Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

Jawhar, M.; Schwaab, J.; Hausmann, D.; Clemens, J.; Naumann, N.; Henzler, T.; Horny, H.-P.; Sotlar, K.; Schoenberg, S. O.; Cross, N. C. P.; Fabarius, A.; Hofmann, W.-K.; Valent, P.; Metzgeroth, G. und Reiter, A. (2016): Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis. In: Leukemia, Bd. 30, Nr. 12: S. 2342-2350

Abstract

We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n = 41) and advanced systemic mastocytosis (SM) (advSM, n = 67). Organomegaly was measured by magnetic resonance imaging-based volumetry of the liver and spleen. In multivariate analysis of all patients, an increased spleen volume >= 450 ml (hazard ratio (HR), 5.2;95% confidence interval (CI), (2.1-13.0);P = 0.003) and an elevated alkaline phosphatase (AP;HR 5.0 (1.1-22.2);P = 0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low risk, n = 37), 1 (intermediate risk, n = 32) or 2 (high risk, n = 39) parameters. For advSM patients with fully available clinical and molecular data (n = 60), univariate analysis identified splenomegaly. 1200 ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR 3.2 (1.1-9.6);P = 0.01) and elevated AP (HR 2.6 (1.0-7.1);P = 0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76 and 38%, respectively (P = 0.0003), for patients with 0-1 (intermediate risk, n = 28) or 2 (high risk, n = 32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the World Health Organization classification and provide the most relevant prognostic information in SM patients.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0887-6924
• Sprache: Englisch