International prognostic scoring system for Waldenström s Macroglobulinemia Short title: Prognostic index for Waldenström Macroglobulinemia

Recently, many new drugs have been developed for the treatment of Waldenstrom’s macroglobulinemia (WM). In order to optimize the treatment according to the prognosis and to facilitate the comparison of trials we developed an international scoring system for WM (ISSWM) in a series of 587 patients with clearly defined criteria for diagnosis and for initiation of treatment. With a median follow-up of 64 months, the median survival after treatment initiation was 87 months. Five adverse covariates were identified: age >65 years, hemoglobin ≤11·5 g/dL, platelet count ≤100 x 10/L, s2-microglobulin >3 mg/L and serum monoclonal protein concentration >7.0 g/dL. Low risk patients (27% of patients) presented with ≤1 adverse characteristic and age ≤65 years, intermediate risk patients (38%) with 2 adverse characteristics or only age >65 years and high risk patients (35%) with >2 adverse characteristics. Five-year survival rates were 87%, 68% and 36% respectively (p 65 years, treatment with alkylating agent, and purine analogue. Thus, the combination of age, s2-microglobulin, monoclonal protein concentration and blood counts may provide a means to design risk-adapted studies. However, independent validation and new biological markers may enhance its significance. For personal use only. at Harvard Libraries on June 17, 2009. www.bloodjournal.org From