CALGB 9111 Protocol for Acute Lymphoblastic Leukemia
The CALGB 9111 protocol is a high-intensity regimen for acute lymphoblastic leukemia (ALL) that includes a 5-drug induction regimen (vincristine, daunorubicin, prednisone, L-asparaginase, and cyclophosphamide) with the addition of granulocyte colony-stimulating factor (G-CSF) to reduce neutropenia-related complications. 1
Protocol Components and Structure
Induction Phase
- Based on the CALGB 8811 regimen with the addition of G-CSF
- 5-drug combination:
- Vincristine
- Daunorubicin
- Prednisone
- L-asparaginase
- Cyclophosphamide
- G-CSF administration during neutropenic periods 1
Key Benefits of G-CSF Addition
- Significantly shorter duration of severe neutropenia (p<0.001)
- Reduced thrombocytopenia duration (p=0.003)
- Earlier hospital discharge (p=0.02)
- Lower induction mortality, particularly in older patients (10% vs 25% without G-CSF) 1
Patient Selection and Considerations
Appropriate Candidates
- Adults with newly diagnosed ALL
- Primarily recommended for patients <65 years with good performance status and minimal comorbidities 1
- May be considered for fit older adults, though with dose modifications
Risk Stratification
- For patients with Ph-negative ALL, high-risk features include:
- Elevated WBC count (≥30 × 10^9/L for B-cell lineage; ≥100 × 10^9/L for T-cell lineage)
- Hypodiploidy
- MLL rearrangements 1
Efficacy and Outcomes
The CALGB 9111 study demonstrated:
- Improved complete remission rates with G-CSF (81% vs 55% in older patients)
- Median overall survival of 12 months in elderly patients
- 3-year overall survival of 17% in elderly patients 1
Toxicity Management
Common Toxicities
- Myelosuppression
- Infection risk during neutropenic periods
- L-asparaginase-related hepatotoxicity
- Steroid-related complications
Supportive Care
- G-CSF administration is critical to reduce neutropenia-related complications
- Appropriate antimicrobial prophylaxis
- Close monitoring of hepatic function
- CNS prophylaxis is incorporated into the regimen 2
Modern Context and Alternatives
The NCCN Guidelines (2024) classify CALGB 9111 as a high-intensity regimen option for:
- Patients <65 years with Ph-negative ALL
- Select fit patients ≥65 years with Ph-negative ALL 1
Alternative regimens by intensity level:
- High-intensity: ECOG 1910, dose-adjusted hyper-CVAD
- Moderate-intensity: ALLOLD07, EWALL, GMALL, GRAALL, modified DFCI 91-01
- Low-intensity: Vincristine and prednisone, POMP 1, 2
Post-Induction Management
After induction with CALGB 9111:
- MRD assessment is critical for determining subsequent therapy
- If MRD positive: Consider blinatumomab (preferred) or inotuzumab ozogamicin
- Consolidation with allogeneic HCT should be considered for high-risk patients
- Maintenance therapy typically follows consolidation 1, 2
Important Considerations
- Treatment should be administered in specialized centers with experience in managing ALL
- Adequate supportive care is essential to minimize toxicities
- CNS prophylaxis is a critical component of ALL treatment
- MRD assessment guides post-induction therapy decisions 2
Pitfalls and Caveats
- Higher treatment-related mortality compared to less intensive regimens
- May not be appropriate for older or less fit patients
- Requires careful monitoring and aggressive supportive care
- Consider dose modifications for patients ≥60 years (as in the original protocol with 33% reduction of daunorubicin and cyclophosphamide doses) 1
- More recent treatment approaches may offer better outcomes with less toxicity for certain patient populations 1, 2