What is the recommended dose of Triretinoin (all-trans retinoic acid) for acute promyelocytic leukemia (APL)?

Tretinoin (ATRA) Dosing for Acute Promyelocytic Leukemia

The recommended dose of tretinoin (all-trans retinoic acid, ATRA) for acute promyelocytic leukemia is 45 mg/m² per day divided into two doses, administered orally and continued daily until complete remission is achieved. 1

Standard Dosing Regimen

• ATRA 45 mg/m² per day in 2 divided doses is the established standard dose across all major guidelines for both induction and consolidation therapy 1, 2, 3
• This dose should be initiated immediately upon clinical suspicion of APL without waiting for genetic confirmation, as early initiation prevents the lethal complication of hemorrhage 1, 2, 3
• Continue ATRA daily until bone marrow remission is documented 1

Risk-Stratified Treatment Approach

Low/Intermediate Risk (WBC ≤10,000/mcL)

• ATRA 45 mg/m² in 2 divided doses daily combined with either:
  • Arsenic trioxide 0.15 mg/kg IV daily 1, 2, 3, OR
  • Daunorubicin 50-60 mg/m² for 3-4 days + cytarabine 200 mg/m² for 7 days 1, 2, 3, OR
  • Idarubicin 12 mg/m² on days 2,4,6,8 1, 2, 3

High Risk (WBC >10,000/mcL)

• ATRA 45 mg/m² in 2 divided doses daily plus an anthracycline-based regimen 1, 2
• Consider prophylactic dexamethasone to prevent differentiation syndrome 1, 2

Special Population Considerations

Adolescents and young adults may receive lower doses of ATRA (25 mg/m²), though this is less well-established 1, 2, 4

• One study demonstrated that doses as low as 15-25 mg/m²/day remain effective, though 45 mg/m² remains the guideline-recommended standard 4
• Therapy-related APL is treated identically to de novo APL with the same ATRA dosing 1, 2

Critical Management Points

Immediate Initiation

• Start ATRA on first clinical suspicion based on morphology showing hypergranular or microgranular promyelocytes, even before t(15;17) confirmation 1, 2, 3
• If genetic testing does not confirm APL, discontinue ATRA and treat as conventional AML 1, 2, 3

Monitoring Requirements

• Monitor continuously for differentiation syndrome and coagulopathy throughout induction 1, 2, 3
• Maintain platelets ≥30-50 × 10⁹/L and fibrinogen 100-150 mg/dL until coagulopathy resolves 2
• Do not perform premature bone marrow assessment at days 10-14 as it is misleading; patients often remain molecularly positive despite morphologic remission 1, 2, 3

Common Pitfalls to Avoid

• Never mix induction from one protocol with consolidation from another—use a consistent regimen throughout all treatment phases 1, 2
• Do not delay ATRA initiation waiting for cytogenetic confirmation, as early hemorrhagic death is the primary cause of treatment failure 1, 2, 3
• The first molecular remission assessment should only be performed after consolidation therapy is complete 1, 2, 3

Adverse Effects Management

Common side effects at the 45 mg/m² dose include skin and mucosa dryness, hypertriglyceridemia, and elevated hepatic transaminases 5

• Bone pain occurs in approximately 50% of patients 5
• Differentiation syndrome (formerly called retinoic acid syndrome) occurs in 8-25% and responds to dexamethasone 6, 5
• If hepatotoxicity develops (bilirubin >3× ULN, AST >5× ULN, or alkaline phosphatase >5× ULN), temporarily discontinue and reinitiate at 50% dose when liver function improves 2

Duration of Therapy

• Continue ATRA during induction until complete remission is achieved 1, 5
• During consolidation, ATRA is typically given for 2 weeks every 4-8 weeks for multiple cycles depending on the specific protocol 1
• Maintenance therapy may include ATRA 45 mg/m² for 2 weeks every 3 months in some protocols 6