Contributions
Abstract: PB1424
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia defined by the translocation t(15;17)(q22;21). All-trans retinoic acid (ATRA) is a cornerstone of treatment for APL. However, ATRA use is associated with a spectrum of severe complications known as differentiation syndrome (DS). With the exception of pericardial effusion, cardiac involvement is extremely rare after ATRA exposure.
Aims
We present a patient who developed myocarditis as an unusual complication after ATRA treatment.
Methods
A 23-year-old female presented with one week history of generalized headache, emesis, and ecchymosis. Lab findings revealed leukocytosis (44.5 x 109/mm3), normocytic anemia (11.3 g/dL), thrombocytopenia (38 000/mm3), hypofibrinogenemia (fibrinogen 64 mg/dL), elevated d-dimer (48 293 ng/mL), and coagulopathy (prothrombin time international normalized ratio 2.0) consistent with disseminated intravascular coagulation. Peripheral blood smear demonstrated 82% blasts with Auer rods, consistent with acute promyelocytic anemia (APL) and later confirmed on bone marrow aspirate and biopsy. PCR for PML-RARA fusion gene was positive. Karyotype was 46,XX,del(9)(q13q22),t(15;17)(q24;q21). On confirmation of the diagnosis, the patient was initiated on ATRA and idarubicin. One day following the first administration of ATRA, the patient began to complain of dyspnea on exertion and chest pain. She developed transient hypoxia (SpO2 90%) and sinus tachycardia.
Results
Troponin I was elevated to 2849 pg/mL, but there were no electrocardiographic changes suggestive of ischemia. Computerized tomography of the chest demonstrated new bilateral interstitial infiltrates and small pleural effusions. Blood and bronchoalveolar lavage microbiology cultures were negative. Echocardiogram was negative for any valvular dysfunction, systolic dysfunction, or wall motion abnormalities. However, cardiac magnetic resonance imaging (MRI) demonstrated delayed focal subepicardial enhancement suggestive of myocarditis. The patient was immediately started on intravenous dexamethasone 10 mg every 12 hours for treatment of both DS and myocarditis, and demonstrated resolution of symptoms as well as normalization of cardiac enzymes. She was advised to continue a prolonged prednisone tapering regimen after completion of dexamethasone for 14 days. Three months after her diagnosis, follow-up echocardiogram demonstrated normal function with a complete resolution of symptoms.
Conclusion
DS is a heterogeneous condition whose pathogenesis and diagnostic criteria remain yet to be clearly defined. This patient meets criteria for possible differentiation syndrome given the presence of dyspnea with interstitial pulmonary infiltrates, as well as a small pericardial effusion, after ATRA induction. Review of existing literature identified 11 other cases of ATRA-induced myocarditis, of which only 2 reported concurrent DS-defining symptoms. All cases demonstrated onset of symptoms within 1 month of ATRA induction. Due to the scarcity of available reports, cardiac complications are an under-recognized sequelae of ATRA use. We postulate that myocarditis although rare, is likely to be a constituent of the amalgam of pathologies involved in DS. Cardiac MRI may be a more accurate non-invasive diagnostic test to confirm myopericarditis after ATRA induction.
Keyword(s): Acute promyelocytic leukemia, Retinoic acid
Abstract: PB1424
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia defined by the translocation t(15;17)(q22;21). All-trans retinoic acid (ATRA) is a cornerstone of treatment for APL. However, ATRA use is associated with a spectrum of severe complications known as differentiation syndrome (DS). With the exception of pericardial effusion, cardiac involvement is extremely rare after ATRA exposure.
Aims
We present a patient who developed myocarditis as an unusual complication after ATRA treatment.
Methods
A 23-year-old female presented with one week history of generalized headache, emesis, and ecchymosis. Lab findings revealed leukocytosis (44.5 x 109/mm3), normocytic anemia (11.3 g/dL), thrombocytopenia (38 000/mm3), hypofibrinogenemia (fibrinogen 64 mg/dL), elevated d-dimer (48 293 ng/mL), and coagulopathy (prothrombin time international normalized ratio 2.0) consistent with disseminated intravascular coagulation. Peripheral blood smear demonstrated 82% blasts with Auer rods, consistent with acute promyelocytic anemia (APL) and later confirmed on bone marrow aspirate and biopsy. PCR for PML-RARA fusion gene was positive. Karyotype was 46,XX,del(9)(q13q22),t(15;17)(q24;q21). On confirmation of the diagnosis, the patient was initiated on ATRA and idarubicin. One day following the first administration of ATRA, the patient began to complain of dyspnea on exertion and chest pain. She developed transient hypoxia (SpO2 90%) and sinus tachycardia.
Results
Troponin I was elevated to 2849 pg/mL, but there were no electrocardiographic changes suggestive of ischemia. Computerized tomography of the chest demonstrated new bilateral interstitial infiltrates and small pleural effusions. Blood and bronchoalveolar lavage microbiology cultures were negative. Echocardiogram was negative for any valvular dysfunction, systolic dysfunction, or wall motion abnormalities. However, cardiac magnetic resonance imaging (MRI) demonstrated delayed focal subepicardial enhancement suggestive of myocarditis. The patient was immediately started on intravenous dexamethasone 10 mg every 12 hours for treatment of both DS and myocarditis, and demonstrated resolution of symptoms as well as normalization of cardiac enzymes. She was advised to continue a prolonged prednisone tapering regimen after completion of dexamethasone for 14 days. Three months after her diagnosis, follow-up echocardiogram demonstrated normal function with a complete resolution of symptoms.
Conclusion
DS is a heterogeneous condition whose pathogenesis and diagnostic criteria remain yet to be clearly defined. This patient meets criteria for possible differentiation syndrome given the presence of dyspnea with interstitial pulmonary infiltrates, as well as a small pericardial effusion, after ATRA induction. Review of existing literature identified 11 other cases of ATRA-induced myocarditis, of which only 2 reported concurrent DS-defining symptoms. All cases demonstrated onset of symptoms within 1 month of ATRA induction. Due to the scarcity of available reports, cardiac complications are an under-recognized sequelae of ATRA use. We postulate that myocarditis although rare, is likely to be a constituent of the amalgam of pathologies involved in DS. Cardiac MRI may be a more accurate non-invasive diagnostic test to confirm myopericarditis after ATRA induction.
Keyword(s): Acute promyelocytic leukemia, Retinoic acid