Thrombotic Microangiopathy Due to Liposomal Daunorubicin/Cytarabine

Introduction: Thrombotic Microangiopathy (TMA) is a syndrome defined by microangiopathic hemolytic anemia, thrombocytopenia and end organ damage. With the rise of new chemotherapy regimens, drug induced TMA (DITMA) represents an important and growing cause of TMA. While DITMA has been occasionally reported with conventional daunorubicin/cytarabine we present the first case report of liposomal daunorubicin/cytarabine (lipo-dau/cyt) as a cause of TMA and Acute Kidney Injury (AKI). Case Description: A 70F was admitted for management of Acute Myeloid Leukemia with lipo-dau/cyt. Patient with PMHx of well controlled HTN and Stage 2 carcinoma of left breast s/p bilateral mastectomy and adjuvant chemotherapy. One month after initiating lipo-dau/cyt, creatinine (Cr) rose from 0.94 to 1.68 with peak Cr 2.2. Patient reported worsening lower extremity edema and denied any skin rashes, lesions, or hematuria. Vitals showed worsening HTN with BP 165/107 despite previously being well controlled on outpatient antihypertensives, along with 14lb weight gain. Exam showed new 3mm pitting edema bilaterally to the knees. Labs showed Plt 8, Hgb 6.4, LDH 800, AST 52, ALT 37, UA with new 3+ proteinuria and 1+ urobilinogen. A 24h urine showed 4.9gm proteinuria. Complement activity Sc5-9: 633 ng/ml (h), haptoglobin was <10, ADAM-TS13 normal (74), and other serologic workup negative (SSA/SSB, ANA, ANCA, Anti-Sm, PLA2R, Shiga Toxin, SPEP). A peripheral smear showed numerous schistocytes. A kidney biopsy was performed which showed TMA with acute tubular injury. Lipo-dau/cyt was discontinued. Two months post withdrawal of medication Cr improved to 1.3 and LDH, platelets and haptoglobin normalized. Discussion: This case illustrates the potential for liposomal daunorubicin/cytarabine to cause drug induced TMA. While older non-liposomal formulations have been associated with TMA in the past, this would be first report of its occurrence with the liposomal formulation. Early recognition of liposomal dauno/cyta-associated TMA is important for treatment modification and to help preserve kidney function.