What is the typical chemotherapy regimen for Acute Lymphoblastic Leukemia (ALL) induction?

ALL Induction Chemotherapy Regimen

The standard induction regimen for acute lymphoblastic leukemia consists of a 4-drug backbone: vincristine, an anthracycline (daunorubicin or doxorubicin), a corticosteroid (prednisone or dexamethasone), and L-asparaginase/pegaspargase, administered over 4 weeks to achieve complete remission. 1, 2

Core Induction Components

The 4-drug induction regimen includes:

• Vincristine: 1.4 mg/m² IV weekly (maximum 2 mg per dose) 3
• Anthracycline: Daunorubicin 25-30 mg/m² IV weekly or doxorubicin at equivalent dosing 1, 3
• Corticosteroid: Either prednisone or dexamethasone (see critical considerations below) 4, 1
• L-asparaginase: Pegaspargase 2,500 IU/m² IV for patients ≤21 years or 2,000 IU/m² for patients >21 years, administered no more frequently than every 14 days 5

For standard-risk pediatric patients only, a 3-drug induction without anthracyclines may be considered. 1, 2

Critical Corticosteroid Decision: Dexamethasone vs. Prednisone

This represents a key clinical trade-off requiring careful consideration:

Dexamethasone advantages:

• Significantly reduces CNS relapse risk (RR 0.53,95% CI 0.44-0.65) 4
• Improves event-free survival (RR 0.80,95% CI 0.68-0.94) 4
• Superior CNS penetration compared to prednisone 4, 1

Dexamethasone disadvantages:

• Significantly increases induction mortality (RR 2.31,95% CI 1.46-3.66) 4
• Higher risk of neuropsychiatric adverse events (RR 4.55,95% CI 2.45-8.46) 4
• Increased myopathy risk (RR 7.05,95% CI 3.00-16.58) 4
• No proven overall survival advantage 4, 1

Clinical recommendation: Use prednisone for very young children (especially <1 year) and older adults to minimize toxicity risk, particularly osteonecrosis. 3 Use dexamethasone for patients at higher risk of CNS involvement where the CNS protection benefit outweighs toxicity concerns. 1

Common Alternative Regimens

Hyper-CVAD regimen (particularly for adults):

• Alternating "A" cycles: hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone 4
• Alternating "B" cycles: high-dose methotrexate and cytarabine 4
• Total of 8 cycles with integrated CNS prophylaxis 4

Linker 4-drug regimen (adolescents and adults):

• Vincristine, daunorubicin, prednisone, and asparaginase 4
• Achieved 5-year EFS of 48% and OS of 47% in the original study 4
• Can be intensified with pegaspargase, cyclophosphamide, and targeted agents 4

MRC UKALL XII/ECOG E2993 (large multicenter trial):

• Phase I (4 weeks): vincristine, daunorubicin, prednisone, L-asparaginase 4
• Phase II (4 weeks): cyclophosphamide, cytarabine, oral mercaptopurine, intrathecal methotrexate 4
• Followed by intensification with high-dose methotrexate and L-asparaginase 4

Essential Concurrent Therapy

CNS prophylaxis must begin during induction and continue throughout all treatment phases:

• Intrathecal chemotherapy with methotrexate, cytarabine, and corticosteroids (triple intrathecal therapy) 2, 3
• High-dose systemic methotrexate during consolidation 4, 2
• Consider cranial irradiation only for patients with CNS leukemia at diagnosis 4

Age-Specific Modifications

Patients ≥65 years or with substantial comorbidities:

• Reduce treatment intensity to minimize toxicity 1, 2
• Low-intensity options: vincristine plus prednisone or POMP regimen 2
• Moderate-intensity options: ALLOLD07, EWALL, GMALL, or GRAALL regimens 2
• Critical caveat: Chronologic age alone is a poor surrogate for determining fitness; assess functional status and comorbidities 1

Adolescents and young adults (AYA):

• Benefit from pediatric-inspired protocols with modifications including cyclophosphamide addition 1
• GRAALL-2014 protocol showed reduced induction death rate (3% vs 11%) compared to earlier protocols by reducing chemotherapy intensity in patients aged 45-59 years 4

Premedication Requirements

Before pegaspargase administration:

• Acetaminophen 30-60 minutes prior 5
• H1-receptor blocker (diphenhydramine) 30-60 minutes prior 5
• H2-receptor blocker (famotidine) 30-60 minutes prior 5
• This reduces risk and severity of infusion and hypersensitivity reactions 5

Expected Outcomes and Monitoring

Complete remission rates:

• Adults with standard 4-drug induction: 78-93% 4, 6, 7
• Pediatric patients: 86-92% depending on risk stratification 4

Monitor at least weekly during induction:

• Bilirubin and transaminases 5
• Glucose levels 5
• Clinical examinations until recovery from each cycle 5

Common Pitfalls to Avoid

• Do not use vincristine doses >2 mg regardless of body surface area calculation 3
• Do not administer pegaspargase more frequently than every 14 days due to prolonged enzymatic activity in adults 4, 5
• Do not omit CNS prophylaxis even in patients without CNS involvement at diagnosis—this is essential throughout all treatment phases 4, 2
• Do not delay MRD assessment at end of induction, as this is the strongest prognostic factor guiding subsequent therapy intensity 3, 8