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. This evidence concerns the gene INS and cardiac rhythm disease.