Assessment of rasburicase utilization for tumor lysis syndrome management in pediatric and adult patients in the inpatient and outpatient settings.

INTRODUCTION: At Wake Forest Baptist Health, an adult tumor lysis syndrome pocket card was created in order to optimize management of tumor lysis syndrome and outline specific recommendations for the use of rasburicase. Due to the increased use of rasburicase at our institution and its cost, the purpose of this study was to evaluate the utilization of rasburicase for the management of tumor lysis syndrome in pediatric and adult patients in the inpatient and outpatient settings. METHODS: This was an observational, single-center, non-randomized, retrospective chart review conducted between September 2018 and August 2019. The primary objective was to evaluate the utilization of rasburicase and appropriateness for the management of tumor lysis syndrome in pediatric and adult patients based on the Wake Forest Baptist Health tumor lysis syndrome pocket card. The secondary objectives were to assess response to prophylactic and treatment doses of rasburicase and to quantify drug cost versus expense of rasburicase utilization. RESULTS: Overall, 64 patients (57 adults and 7 pediatric patients) were included in the study. Rasburicase use for tumor lysis syndrome indication adhered to the pocket card 64% of the time. Appropriate fluids and/or allopurinol were initiated in only 34% of patients. For monitoring, 80% of patients had all necessary tumor lysis syndrome laboratory values collected after rasburicase administration. All 11 patients (17%) who received rasburicase in the outpatient setting did not have follow-up labs collected. Of the patients who had tumor lysis syndrome laboratory values collected post rasburicase, 39% were appropriately timed to accurately assess efficacy of rasburicase with the median time of laboratory monitoring after rasburicase being 6.5 h. Response was observed with rasburicase 3 mg (92%), 6 mg (100%), and weight-based dosing (100%). The wholesale acquisition cost per patient was $5203 (1101-10,406). The potential cost savings of using the 3 mg dose versus the 6 mg dose for the patients who did not meet tumor lysis syndrome treatment recommendations based on the Wake Forest Baptist Health pocket card was estimated to be $36,419.46. CONCLUSION: There are several opportunities for improvement in tumor lysis syndrome management and rasburicase utilization at our institution. This study will lead to the implementation of formal restrictions for rasburicase use and selection of rasburicase dose. Updating the rasburicase order panel to include appropriate prophylaxis and require input of uric acid level, populating pertinent tumor lysis syndrome laboratory values on the order verification screen for pharmacists to appropriately assess if rasburicase meets the institution restriction criteria, and providing education to providers on the appropriate ordering and timing of labs.

Abnormal Skeletal Muscle Regeneration plus Mild Alterations in Mature Fiber Type Specification in Fktn-Deficient Dystroglycanopathy Muscular Dystrophy Mice.

Glycosylated α-dystroglycan provides an essential link between extracellular matrix proteins, like laminin, and the cellular cytoskeleton via the dystrophin-glycoprotein complex. In secondary dystroglycanopathy muscular dystrophy, glycosylation abnormalities disrupt a complex O-mannose glycan necessary for muscle structural integrity and signaling. Fktn-deficient dystroglycanopathy mice develop moderate to severe muscular dystrophy with skeletal muscle developmental and/or regeneration defects. To gain insight into the role of glycosylated α-dystroglycan in these processes, we performed muscle fiber typing in young (2, 4 and 8 week old) and regenerated muscle. In mice with Fktn disruption during skeletal muscle specification (Myf5/Fktn KO), newly regenerated fibers (embryonic myosin heavy chain positive) peaked at 4 weeks old, while total regenerated fibers (centrally nucleated) were highest at 8 weeks old in tibialis anterior (TA) and iliopsoas, indicating peak degeneration/regeneration activity around 4 weeks of age. In contrast, mature fiber type specification at 2, 4 and 8 weeks old was relatively unchanged. Fourteen days after necrotic toxin-induced injury, there was a divergence in muscle fiber types between Myf5/Fktn KO (skeletal-muscle specific) and whole animal knockout induced with tamoxifen post-development (Tam/Fktn KO) despite equivalent time after gene deletion. Notably, Tam/Fktn KO retained higher levels of embryonic myosin heavy chain expression after injury, suggesting a delay or abnormality in differentiation programs. In mature fiber type specification post-injury, there were significant interactions between genotype and toxin parameters for type 1, 2a, and 2x fibers, and a difference between Myf5/Fktn and Tam/Fktn study groups in type 2b fibers. These data suggest that functionally glycosylated α-dystroglycan has a unique role in muscle regeneration and may influence fiber type specification post-injury.