Mars: Mutation-adjusted risk score for advanced systemic mastocytosis

Mohamad Jawhar*, Juliana Schwaab, Iván Álvarez-Twose, Khalid Shoumariyeh, Nicole Naumann, Johannes Lübke, Cecelia Perkins, Javier I. Muñoz-González, Manja Meggendorfer, Vanessa Kennedy, Georgia Metzgeroth, Alice Fabarius, Dietmar Pfeifer, Karl Sotlar, Hans Peter Horny, Nikolas Von Bubnoff, Torsten Haferlach, Nicholas C.P. Cross, Wolf Karsten Hofmann, Wolfgang R. SperrAndrés C. García-Montero, Peter Valent, Jason Gotlib, Alberto Orfao, Andreas Reiter

*Corresponding author for this work
26 Citations (Scopus)


PURPOSE: To develop a risk score for patients with advanced systemic mastocytosis (AdvSM) that integrates clinical and mutation characteristics. PATIENTS AND METHODS: The study included 383 patients with AdvSM from the German Registry on Disorders of Eosinophils and Mast Cells (training set; n = 231) and several centers for mastocytosis in the United States and Europe, all within the European Competence Network on Mastocytosis (validation set; n = 152). A Cox multivariable model was used to select variables that were predictive of overall survival (OS). RESULTS: In multivariable analysis, the following risk factors were identified as being associated with OS: age greater than 60 years, anemia (hemoglobin, 10 g/dL), thrombocytopenia (platelets, 100 3 109/L), presence of one high molecular risk gene mutation (ie, in SRSF2, ASXL1, and/or RUNX1), and presence of two or more high molecular risk gene mutations. By assigning hazard ratio-weighted points to these variables, the following three risk categories were defined: low risk (median OS, not reached), intermediate risk (median OS, 3.9 years; 95% CI, 2.1 to 5.7 years), and high risk (median OS, 1.9 years; 95% CI, 1.3 to 2.6 years; P, .001). The mutation-adjusted risk score (MARS) was independent of the WHO classification and was confirmed in the independent validation set. During a median follow-up time of 2.2 years (range, 0 to 23 years), 63 (16%) of 383 patients experienced a leukemic transformation to secondary mast cell leukemia (32%) or secondary acute myeloid leukemia (68%). The MARS was also predictive for leukemia-free survival (P, .001). CONCLUSION: The MARS is a validated, five-parameter, WHO-independent prognostic score that defines three risk groups among patients with AdvSM and may improve up-front treatment stratification for these rare hematologic neoplasms.

Original languageEnglish
JournalJournal of Clinical Oncology
Issue number31
Pages (from-to)2846-2856
Number of pages11
Publication statusPublished - 2019


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