Acute promyelocytic leukemia medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Medical Therapy
APL is unique among the leukemias distinguished by its sensitivity to all-trans retinoic acid (ATRA), a derivative of vitamin A. Treatment with ATRA causes differentiation of the immature leukemic promyelocytes into mature granulocytes. ATRA is typically combined with anthracycline based chemotherapy resulting in a clinical remission in approximately 90% of patients.
ATRA therapy is associated with the unique side effect of retinoic acid syndrome. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.
Treatment options for patients with relapsed disease include arsenic trioxide and allogeneic stem cell transplant. Monitoring for relapse using PCR tests for RARα allows early re-treatment which is successful in many instances.
Anti-leukemic Therapies
- All-trans retinoic acid: The introduction of all-trans retinoic acid has revolutionized the treatment paradigm and outcomes in acute promyelocytic leukemia. The 5-year mortality has decreased from 82% to 36% since the introduction of all-trans retinoic acid.[1]
- Dosing: 45mg/m2 PO daily (typically 22.5mg/m2 PO divided twice daily)
- Adverse effects: The most unique adverse effect of all-trans retinoic acid is differentiation syndrome. This is characterized by weight gain, edema, hypoxia, dyspnea, and pulmonary infiltrates.
- Arsenic trioxide:
- Dosing: 0.15mg/kg IV daily
- Adverse effects: The adverse effects of arsenic trioxide include myelosuppression, liver dysfunction, QT interval prolongation, liver dysfunction.[2]
- Gemtuzumab ozogamycin: This is an anti-CD33 antibody conjugated to the anti-tumor antibiotic calicheamicin. Gemtuzumab ozogamycin is FDA-approved for the treatment of patients with newly diagnosed acute myeloid leukemia expressing the CD33 antigen. Gemtuzumab ozogamycin shows efficacy in acute promyelocytic leukemia. This medication was originally approved in the year 2000 for relapsed acute myeloid leukemia, then was withdrawn from the marker a few years later, then re-introduced to the marker in 2017.
- Adverse effects: The most unique adverse effect is hepatic venoocclusive disease, which is due to the ozogamycin component.
Supportive Therapies
References
- ↑ Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E; et al. (2017). "Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab". Blood. 129 (10): 1275–1283. doi:10.1182/blood-2016-09-736686. PMC 5413297. PMID 28003274.
- ↑ McCulloch D, Brown C, Iland H (2017). "Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives". Onco Targets Ther. 10: 1585–1601. doi:10.2147/OTT.S100513. PMC 5359123. PMID 28352191.