Evaluation of Low Dose Rasburicase In the Prevention of Renal Insufficiency and Dialysis After Chemotherapy
Authors: Eirin Aflonso , Irazabal Maria V , Gunderson Heidi D , Leung Nelson 
Published: October 2019

Abstract
Abstract 2574
Rasburicase is a recombinant urate oxidase approved for the prevention of tumor lysis syndrome (TLS). In adults, the recommended dose is 0.2 mg/kg intravenously daily up to 5 days. For a 75 kg person, the cost is over $5100. Given the vast reduction of uric acid seen with this dose, it may be possible to use a reduce dose. The aim of this study is to evaluate the effectiveness of 0.1 mg/kg dose vs the recommended dose in the prevention of TLS. Between October of 2003 and February of 2009, all patients with a hematologic or oncologic diagnosis who received rasburicase were reviewed. Rasburicase had been dosed at either 0.1 mg/kg (low dose) or 0.2 mg/kg (standard dose) due to variations in practice among the practitioners. Rasburicase was given on the first day of chemotherapy and repeated as necessary. Renal insufficiency was defined by 0.5 mg/dl rise in serum creatinine (Scr) within 7 days of chemotherapy initiation. The need for dialysis was recorded separately. Labs were performed pretreatment and usually daily after chemotherapy until electrolytes stabilized. A multivariate analysis using pretreatment labs was performed to determine risk factors for renal insufficiency or failure. During the study period, 125 patients received rasburicase. Fifty-five patients received low dose rasburicase and 70 received the standard dose. The diagnoses are listed in Table 1. Lactate dehydrogenase (LDH) was similar between the two groups (604 U/l in low dose vs 665 U/l in standard dose, p = 0.69). Additional doses were required in 14.5% of the low dose patients vs 21.4% of the standard dose patients, p = 0.36. Renal insufficiency was noted only in the standard dose patients 7.4% vs 0%, p = 0.04. Rates of dialysis were similar between low dose patients 7.3% vs 17.4% in the standard dose patients, p = 0.10. Dialysis was often initiated for hyperkalemia and hyperphosphatemia. Only 12.5% were started for elevation in Scr. Uric acid reduction was higher in the standard dose patients (90.4 ± 15.8%) as compared with low dose patients (82.0 ± 19.0%, p = 0.01). Pretreatment Scr, uric acid and phosphorus levels were found to be significant variable for dialysis but only uric acid was found to be significant in the multivariate analysis. Pretreatment uric acid was a risk factor for dialysis (p < 0.001) but not for renal insufficiency (p = 0.24). Our results suggest that low dose rasburicase may be as effective as 0.2 mg/kg. While high dose rasburicase was more effective at reducing uric acid, it did not reduce the need for dialysis because dialysis was often needed for hyperkalemia and hyperphosphatemia which rasburicase did not affect. Despite bias, our results suggest low dose rasburicase may be a viable alternative and definitely support further study into its use. The potential savings could be enormous given that it would be $2550 per patient.
Table 1. Baseline diagnosis of 125 patients with TLS Diagnosis Low dose Standard dose dose Diffuse large B-cell lymphoma 13 17 Chronic lymphocytic leukemia 3 12 Multiple myeloma 7 5 Non-Hodgkin's lymphoma 4 7 Acute myeloid leukemia 4 7 Burkitt's lymphoma 3 4 T-cell lymphoma 4 3 B-cell lymphoma 5 1 Solid Tumor 1 5 Myelofibrosis 3 2 Mantle cell lymphoma 3 1 Amyloidosis 0 2 Blast crisis in acute leukemia 1 1 B-cell lymphoproliferative disorder 0 1 Chronic myeloproliferative disorder 0 1 Follicular mixed lymphoma 0 1 Hodgkin's lymphoma 1 0 undifferentiated 1 0 Lymphoreticular myeloid malignancy 1 0 Post-transplant lymphoproliferative disorder 0 1 Splenic marginal cell lymphoma 1 0 Waldenstrom macroglobulinemia 1 0 Total 55 70

Disclosure:
No relevant conflicts of interest to declare.