How is prednisone used (dose, schedule, duration, side‑effect profile) in induction therapy for acute lymphoblastic leukemia, and when should dexamethasone be used instead?

Prednisone in Acute Lymphoblastic Leukemia Induction Therapy

Prednisone is administered at 60 mg/m² per day for 3-4 weeks during induction therapy as part of a multi-drug backbone, but dexamethasone (6-10 mg/m² per day) should be used instead in most patients because it reduces CNS relapse by approximately 47% and improves event-free survival, despite carrying higher toxicity risks. 1, 2

Standard Prednisone Dosing and Schedule

Induction Phase:

• Dose: 60 mg/m² per day orally 1, 3
• Duration: 21-28 days (typically days 1-8 and 15-22, or continuous for 3 weeks plus tapering) 1, 3, 4
• Combination: Always given with vincristine, anthracyclines (daunorubicin or doxorubicin), and L-asparaginase/pegaspargase 1
• Additional agents: May include cyclophosphamide in 5-drug regimens (CALGB protocols) 1

Maintenance Phase:

• Dose: Monthly pulses (dose varies by protocol, typically 40-60 mg/m² daily for 5 days) 1, 5
• Duration: 2-3 years total from diagnosis 1, 5
• Combination: Given with daily 6-mercaptopurine and weekly methotrexate, plus monthly vincristine 1, 5

Prednisone Side Effect Profile

Common toxicities include:

• Hyperglycemia and weight gain 5
• Mood changes and behavioral disturbances 5
• Increased infection risk (though lower than dexamethasone) 1, 2
• Fluid retention due to mineralocorticoid activity 2

Critical advantage: Prednisone has significantly better tolerability for long-term use compared to dexamethasone, with lower rates of induction mortality (0.9% vs 2.5%), neuropsychiatric events, and myopathy 1, 2, 4

When to Use Dexamethasone Instead of Prednisone

Dexamethasone (6-10 mg/m² per day) is the preferred corticosteroid in ALL induction therapy and should be used in the following clinical scenarios: 1, 2

Primary Indications for Dexamethasone:

1. CNS relapse prevention priority: Dexamethasone has 5-6 times greater glucocorticoid potency and superior CNS penetration, reducing isolated CNS relapse risk by 47-50% (RR 0.53; 95% CI 0.44-0.65) 1, 2

2. T-cell ALL with good prednisone response: This is the only subgroup where dexamethasone demonstrates overall survival benefit (91.4% vs 82.6% at 5 years, P=0.036) 1, 4

3. Standard practice in most modern protocols: NCCN explicitly recommends dexamethasone as the corticosteroid of choice across age groups when CNS relapse prevention is prioritized 1, 2

Relative Contraindications to Dexamethasone (Use Prednisone Instead):

1. History of psychiatric disorders: Dexamethasone carries 4.55-fold higher risk of neuropsychiatric adverse events (RR 4.55; 95% CI 2.45-8.46) 1, 2

2. High osteonecrosis risk: Adolescents and young adults are particularly vulnerable; dexamethasone at 10 mg/m² per day significantly increases this risk 1, 2

3. Frail or elderly patients: Dexamethasone increases induction mortality 2.31-fold (RR 2.31; 95% CI 1.46-3.66) 1, 2

4. Precursor B-cell ALL: In this large subgroup, dexamethasone reduces salvageable relapses but worsens survival after relapse, negating overall survival benefit 4

5. Pediatric patients with specific risk factors: Some pediatric protocols may favor prednisone in lower-risk patients to minimize toxicity 1

Critical Evidence Nuances

The dexamethasone vs prednisone debate reveals important contradictions:

• Event-free survival: Dexamethasone consistently improves EFS (83.9% vs 80.8% at 5 years, P=0.024) 4
• Overall survival: No difference in total cohort (90.3% vs 90.5%), except T-ALL with good prednisone response 1, 4
• Adult data: The EORTC ALL-4 trial in adults showed NO advantage for dexamethasone over prednisolone (6-year EFS 25.9% vs 28.7%, P=0.82), suggesting the pediatric benefit may not translate to adults 3

This discrepancy means: In adult ALL (age >40 years), prednisone at 60 mg/m² per day remains a reasonable choice, particularly in hyper-CVAD regimens where dexamethasone is typically used at lower doses 1, 3

Common Pitfalls to Avoid

1. Do not use prednisone when CNS disease is present at diagnosis: These patients require cranial irradiation plus dexamethasone for adequate CNS penetration 1

2. Do not assume dexamethasone is always superior: In precursor B-cell ALL (the majority of cases), the EFS benefit does not translate to OS benefit due to worse salvage outcomes after relapse 4

3. Monitor for myopathy with dexamethasone: Risk is 7.05-fold higher (RR 7.05; 95% CI 3.00-16.58); assess muscle strength regularly 1, 2

4. Taper corticosteroids appropriately: Both agents require tapering after prolonged use to prevent adrenal insufficiency 2

5. Consider combination therapy: Emerging data suggest that combining low-dose dexamethasone (1/50 weight ratio) with prednisolone may overcome prednisolone resistance while minimizing dexamethasone toxicity, though this requires further clinical validation 6