From the Guidelines
ATRA (all-trans retinoic acid) is the primary treatment for acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, and should be initiated as soon as possible, ideally in combination with arsenic trioxide (ATO) for low-to-intermediate risk patients or with chemotherapy for high-risk patients, as this approach has been shown to achieve excellent outcomes and high cure rates 1.
Treatment Approach
The standard treatment approach involves ATRA at a dose of 45 mg/m² daily, divided into two doses. Treatment typically continues until complete remission is achieved, usually 1-3 months, followed by consolidation therapy.
Mechanism of Action
ATRA works by binding to the abnormal PML-RARA fusion protein, causing leukemic promyelocytes to differentiate into mature granulocytes and ultimately undergo apoptosis.
Monitoring and Side Effects
Patients should be monitored for differentiation syndrome, a potentially life-threatening complication characterized by fever, weight gain, respiratory distress, and fluid retention, which requires prompt corticosteroid treatment, such as prednisolone 0.5 mg/kg/day 1. Other side effects include headache, dry skin, bone pain, and elevated liver enzymes. Regular blood counts and liver function tests are essential during treatment.
Key Considerations
- To prevent differentiation syndrome, patients should be treated prophylactically with steroids as soon as they receive ATRA 1.
- Bleeding is the most frequent cause of early death in APL patients, and adequate support is recommended with fibrinogen or fresh-frozen plasma and platelets to maintain levels above 1.0-1.5 g/l and >30-50 × 10^9/l, respectively 1.
- MRD assessment in APL patients should not be made before 4-5 weeks after induction, and should be made after consolidation 1.
From the Research
Atra for Leukemia
- The use of all-trans-retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL) is a standard of care 2, 3, 4, 5, 6.
- ATRA is often used in combination with arsenic trioxide (ATO) and other agents such as daunorubicin or gemtuzumab ozogamicin to treat APL 2, 3, 4.
- The combination of ATRA and ATO has been shown to be effective and safe in treating APL, with high complete remission rates and low toxicity 3, 4.
- The optimal dose and schedule of ATRA and ATO are still being studied, with different regimens being used in different clinical trials 2, 3, 4, 6.
- ATRA-based treatment regimens have been shown to improve outcomes in patients with APL, including high-risk patients 2, 3, 4.
- The use of ATRA and ATO has reduced the need for traditional cytotoxic chemotherapy in the treatment of APL, making treatment more tolerable for patients 3, 4, 6.
Treatment Outcomes
- Complete remission rates of 92-96% have been reported with ATRA and ATO-based regimens 3, 4.
- Overall survival rates of 85-88% have been reported with ATRA and ATO-based regimens 3, 4.
- Relapse rates are low, with 3-7 relapses reported in clinical trials 3, 4.
- Treatment-related mortality is low, with 4-7 deaths reported in clinical trials 3, 4.
Clinical Guidelines
- Clinical guidelines recommend the use of ATRA and ATO in the treatment of APL, with or without other agents such as daunorubicin or gemtuzumab ozogamicin 5, 6.
- The optimal treatment regimen and dose schedule may vary depending on the patient's risk category and other factors 6.
- Maintenance therapy after consolidation is still being studied, with some clinical trials showing benefit and others showing no benefit 5, 6.