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Chronic myeloproliferative neoplasms

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

Leukemia volume 30, pages 2342–2350 (2016)Cite this article

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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.

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Acknowledgements

This work was supported by the ‘Deutsche José Carreras Leukämie-Stiftung e.V.’ (grant no. DJCLS H 11/03 and R 13/05) and the Austrian Science Fund (FWF) grant SFB F4704-B20.

Author contributions

MJ, JS, DH, JC, NN, TH, SOS, NCPC, AF and AR performed the laboratory/volumetric work for the study. MJ, JS, JC, GM, W-KH, PV, GM and AR provided patient material and information. H-PH and KS reviewed the bone marrow biopsies. MJ, JS, DH, JC, TH, NCPC, AF, W-KH, PV and AR wrote the paper.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany

    M Jawhar, J Schwaab, J Clemens, N Naumann, A Fabarius, W-K Hofmann, G Metzgeroth & A Reiter

  2. Institute of Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Mannheim, Germany

    D Hausmann, T Henzler & S O Schoenberg

  3. Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany

    H-P Horny & K Sotlar

  4. Wessex Regional Genetics Laboratory, Salisbury, UK

    N C P Cross

  5. Faculty of Medicine, University of Southampton, Southampton, UK

    N C P Cross

  6. Department of Internal Medicine I, Division of Hematology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria

    P Valent

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Jawhar, M., Schwaab, J., Hausmann, D. et al. Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis. Leukemia 30, 2342–2350 (2016). https://doi.org/10.1038/leu.2016.190

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