Three patients had clinical grade ≥3 TLS, manifesting as cardiac arrhythmia (1) and/or renal insufficiency (2), including a patient with AML who developed hyperacute TLS requiring hemodialysis and died of acute renal failure (ARF) on day 13 of cycle 1, despite intense pre-treatment prophylaxis with rasburicase, calcium acetate, and sevelamer and aggressive treatment of TLS with insulin, calcium gluconate, and sodium polystyrene sulfonate. The gene discussed is INS; the disease is Renal insufficiency.