Effectiveness of a Single 3 Mg Rasburicase Dose for the Management of Hyperuricemia in Patients with Hematologic Malignancies.

Abstract

2479 Poster Board II-456 Hyperuricemia(HU) is a frequent complication following therapy for hematologolical malignancies(HM). Conventional therpy with alkalinization, hydration and allopurinol may not be sufficient to lower pre-existingly high uric acid levels(UA). Rasburicase, recombinant urate oxidase, when given at pediatric doses(0.15-.2mg/kg/d x 3-5d)is very effective in lowering UA levels <2mg/dl. The high cost and questionable need to lower UA to near undectectable levels prompted a pre-emptive dose reduced strategy to lower UA. Rasburicase was administered at a single fixed dose of 3 mg to treat 287 episodes of elevated serum UA (>7 mg/dL) in 247 adult patients with hematologic malignancies. 28% had renal failure (serum creatinine >2.5 mg/dL) and 29% had tumor lysis syndrome. The median dose of 36 μg/kg (range 18-65) was a fraction of the recommended pediatric dose of 0.75-1.0 mg/kg over 5 days. The median change in the uric acid levels at 24 hours was -4.1 mg/dL (range -12 to +1) and -45% (range -95 to +9). The uric acid levels normalized at 24 hours in 78% of patients. There was no relationship between the weight-adjusted dose and uric acid decline. The only predictor of resolution of hyperuricemia was baseline uric acid; the failure rate was 84% with baseline uric acid of >12 mg/dL compared to 18% if the baseline level was '12. The level continued to decline beyond 24 hours in the majority of patients in the absence of additional doses. Serum creatinine remained stable over 24 hours and declined over 48 hours and 7 days. There was no relationship between the extent of reduction in uric acid levels and serum creatinine. The approach We conclude that a single 3 mg dose of rasburicase, used with close clinical and laboratory monitoring, is sufficient in most adults with elevated serum uric acid levels up to 12 mg/dL. The best approach to patients with higher levels remains unclear. Table 2: Serum uric acid and creatinine levels and changes (median, range) Serum uric acid (Median, range) Baseline level (mg/dL) 9.3 (7.1–27.3) 24-hour level (mg/dL) 5.3 (0.5–23.0) 24-hour direction of change Any increase 9 (3%) No change 1 (<1%) Any decrease 277 (97%) Increase or <10% decrease 21 (7%) ≥10% decrease 266 (93%) 24-hour absolute change (mg/dL) −4.1 (−12 to +1) 24-hour per cent change (%) −45 (−95 to +9) 24-hour level >7 mg/dL 81 (28%) 24-hour level >5 mg/dL 150 (52%) Serum creatinine (Median, range) Baseline level (mg/dL) 1.7 (0.6–9.7) 24-hour level (mg/dL) 1.6 (0.6–8.7) 24-hour direction of change Any increase 88 (31%) No change 54 (19%) Any decrease 145 (50%) ≥10% increase 52 (18%) <10% change 143 (50%) ≥10% decrease 92 (32%) 24-hour absolute change (mg/dL) −0.1 (−3.3 to +1.4) 24-hour per cent change (%) −3 (−80 to +70) Serum uric acid (mg/dL) 24/7 failure P 24/5 failure P ≤10 13% <0.0001 38% <0.0001 >10 64% 85% ≤12 18% <0.0001 45% <0.0001 >12 84% 93% ≤15 25% <0.0001 50% <0.0001 >15 79% 89% Disclosures: No relevant conflicts of interest to declare.

Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology

“…Only six patients required a second dose and there were no significant renal complications in any patient. More recently, this group have published their experience in a larger cohort of 247 adult patients (Trifilio et al , ). Overall 51/247 patients were treated with a second dose of rasburicase.…”

Tumour lysis syndrome: new territory for a familiar foe?

“…A single dose is sufficient in the majority of adult patients, but close monitoring of biochemical parameters is essential to identify those for whom repeated doses are warranted. This recommendation reflects an 80% dose reduction and is based on a randomized trial and meta‐analysis showing that a lower dose of rasburicase is sufficient to prevent laboratory and thus clinical TLS in the majority of high risk patients (Trifilio et al , ; Coutsouvelis et al , ).…”