Related Experiment Video
Updated: Jul 13, 2026
Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an
Rob Pieters1, Martin Schrappe2, Paola De Lorenzo3
1Dutch Childhood Oncology Group (DCOG; Netherlands) Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands.
Insights
A novel hybrid treatment protocol improved outcomes for infant acute lymphoblastic leukaemia (ALL). Delayed chemotherapy intensification did not benefit patients, but specific genetic and clinical factors predicted poorer outcomes in infants with ALL.
Area of Science:
- Pediatric Oncology
- Hematologic Malignancies
- Clinical Trials
Background:
- Infant acute lymphoblastic leukaemia (ALL) is rare with poorer outcomes compared to older children.
- A new hybrid treatment protocol combining ALL and acute myeloid leukaemia (AML) elements was investigated.
- Prognostic factors influencing infant ALL outcomes were identified.
Purpose of the Study:
- To evaluate a novel hybrid treatment protocol for infants (0-12 months) with ALL.
- To identify prognostic factors associated with treatment outcomes in this population.
- To assess the efficacy of a late chemotherapy intensification course via a randomized trial.
Main Methods:
- An international study enrolled 482 infants (0-12 months) between 1999-2005.
- Patients received a hybrid regimen based on ALL protocols with AML elements, stratified by prednisone response.
- A subset of patients in remission were randomized to standard or intensified late chemotherapy.
Main Results:
- The hybrid protocol resulted in a 4-year event-free survival (EFS) of 47.0% in the initial cohort.
- Late intensification did not significantly improve disease-free survival (DFS) (60.9% vs. 57.0%, p=0.81).
- MLL gene rearrangements, high white blood cell count, age <6 months, and poor prednisone response predicted inferior outcomes.
Conclusions:
- The hybrid protocol demonstrated promising EFS for infant ALL, particularly in those with poor prednisone response.
- Delayed intensification chemotherapy did not confer additional benefit to patients.
- Identifying prognostic factors is crucial for optimizing treatment strategies in infant ALL.
Background:
Acute lymphoblastic leukaemia in infants younger than 1 year is rare, and infants with the disease have worse outcomes than do older children. We initiated an international study to investigate the effects of a new hybrid treatment protocol with elements designed to treat both acute lymphoblastic leukaemia and acute myeloid leukaemia, and to identify any prognostic factors for outcome in infants. We also did a randomised trial to establish the value of a late intensification course.
Methods:
Patients aged 0-12 months were enrolled by 17 study groups in 22 countries between 1999 and 2005. Eligible patients were stratified for risk according to their peripheral blood response to a 7-day prednisone prophase, and then given a hybrid regimen based on the standard protocol for acute lymphoblastic leukaemia, with some elements designed for treatment of acute myeloid leukaemia. Before the maintenance phase, a subset of patients in complete remission were randomly assigned to receive either standard treatment or a more intensive chemotherapy course with high-dose cytarabine and methotrexate. The primary outcomes were event-free survival (EFS) for the initial cohort of patients and disease-free survival (DFS) for the patients randomly assigned to a treatment group. Data were analysed on an intention-to-treat basis. This trial was registered with ClinicalTrials.gov, number NCT 00015873, and at controlled-trials.com, number ISRCTN24251487.
Findings:
In the 482 enrolled patients who underwent hybrid treatment, 260 (58%) were in complete remission at a median follow-up of 38 (range 1-78) months, and EFS at 4 years was 47.0% (SE 2.6, 95% CI 41.9-52.1). Of 445 patients in complete remission after 5 weeks of induction treatment, 191 were randomised: 95 patients to receive a late intensification course, and 96 to a control group. At a median follow-up of 42 (range 1-73) months, 60 patients in the treatment group and 57 controls were disease-free. DFS at 4 years did not differ between the two groups (60.9% [SE 5.2] for treatment group vs 57.0% [5.5] for controls; p=0.81). During the intensification phase, of 71 patients randomly assigned to the treatment group, and for whom toxicity data were available, 35 (49%) had infections, 21 (30%) patients had mucositis, 22 (31%) patients had toxic effects on the liver, and 2 (3%) had neurotoxicity. All types of rearrangements in the (mixed lineage leukaemia) MLL gene, very high white blood cell count, age of younger than 6 months, and a poor response to the prednisone prophase were independently associated with inferior outcomes.
Interpretation:
Patients treated with our hybrid protocol, and especially those who responded poorly to prednisone, had higher EFS than most reported outcomes for treatment of infant ALL. Delayed intensification of chemotherapy did not benefit patients.
