Due to a rapid reduction in tumor volume, TLS is an important identified risk when initiating venetoclax. The risk of TLS is reduced with stratification by tumor burden, prophylaxis with hydration and anti-hyperuricemics, frequent blood chemistry monitoring and correction of electrolyte abnormalities. In patients with higher risk features, hospitalization for IV hydration, electrolyte monitoring, and aggressive correction of electrolyte abnormalities may be required. In 66 patients with CLL starting with a daily dose of 20 mg and increasing over 5 weeks to a daily dose of 400 mg, the rate of TLS was 6% with no clinical events. All events were laboratory TLS and occurred in patients who had a lymph node(s) greater than or equal to 5 cm or ALC greater than or equal to 25 x 109/L.