A prospective trial of prophylaxis and treatment (P+T) of acute tumor lysis syndrome (ATLS) with rasburicase (R) and nonalkaline hydration in children and adolescents (C+A) with intermediate- (Group B) and high-risk (Group C) mature B-NHL: A Children's Oncology Group report.

Abstract

9572 Background: The incidence of TLS and renal insufficiency (RI) in our past study in C+A with Group (GP) C B-NHL P+T with allopurinol and alkaline hydration was 26% and 27%, respectively (Cairo, Blood 2007). R is more effective than allopurinol in rapidly reducing hyperuricemia in C+A at high risk of ATLS. (Goldman/Cairo, Blood 2001). Objectives: To assess the toxicity, incidence of ATLS, RI and assisted renal support (ARS) of R added to COP reduction in C+A with GP B + C B-NHL. Methods: COP was administered as previously described (Cairo, Blood, 2007). R (0.2 mg/kg IV) was generously supplied by sanofi-aventis. Hydration (without sodium bicarbonate) was administered at 3 L/m2/day. Laboratory (LTLS) and Clinical (CTLS) were classified according to the Cairo- Bishop classification (BJH, 2004). Chemotherapy began between 4 and 24 hrs of the day 0 R dose. GFR (ml/min/1.73 m2) was calculated using the pediatric Schwartz formula. Results: Seventy-eight pts were evaluated for response to R with COP including GP B pts (Stage III/IV) that were subdivided into normal (NL < 2XULN) (n=23) and high (HI ≥ 2XULN) (n=20) LDH and 35 GP C pts. Mean and elevated (% pts ≥ 8 mg/dl) initial uric acid (UA mg/dl) were 4.5 ± 2 (8.2%), 9.6 ± 4.6 (47%) and 8.6 ± 5.0 (45%), in the three groups, respectively. 47% pts received optional doses of R prior to day 0 and no SAE were attributed to any R doses. Two/20 (10%) in GP B HI LDH and 4/35 (11%) in GP C presented with RI and required ARS prior to R + COP therapy. The incidence of LTLS was 0%, 25% and 17% and CTLS was 0%, 10%, and 11%, respectively. GFR improved from baseline thru day 7 in all three groups: GP B NL LDH (141 ±29 to 154 ± 34), GP B HI LDH (96 ± 40 to 168 ± 45) and GP C (108 ± 42 to 173 ± 64). Conclusions: R during COP reduction is well tolerated and highly effective in preventing and treating ATLS in C+A with FAB group B (stage III/IV) and C B-NHL. Although R added to COP prevents new onset CTLS and need for ARS, approximately 10% of C+A with GP B HI LDH or GP C B-NHL still present at diagnosis with RI and require ARS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis