Risk assessment and medical decision model for prophylaxis and treatment of hyperuricemia and tumor lysis syndrome (TLS): International expert panel analysis

17006 Background: Hyperuricemia, a major component of TLS, has historically been prevented and treated using allopurinol and alkalinization, and recently managed effectively by rasburicase (recombinant urate oxidase) in children and adults at high risk of TLS. We sought to determine the risk factors associated with TLS and develop a risk adapted medical decision model for the prevention and treatment of hyperuricemia in TLS. Methods: TLS risk scoring was performed by an expert panel, based on an odds ratio evaluation of 68 patient characteristics and cancers with known TLS risk. The RAND Appropriateness Method (RAM) (1–3 inappropriate, 4–6 uncertain, 7–9 appropriate) was utilized to investigate the appropriateness of prevention and treatment in 92 different scenarios. All appropriateness ratios were validated using a set of 36 clinical cases. The strategies analyzed included no therapy, hydration (± diuretics [DI]), rasburicase, allopurinol, and allopurinol + alkalinization. Results: Risk factors (±SD) identified included age ≥ 60 years (1.6±0.5), decreased renal function (2.7±1.1), renal tumor infiltration (1.5±0.3), initial cytoreductive therapy (2.5±1.2), acute lymphoblastic leukemia with WBC ≥50x109/L [Burkitt 8.6±5.3; pre-B 4.3±2.4; T-cell 4.6±2.8]; and non-Hodgkin lymphoma with LDH≥ 2x normal [Burkitt 6.6±3.0; lymphoblastic 3.2±2.8; diffuse large B-cell 2.4±1.9]. Hydration (± DI) was considered appropriate while no treatment and allopurinol + alkalinization were inappropriate in all scenarios. For prophylaxis, rasburicase was more appropriate than allopurinol (8.5±0.5 vs 4.9±2.1; p<0.025) in patients with hyperuricemia and/or at high risk of TLS, whereas allopurinol was more appropriate than rasburicase (6.2±1.0 vs 4.9±1.9; p<0.05) in those at low or moderate risk. In patients with TLS and normal urine output and uric acid, allopurinol and rasburicase were considered equally appropriate (5.0±0.9 vs 5.8±0.3). Conclusions: In summary, in addition to hydration (± DI), rasburicase is appropriate for patients at high risk of TLS and/or with hyperuricemia, and allopurinol for those with low risk of TLS and/or normal uric acid concentration. [Table: see text]