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3. APL is a medical emergency and treatment should be initiated with all-trans retinoic acid
APL is unique among leukemia’s due to its sensitivity to all-trans retinoic acid (ATRA; tretinoin), the acid form of vitamin A (2). Treatment with ATRA allows induces the terminal differentiation of the leukemic promyelocytes, after which these differentiated malignant cells undergo spontaneous apoptosis on their own. APL is a medical emergency with a high rate of early mortality often due to hemorrhage from coagulopathy. Treatment with ATRA should be initiated as soon as the diagnosis is suspected.
APL accounts for 5-20% of cases of acute myelogenous leukemia with only 600-800 new cases per year in the US. APL is not a rapidly proliferative acute leukemia. The course of the preclinical phase is unclear. Presentation is usually late in the course with life-threatening catastrophic bleeding. Bleeding is caused by degranulation of tissue factor, which leads to disseminated intravascular coagulation (DIC), and release of leukocyte proteases that leads to hypofibrinogenemia. This constitutes a true hematologic emergency that many intensivists will eventually have to recognize and treat. At time of diagnosis the bone marrow is typically replaced by 100% malignant promyelocytes leading to severe anemia, thrombocytopenia and neutropenia. Only a small number of APL cells may be present in the blood.
ATRA alone is capable of inducing remission but it is short-lived in the absence of concurrent "traditional" chemotherapy (2). The standard of treatment for concurrent chemotherapy is arsenic trioxide. Chemotherapy with ATRA and arsenic trioxide results in a clinical remission in approximately 90% of patients. ATRA syndrome or cytokine storm syndrome is a potentially fatal complication of induction chemotherapy for APL (3). It occurs in 25% of patients with APL during induction therapy and is caused by the release inflammatory vasoactive cytokines leading to capillary leak. Symptoms include dyspnea, edema, unexplained fever, hypotension, pulmonary hemorrhage, respiratory failure, renal failure, hepatic failure, and cerebral edema. If suspected, dexamethasone should be initiated while chemotherapy is continued.
The patient was initiated on ATRA chemotherapy and developed improvements in her leg examination along with blood counts within days of starting the therapy (Figure 4).
Figure 4. Before (left) and after (right) pictures. The picture on the right was taken 3 days after ATRA was started.
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