Ten-Day Decitabine Treatment in AML Associated with Reversible Non-Ischemic Cardiomyopathy

Abstract Decitabine (5-aza-2'-deoxycytidine), a DNA methyltransferase inhibitor, is used to treat patients with IPSS intermediate 1 or higher Myelodysplastic Syndrome (MDS) and elderly patients with Acute Myeloid Leukemia (AML) not able to receive standard treatment (Blum et al., 2010). Decitabine induced non ischemic cardiomyopathy (NICM) has not been observed in large trials, however, isolated cases of reversible cardiomyopathy have been published (De C et al., 2012). We present two cases of NICM resulting from ten-day course of decitabine treatment for AML; one of which had improved cardiac function with aggressive cardiac management and reduced five-day decitabine course. Case 1 A 69 year old African American male with history of hypertension presented with fatigue and thrombocytopenia (platelet 18k/uL). Bone marrow biopsy showed MDS. Treatment was delayed by 2 months due to lack of insurance and he had worsening cytopenias. Repeat bone marrow biopsy showed AML transformation from MDS (60% myeloblasts). FISH revealed deletion 7 and deletion 5. Echocardiogram (echo) done prior treatment showed borderline concentric left ventricular hypertrophy with ejection fraction (EF) of 55%. Treatment was initiated with Decitabine 20mg/m2 ten-day course every twenty-eight days. On cycle 2 day 23, patient presented with lower extremity edema, and fatigue. Repeat echo revealed severe reduced left ventricular ejection fraction (LVEF) 30% and moderate mitral regurgitation. EKG did not reveal ischemia. Troponin was 0.100ng/mL and NT-proBNP was raised at 14,609pg/mL. Cardiac MRI with and without contrast revealed ventricular dysfunction but did not show myocarditis or myocardial infarction. Bone marrow biopsy at the end of cycle two showed remission with underlying MDS changes. Treatment was switched to Azacitidine 75mg/m2 for 5 days. Repeat echo to reassess is pending at the time of this report. Case 2 62 year old African American female with history of alcohol abuse presented with pancytopenia (WBC 2.7/uL, Hb 9.1g/dl, platelets 35/uL). Bone marrow biopsy revealed 30% myeloblasts, dyspoetic megakaryocytes and 15% ringed sideroblasts. Cytogenetics were complex including deletion 7. Molecular testing was negative for FLT3, NPM and CEBPA mutations. Echo showed EF of 60% with diastolic dysfunction. Decitabine 20mg/m2 x 10 days was given for two cycles. She presented with increasing fatigue and dyspnea on day 15 of cycle 2. Physical exam showed jugular venous distention and peripheral edema. NT-proBNP was markedly elevated at 78,705(pg/mL) and troponin I was 0.254 ng/mL. EKG did not reveal ischemia. Echo demonstrated severely reduced LVEF to Conclusion Cardiac dysfunction caused by permanent myocardial cell injury is a serious side effect of conventional chemotherapies including anthracyclines and antimetabolites. We report two cases of ten-day decitabine regimen causing severe LV systolic dysfunction that were treated with heart failure therapy. Reversal of cardiac complications were seen despite continued therapy with shorter course decitabine suggest that this may be a toxicity of the extended ten-day treatment. Disclosures No relevant conflicts of interest to declare.