What is the mBFM (methotrexate, bleomycin, fluorouracil, mitoxantrone) regimen used for?

mBFM Regimen: A Chemotherapy Protocol for Pediatric B-cell Malignancies

The mBFM (methotrexate, bleomycin, fluorouracil, mitoxantrone) regimen is primarily used for treating pediatric B-cell acute lymphoblastic leukemia (B-ALL) and mature B-cell non-Hodgkin lymphomas, particularly Burkitt lymphoma.

Background and Clinical Applications

The mBFM regimen represents a modification of the original Berlin-Frankfurt-Munster (BFM) protocol, which has been a cornerstone in treating pediatric hematologic malignancies. The BFM protocols have demonstrated significant efficacy in:

• Pediatric B-cell acute lymphoblastic leukemia (B-ALL)
• Burkitt lymphoma and other mature B-cell non-Hodgkin lymphomas
• Some cases of T-cell lymphoblastic lymphoma

Protocol Components and Administration

The mBFM regimen typically includes:

• Methotrexate: High-dose (5 g/m²) administered as a 24-hour infusion 1
• Bleomycin: Used in specific phases of the protocol
• Fluorouracil (5-FU): Administered intravenously
• Mitoxantrone: An anthracycline derivative that may replace or supplement doxorubicin in some protocols

The protocol is administered in multiple phases:

1. Cytoreductive prephase: Often includes prednisone and cyclophosphamide
2. Induction: Intensive chemotherapy to achieve remission
3. Consolidation: Further therapy to eliminate residual disease
4. Maintenance: Extended therapy to prevent relapse

Efficacy and Outcomes

The BFM protocols have shown impressive results in pediatric populations:

• 5-year event-free survival rates of 78-85% for standard and medium-risk groups 2
• Complete remission rates of approximately 95% in adult studies comparing BFM to other regimens 3
• Particularly high efficacy in B-ALL, with 5-year survival rates reaching 71% even in adult patients 4

Risk Stratification

Treatment intensity is adjusted based on risk factors 5:

• Minimal Residual Disease (MRD): Critical prognostic factor at end of induction
• CNS involvement: May require additional intrathecal therapy
• Response to initial therapy: Poor early response indicates higher risk

Toxicity Management

Common toxicities that require monitoring include:

• Myelosuppression: Particularly leukopenia (67% grade 3-4) 6
• Liver enzyme elevations: Generally mild and manageable 3
• Tumor lysis syndrome: Especially in patients with high tumor burden
• CNS toxicity: Reduced with modern protocols using lower-dose cranial radiation

Modern Protocol Considerations

Current adaptations of the BFM protocol often include:

• Rituximab addition: For CD20-positive B-cell malignancies, improving outcomes in high-risk patients 7
• Nelarabine incorporation: For T-ALL, especially in MRD-positive patients 5
• Bortezomib: Has shown benefit in T-cell lymphoblastic lymphoma but not leukemia 5

Comparison to Alternative Regimens

The NCCN guidelines recognize several effective regimens for pediatric B-cell malignancies 7:

• BFM-based protocols: Including mBFM variants
• FAB/LMB96: Another effective regimen, particularly for Group A and B patients
• COG ANHL1131: With or without rituximab based on risk stratification
• Hyper-CVAD: Alternative regimen, particularly in adult patients

Conclusion

The mBFM regimen represents an effective, risk-adapted approach to treating pediatric B-cell malignancies with high cure rates. Modern adaptations continue to refine the protocol to maximize efficacy while minimizing toxicity.