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Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
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The Children Leukemia Group: 30 years of research and achievements
1AZK-VUB, Laarbeeklaan 101, B-1090, Brussels, Belgium.
Insights
The EORTC Children Leukemia Group (CLG) adapted the BFM treatment strategy for childhood acute lymphoblastic leukemia (ALL). Key findings include optimizing chemotherapy and the prognostic value of minimal residual disease assessment.
Area of Science:
- Pediatric Hematology Oncology
- Clinical Trials in Leukemia
- Childhood Cancer Research
Background:
- The EORTC Children Leukemia Group (CLG) adopted the Berlin-Frankfurt-Munster (BFM) treatment strategy for childhood acute lymphoblastic leukemia (ALL) after its demonstrated efficacy.
- The CLG aimed to refine and validate the BFM regimen through its own clinical trials.
Observation:
- Standard risk patients' outcomes were not compromised by omitting cyclophosphamide during consolidation and reconsolidation.
- Cranial radiotherapy was found to be unnecessary for medium- and high-risk patients undergoing high-dose methotrexate (MTX) therapy.
- E-Coli L-Asparaginase proved more effective than Erwinia L-Asparaginase within the BFM regimen's dose schedule.
- Adding monthly intravenous 6-mercaptopurine to maintenance chemotherapy was detrimental to patient outcomes.
- Quantitative polymerase chain reaction (PCR) assessment of minimal residual disease post-induction is feasible and a strong prognostic indicator.
Findings:
- Optimized chemotherapy regimens by identifying unnecessary components (cyclophosphamide, cranial radiotherapy) and less effective agents (Erwinia L-Asparaginase).
- Demonstrated the detrimental effect of adding 6-mercaptopurine to maintenance therapy.
- Validated minimal residual disease assessment via quantitative PCR as a reliable prognostic factor in cooperative settings.
Implications:
- Refined treatment protocols for childhood ALL, potentially reducing toxicity and improving outcomes.
- Established minimal residual disease monitoring as a critical tool for risk stratification and treatment adaptation.
- Contributed valuable data to international collaborative efforts like the I-BFM Study Group and meta-analyses.
Abstract:
The EORTC Children Leukemia Group (CLG) is part of the offspring of the EORTC Hemopathies Working Party which in 1978 split into a paediatric and to an 'adult' branch. At that time, the Berlin-Frankfurt-Munster (BFM) designed by H. Riehm for acute lymphoblastic leukaemia (ALL) appeared much more efficacious than all others and the CLG decided to adapt that treatment strategy for its own clinical trials. The main results of these may be summarised as follows:for standard risk patients, the deletion of cyclophosphamide from consolidation and reconsolidation courses does not jeopardise the patient's outcomefor medium- and high-risk patients receiving high-dose methotrexate (MTX), cranial radiotherapy is superfluouswith the dose scheduling of the BFM regimen, E-Coli L-Asparaginase is more efficacious than Erwinia L-Asparaginasethe addition of monthly intravenous (i.v.) 6-mercaptopurine to conventional maintenance chemotherapy is detrimentalthe assessment by quantitative polymerase chain reaction (PCR) of minimal residual disease at completion of induction is feasible in a cooperative setting and can be used as a powerful and independent prognostic factor. The CLG also conducted clinical studies of acute myeloblastic leukaemia. Since 1989, lymphoblastic non-Hodgkin's lymphomas have been treated within the ALL trials. The CLG collaborates with other Groups within the I-BFM Study Group and participants in the meta-analytic studies conducted by the Oxford team by the Oxford Children ALL Collaborative Group.
