Laura Brickett, BCCCP, PharmD
Geisinger Medical Center
Danville, Pennsylvania
Disclosure information not submitted.
Benjamin Andrick, PharmD, BCOP
Hematology/Oncology Clinical Pharmacist
Geisinger Medical Center Danville, United States
Disclosure information not submitted.
Title: Tumor Lysis Syndrome in Critically Ill Patients Receiving Flat-Dose Allopurinol Prophylaxis
Introduction: Allopurinol is used prophylactically in patients with aggressive, chemosensitive tumors to mitigate elevated uric acids levels and the development of tumor lysis syndrome (TLS). Per the package insert, allopurinol is dosed 300 mg/m2/day for this indication, though some institutions have reportedly used a flat-dose strategy of 300 mg daily. Given the higher acuity of ICU patients, they may be more susceptible to electrolyte disturbances, seizures, and arrhythmias. The purpose of this study is to evaluate the effectiveness of allopurinol 300 mg daily in the prevention of TLS in critically ill patients.
Methods: This was a retrospective, single-center cohort study of adult ICU patients receiving allopurinol for TLS prophylaxis from January 2010 to June 2020. Patients were excluded if they received a dose of rasburicase before or within 24 hours of their first allopurinol dose. The primary outcome was the percentage of patients developing TLS, defined by laboratory and clinical parameters or rasburicase use > 24 hours after allopurinol initiation. Secondary outcomes included median dose of allopurinol, development of acute kidney injury (AKI), and need for dialysis.
Results: A total of 103 patients were included for analysis. Patients were generally in their sixth decade of life and predominately Caucasian males. Most patients had a history of leukemia (55%) followed by lymphoma (34%), lung cancer (9%), and multiple myeloma (2%). 40 (39%) patients were considered low risk for TLS, 42 (41%) were at intermediate risk, and 21 (20%) were at high risk at baseline. TLS occurred in 45 (44%) patients with 26 (25%) patients meeting laboratory criteria, 30 (29%) meeting clinical criteria, and 12 (12%) receiving rasburicase. The median daily dose of allopurinol was 300 mg (range 50-300 mg). 26 (25%) patients developed AKI, and 10 (10%) required dialysis.
Conclusions: Clinical and laboratory TLS occurred despite the use of flat-dose allopurinol in patients admitted to the ICU. Further investigation is warranted to optimize the dose of allopurinol in critically ill patients.