From the Guidelines
Acute Promyelocytic Leukemia (APL) is a subtype of acute myeloid leukemia that requires immediate treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) to prevent lethal complications such as bleeding and differentiation syndrome. The disease is characterized by the accumulation of immature granulocytes called promyelocytes in the bone marrow and blood, leading to coagulopathy and increased risk of bleeding 1. Key features of APL include:
- Clinical and pathologic features that necessitate immediate initiation of ATRA upon suspicion of the disease, without waiting for genetic confirmation 1
- High risk of fatal bleeding due to coagulopathy, which can be prevented by early initiation of ATRA 1
- Monitoring for APL differentiation syndrome and disseminated intravascular coagulation (DIC) is crucial 1 Treatment options for APL include:
- ATRA and arsenic trioxide (ATO) for low-to-intermediate risk disease 1
- ATRA plus chemotherapy for high-risk disease 1 The standard regimen for low-to-intermediate risk patients is ATRA 45 mg/m² daily divided into two doses plus ATO 0.15 mg/kg IV daily until complete remission, followed by consolidation therapy. Supportive care with platelets and fibrinogen replacement is essential to maintain counts above 30,000-50,000/μL and prevent bleeding complications 1. Patients must be monitored for differentiation syndrome, a potentially life-threatening complication treated with dexamethasone 10 mg IV twice daily 1. With modern therapy, APL has an excellent prognosis, with cure rates exceeding 90% when treated promptly and appropriately 1.
From the FDA Drug Label
Patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide injection have experienced symptoms of differentiation syndrome, which can be fatal if not treated Arsenic trioxide injection is indicated for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Acute Promyelocytic Leukemia (APL) is a type of leukemia that is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. It is a condition for which arsenic trioxide injection is indicated for treatment. 2
From the Research
Definition and Characteristics of Acute Promyelocytic Leukemia (APL)
- APL is a type of leukemia characterized by a block in differentiation where leukemic cells are halted at the promyelocyte stage 3.
- It is often associated with a balanced chromosomal translocation between chromosomes 15 and 17, resulting in the formation of the PML-RARA fusion protein 3.
- The presence of the PML-RARA fusion transcript is a hallmark of APL and a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapy 4.
Treatment and Management of APL
- ATRA-based induction therapy followed by consolidation chemotherapy has made APL a curable disease, with around 90% of newly diagnosed patients achieving complete remission (CR) and over 70% of patients being curable 5.
- The combination of ATRA and ATO has excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse 4, 6.
- However, the use of ATRA and ATO is associated with a spectrum of distinctive toxicities, such as differentiation syndrome, liver toxicity, QT interval prolongation, and neurotoxicity, which require rigorous monitoring and management 4, 7.
Prognosis and Relapse
- The probability of relapse is significantly higher in the high-risk subset of patients undergoing treatment for APL, with approximately 10-20% of APL patients relapsing regardless of their risk stratification 3.
- Patients who become resistant to ATO have an increased risk of mortality, and alternative agents and approaches are needed to address ATO resistance as well as the relapse rate in high-risk APL 3.