ALL-343 Transient Elastography Is Not a Predictor of Hepatotoxicity in Newly Diagnosed Acute Lymphoblastic Leukemia Patients Undergoing Asparaginase-Based Induction Chemotherapy

Asparaginase-based, pediatric-inspired regimens have improved survival of adolescent and young adults with acute lymphoblastic leukemia (ALL), although hepatotoxicity and metabolic toxicities, more common in adults and in the Hispanic population, often limit treatment. The mechanisms of toxicity are not completely understood, but small preclinical and clinical studies suggest liver steatosis may play a role. Ultrasound transient elastography is a non-invasive diagnostic test used to assess liver stiffness and steatosis, although its ability to predict asparaginase hepatotoxicity is not known. The aim of this study was to prospectively assess patients with newly diagnosed B-ALL or lymphoblastic lymphoma treated with a modified CALGB10403 for steatosis and/or fibrosis using liver transient elastography before the start of chemotherapy, and to correlate these parameters with the occurrence of hepatotoxicity. According to recently published guidelines, steatosis was defined as a CAP ≥ 275 dB/m, and absence of fibrosis as an E < 5 kPa. Forty-two patients were included, 95.2% with a B-ALL diagnosis and the rest with lymphoblastic lymphoma. Median age at diagnosis was 30.5 years (range, 18-49) and 50% were women. Median CAP was 249.5 dB/m (range, 143-380), and median E was 5.85 kPa (range, 3.4-17.5); 33.3% of patients were categorized as having liver steatosis and 26.2% as not having fibrosis. Steatosis was more frequent in patients with diabetes (OR 7.22; 95% CI, 1.18-43.98), age older than 30 years (OR 5.33; 95% CI, 1.20-23.66), or a BMI >25 (OR 6.0; 95% CI, 1.13-31.88). Nineteen patients (45.2%) experienced grade 3 or 4 hepatoxicity during induction chemotherapy. Neither steatosis (53.6% vs 28.6%, P =.191) nor the lack of fibrosis (54.5% vs 41.9%, P =.504) was associated with the occurrence of hepatotoxicity. Median CAP and E values did not differ between patients with and without hepatotoxicity during induction (256 vs 235 dB/m, P =.215, and 5.8 vs 5.9 kPa, P> .99, respectively). Grade 3 or 4 hepatotoxicity occurred in nearly half of patients undergoing asparaginase-based induction chemotherapy, but transient elastography values did not correlate with the incidence of this complication. There is an unmet need in understanding the mechanisms and prevention of asparaginase induced hepatotoxicity.