AML-278: Examination of Optimal Administration of Arsenic Trioxide in Continuous Renal Replacement Therapy During Acute Promyelocytic Leukemia Treatment

Abstract

<h3>Background and Aim:</h3> Arsenic trioxide (ATO), a safe and effective treatment for acute promyelocytic leukemia (APL), has an effective plasma arsenic concentration (PAC) of 37.6–150 ng/mL. According to current recommendations, the ATO dosage should be reduced for patients receiving intermittent hemodialysis. However, there are no reports on proper ATO administration in patients receiving continuous renal replacement therapy (CRRT); the PAC during CRRT is unknown, and the optimal dosage for patients on CRRT has not been established. We evaluated the appropriate ATO dosage for patients on CRRT. <h3>Patients and Methods:</h3> We enrolled two APL patients undergoing CRRT during ATO therapy. We measured PAC over time to determine the optimal timing of administration required to achieve the therapeutic range for ATO. <h3>Results:</h3> Prior to APL treatment, both patients had normal renal function. The first case was a woman in her 30s with a recurrence of APL. She developed acute kidney injury owing to severe differentiation syndrome and disseminated intravascular coagulation, and she suffered from uncontrolled uremia and fluid volume. Thus, continuous hemodialysis (CHD) was initiated. Because of previous therapy, her PAC was 68 ng/mL at the start of CHD. We administered ATO (0.15 mg/kg) 18 hours after the start of CHD. Her PAC before ATO administration was 60 ng/mL. Immediately after ATO administration, her PAC was 80 ng/mL. However, owing to the redistribution of arsenic, the PAC gradually rose to 100 ng/mL. The second case was a male patient in his 30s who had untreated APL. He also developed acute kidney injury owing to differentiation syndrome. He initially received dialysis but soon required CHD. We administered ATO (0.15 mg/kg) before initiating CHD and at 13 and 39 hours after the start of CHD. His PAC was 110 ng/mL immediately prior to CHD; thereafter, ATO was administered, and his PAC ranged between 130 and 190 ng/mL. At 117 hours after the start of CHD, his PAC was 114 ng/mL, which was within the optimal range. <h3>Conclusions:</h3> PACs exceeded the effective range, even in the presence of CHD. Therefore, we suggest that patients undergoing CHD receive ATO every 48 to 72 hours.