FROM DIAGNOSING ACUTE PROMYELOCYTIC LEUKEMIA TO EXTRACORPOREAL MEMBRANE OXYGENATION IN TWO WEEKS

Abstract

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: We present a patient that developed Differentiation Syndrome (DS) during her second week of induction chemotherapy with all-trans retinoic acid (ATRA). Her case was complicated by influenza A infection with severe acute respiratory distress syndrome (ARDS) that lead to Extracorporeal Membrane Oxygenation (ECMO) and ultimately death. CASE PRESENTATION: A 65 year old woman presented with rapidly progressive thrombocytopenia, palpitations, easy bruising, and epistaxis. Labs were notable for platelets of 21×10ˆ9/L, fibrinogen of 80 mg/dL, and a D-Dimer > 20 ug/mL. Peripheral blood smear showed abnormal promyelocytes suspicious for acute promyelocytic leukemia (APL). Bone marrow biopsy was performed. Given concern for disseminated intravascular coagulopathy (DIC) and APL, therapy was initiated with oral all-trans retinoic acid (ATRA) preceded by prednisone 0.5 mg/kg/day to reduce the risk of DS. Arsenic trioxide (ATO) was added after FISH confirmed PML/RARA t(15;17) translocation, which is diagnostic for APL. The DIC resolved. On hospital day 6, she reported new dry cough. On hospital day 11, she developed shortness of breath, hypoxia and bilateral lower extremity edema. Influenza A PCR resulted positive and CT chest showed patchy bilateral diffuse alveolar opacities. Oseltamivir and Cefepime were initiated. Prednisone was changed to Dexamethasone 10 mg twice daily for possible DS. ATRA and ATO were discontinued. Bronchoalveolar lavage cell count showed 13% neutrophils, with negative bacterial and fungal cultures. The patient's hypoxemia worsened requiring endotracheal intubation. Chest X-ray showed worsening diffuse pulmonary infiltrates. Transthoracic echocardiogram showed no evidence of left ventricular systolic or diastolic dysfunction. In the setting of ARDS, she was placed prone, paralyzed, and received high levels of PEEP. As her oxygenation remained poor, venovenous ECMO was initiated. She was weaned off ECMO five days later, however, experienced worsening of her respiratory status thereafter and the decision was made for palliative ventilator withdrawal. DISCUSSION: DS likely arises as a result of increased release of vasoactive cytokines. DS typically occurs during the first or third week of induction chemotherapy with ATRA and the diagnosis is established clinically. Prompt treatment with at least 3 days of Dexamethasone 10 mg twice daily is the treatment of choice. With adequate treatment, the majority of patients experience improvement, typically within a day. Mortality in DS typically results from hypoxemic respiratory failure. CONCLUSIONS: DS is a life threatening complication of induction chemotherapy in patients with APL. Prompt recognition and early treatment with steroids are essential, but fatal complications such as ARDS may still occur, especially when a second inciting event, such as influenza A infection is present. Reference #1: Montesinos P et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009 Jan 22;113(4):775-83 Reference #2: Tallman MS et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood. 2000 Jan 1;95(1):90-5 Reference #3: Patatanian E et al. Retinoic acid syndrome: a review. J Clin Pharm Ther. 2008 Aug;33(4):331-8 DISCLOSURES: No relevant relationships by Mouhanned Eliliwi, source=Web Response No relevant relationships by Phillip Gary, source=Web Response No relevant relationships by Brian Hirsh, source=Web Response No relevant relationships by Leah Lande, source=Web Response No relevant relationships by Jennifer Meyfeldt, source=Web Response