels between 0.001% and <0.01% early in remission induction on the outcome of VLR ALL treated with a low-intensity regimen. Between October of 2011 and September of 2015, 200 consecutive patients with B-precursor ALL with favorable clinicopathologic features and MRD levels <0.01%, as assessed by flow cytometry in the bone marrow on day 19 and at the end of induction therapy, received reduced-intensity therapy. The 5-year event-free survival was 89.5% (± 2.2% standard error [SE]), and the overall survival was 95.5% (± 1.5% SE). The 5-year cumulative incidence of relapse (CIR) was 7% (95% confidence interval, 4-11%). MRD levels were between 0.001% and <0.01% on day 19 in 29 patients. These patients had a 5-year CIR that was significantly higher than that of patients with undetectable residual leukemia (17.2% ± 7.2% vs 5.3% ± 1.7%, respectively; P = .02). Our study shows that children with VLR ALL can be treated successfully with decreased-intensity therapy, and it suggests that the classification criteria for VLR can be further refined by using a more sensitive MRD assay.
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