A New Prognostic Score for Advanced Systemic Mastocytosis Based on Clinical and Genetic Characteristics of 210 Consecutive Patients

According to the WHO classification, advanced systemic mastocytosis (advSM) comprises aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL). SM-AHN is the most common subtype of advSM, diagnosed in up to 80% of patients. The AHN is characterized in >90% of patients as a myeloid neoplasm, e.g. CMML. Acquired mutations in KIT (usually KIT D816V) are detectable in >90% of patients. The SM-AHN phenotype is usually based on clonal involvement of KIT D816V in various hematopoietic lineages, e.g. monocytes, eosinophils and other non-mast cell lineages. However, recent data have highlighted that the molecular pathogenesis of advSM is much more complex and involves one or more additional mutations (e.g. SRSF2, ASXL1, RUNX1, S/A/R gene panel) in 70-80% of the patients. The presence of at least one mutation of the S/A/R gene panel (S/A/Rpos) has a strong adverse impact on disease phenotype, prognosis, and response to treatment, e.g. midostaurin (Jawhar et al., Blood 2017). With data from 210 advSM patients enrolled in the 9German Registry on Disorders of Eosinophils and Mast Cells9, we evaluated a) clinical and genetic characteristics, b) treatment, c) survival and, d) developed a new prognostic score for advSM (Mannheim Prognostic Index, MPI). Subtypes of advSM included SM-AHN (n=166, 79%), ASM (n=26, 12%), and MCL ± AHN (n=18, 9%). Median age was 69 years (range 18-90, 67% male). The median MC infiltration in the bone marrow by histology and immunohistochemistry was 30% (range 5-100) and the median serum tryptase level was 168 μg/L (range 13-1854, normal value 1.0 in 34% of patients), eosinophils (0.3x109/L, >1.0 in 30% of patients), alkaline phosphatase (median 179 U/L, >150 in 58% of patients). Hypoalbuminemia ( 60 years (HR 2.4 [1.4-4.1], P=0.003), hemoglobin Disclosures Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Valent:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Reiter:Incyte: Consultancy, Honoraria.