What is the treatment regimen for Acute Lymphoblastic Leukemia (ALL) patients using mercaptopurine and dexamethasone?

Mercaptopurine and Dexamethasone for ALL: Patient Counseling

For ALL patients, mercaptopurine is administered at 1.5-2.5 mg/kg orally once daily (or 37.5-50 mg/m² nightly) during maintenance therapy, combined with weekly oral methotrexate, monthly vincristine pulses, and dexamethasone 4-6 mg/m² daily for 5 days every 4 weeks, continuing for approximately 2 years total from diagnosis. 1, 2, 3

Treatment Phases and Drug Roles

Induction Phase

• Dexamethasone is used during induction at 6 mg/m² daily for 28 days (with taper) as part of the multi-drug backbone that includes vincristine, anthracyclines, and L-asparaginase 3
• Dexamethasone provides superior CNS penetration compared to prednisone, reducing isolated CNS relapse risk (3.7% vs 7.1%, p=0.01) and improving 6-year event-free survival (85% vs 77%, p=0.002) 3, 4
• Mercaptopurine may be included during induction primarily for CNS prophylaxis, though its main role is in later phases 3

Consolidation Phase

• Mercaptopurine is administered at 37.5-50 mg/m² nightly for 14 days during consolidation cycles 3
• High-dose methotrexate and cytarabine are the primary consolidation agents 3

Maintenance Phase (Primary Role of Both Drugs)

• Mercaptopurine: 37.5-50 mg/m² (or 1.5-2.5 mg/kg) orally once daily, taken nightly for 28 days per cycle 3, 2
• Oral methotrexate: 15-20 mg/m² weekly 3
• Dexamethasone pulses: 4-6 mg/m² daily for 5 days on week 3 of each 4-week cycle 3
• Vincristine: 1.5 mg/m² (maximum 2 mg) on week 3 of each cycle 3
• Maintenance continues until 2 years from diagnosis (109 weeks total) 3, 5

Critical Counseling Points for Mercaptopurine

Administration

• Take mercaptopurine consistently either with or without food each time—do not alternate 2
• Take at the same time daily, preferably at night 3
• Swallow tablets whole; do not crush or break 2
• If a dose is missed, skip it and continue with the next scheduled dose—do not double up 2

Monitoring Requirements

• Complete blood counts must be monitored regularly to adjust dosing for maintaining adequate absolute neutrophil count 2
• Patients with severe or repeated myelosuppression should be tested for TPMT and NUDT15 deficiency 2
• Patients with homozygous TPMT or NUDT15 deficiency typically require only 10% of the standard dose 2
• Patients with heterozygous deficiency may require dose reductions based on tolerability 2

Drug Interactions

• Allopurinol: If prescribed concurrently, mercaptopurine dose must be reduced to one-third to one-quarter of the current dose to prevent life-threatening toxicity 2
• Warfarin: Mercaptopurine may decrease anticoagulant effect; monitor INR closely 2

Toxicities to Report Immediately

• Myelosuppression: Fever, unusual bruising/bleeding, severe fatigue, or signs of infection 2
• Hepatotoxicity: Jaundice, dark urine, right upper quadrant pain, or persistent nausea 2
• Macrophage activation syndrome: Persistent high fever, hepatosplenomegaly, cytopenias 2

Critical Counseling Points for Dexamethasone

Benefits vs. Risks Trade-off

• Dexamethasone reduces CNS relapse by 47% (RR 0.53,95% CI 0.44-0.65) and improves event-free survival (RR 0.80,95% CI 0.68-0.94) compared to prednisone 3
• However, dexamethasone carries significantly higher risks: induction mortality (RR 2.31,95% CI 1.46-3.66), neuropsychiatric events (RR 4.55,95% CI 2.45-8.46), and myopathy (RR 7.05,95% CI 3.00-16.58) 3
• No overall survival advantage has been conclusively demonstrated (RR 0.91,95% CI 0.76-1.09) 3

Infection Risk During Maintenance

• Repeated, prolonged dexamethasone exposure during maintenance increases risk of lethal infections from 0% to 1.37% (p=0.013) 6
• Seven of 510 children died from severe infections during maintenance with dexamethasone pulses, compared to zero deaths in protocols without dexamethasone pulses 6
• Patients must report fever, chills, or any signs of infection immediately during and shortly after dexamethasone pulses 6

Common Side Effects

• Mood changes: Irritability, anxiety, insomnia, or behavioral changes 3
• Increased appetite and weight gain 3
• Hyperglycemia: Monitor blood glucose, especially in at-risk patients 3
• Osteonecrosis: Report persistent bone/joint pain, particularly in hips or knees 3
• Myopathy: Report muscle weakness or difficulty climbing stairs 3

Administration

• Take dexamethasone with food to minimize gastrointestinal upset 3
• Do not stop dexamethasone abruptly after prolonged use; taper as directed 3

Special Populations

Renal Impairment

• Use the lowest recommended starting dose of mercaptopurine (1.5 mg/kg) in patients with creatinine clearance <50 mL/min 2
• Adjust based on blood counts and tolerability 2

Hepatic Impairment

• Use the lowest recommended starting dose of mercaptopurine and monitor liver function tests closely 2
• Withhold mercaptopurine at onset of hepatotoxicity 2

Reproductive Considerations

• Both drugs can cause fetal harm; effective contraception is mandatory during treatment 2
• Do not breastfeed while taking mercaptopurine 2
• Both drugs can impair fertility in males and females 2

Common Pitfalls to Avoid

• Never co-administer full-dose mercaptopurine with allopurinol without dose reduction—this is a potentially fatal error 2
• Do not ignore persistent fever during dexamethasone pulses; this requires immediate evaluation given the 1.37% risk of lethal infection 6
• Do not delay genetic testing (TPMT/NUDT15) in patients with severe or repeated myelosuppression—these patients may need only 10% of standard mercaptopurine dosing 2
• Do not assume all corticosteroids are equivalent—dexamethasone has distinct pharmacokinetics with better CNS penetration but higher toxicity than prednisone 3