From the Guidelines
The syndrome associated with Acute Promyelocytic Leukemia (APL) treatment with All-Trans Retinoic Acid (ATRA) is APL differentiation syndrome.
Characteristics of APL Differentiation Syndrome
- The syndrome is characterized by symptoms such as dyspnea, unexplained fever, weight gain, peripheral edema, unexplained hypotension, acute renal failure, or congestive heart failure 1
- It can also be identified by a chest radiograph demonstrating interstitial pulmonary infiltrates or pleuropericardial effusion 1
Management of APL Differentiation Syndrome
- Dexamethasone at a dose of 10 mg twice daily by intravenous injection should be started promptly at the earliest symptom or sign of the syndrome 1
- Temporary discontinuation of ATRA or ATO is indicated only in case of severe APL differentiation syndrome 1
- Prophylactic steroids can be given to reduce the risk of APL differentiation syndrome 1
Prevention and Treatment
- The use of ATRA in combination with chemotherapy decreases the incidence of the APL differentiation syndrome in patients with high WBC counts 1
- A dose of 25 mg/m2 per day ATRA appears to produce outcomes equal to the higher dose of 45 mg/m2 per day commonly used in adults with a better safety profile in children 1
From the FDA Drug Label
• Differentiation Syndrome, which can be life-threatening or fatal, occurred in about 26% of patients with APL who received tretinoin. The syndrome associated with Acute Promyelocytic Leukemia (APL) treatment with All-Trans Retinoic Acid (ATRA) is Differentiation Syndrome 2.
- This syndrome can be life-threatening or fatal.
- It occurs in about 26% of patients with APL who receive tretinoin.
From the Research
Syndrome Associated with APL Treatment
The syndrome associated with Acute Promyelocytic Leukemia (APL) treatment with All-Trans Retinoic Acid (ATRA) is known as Differentiation Syndrome (DS) 3, 4, 5, 6, 7.
Characteristics of Differentiation Syndrome
DS is characterized by:
- Weight gain
- Fever not attributable to infection
- Respiratory distress
- Cardiac involvement
- Hypotension
- Acute renal failure 3, 4, 7
- Hyperleukocytosis and cardiorespiratory compromise 6
- Pulmonary infiltrates or pleural or pericardial effusion on chest radiograph 7
Pathogenesis and Treatment
The pathogenesis of DS is not completely understood, but it is believed that an excessive inflammatory response is the main phenomenon involved, resulting in increased production of chemokines and expression of adhesion molecules on APL cells 3. Treatment of DS typically involves:
- Dexamethasone, with a recommended dose of 10 mg twice daily by intravenous route until resolution of DS 3, 4
- Discontinuation of ATRA or ATO in severe cases or if there is no response to treatment 3, 7
- Steroid prophylaxis may be beneficial in preventing DS, particularly in patients with a high white blood cell count at diagnosis 5, 6