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

• Verfasst von: Jawhar, Mohamad [VerfasserIn]
• Verfasst von: Schwaab, Juliana [VerfasserIn]
• Verfasst von: Hausmann, Daniel [VerfasserIn]
• Verfasst von: Clemens, Maja Josefine [VerfasserIn]
• Verfasst von: Naumann, Nicole [VerfasserIn]
• Verfasst von: Henzler, Thomas [VerfasserIn]
• Verfasst von: Schönberg, Stefan [VerfasserIn]
• Verfasst von: Fabarius, Alice [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Metzgeroth, Georgia [VerfasserIn]
• Verfasst von: Reiter, Andreas [VerfasserIn]
• Titel: Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis
• Verf.angabe: M. Jawhar, J. Schwaab, D. Hausmann, J. Clemens, N. Naumann, T. Henzler, H.-P. Horny, K. Sotlar, S. O. Schoenberg, N. C. P. Cross, A. Fabarius, W.-K. Hofmann, P. Valent, G. Metzgeroth and A. Reiter
• E-Jahr: 2016
• Jahr: 15 July 2016
• Umfang: 9 S.
• Fussnoten: Gesehen am 06.03.2019 ; advance online publication, 26 August 2016
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2016
• Band/Heft Quelle: 30(2016), 12, Seite 2342-2350
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/leu.2016.190
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1588388336

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.