MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis

Abstract

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 × 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.

Trichinella spiralis-induced mastocytosis and erythropoiesis are simultaneously supported by a bipotent mast cell/erythrocyte precursor cell

“…Interestingly, recent human studies have highlighted an association between allergic disease and anemia [30][31][32]. Further, it is well established that patients suffering from mastocytosis also present with severe anemia [33,34]. Although several plausible explanations have been proposed to explain these associations, including the possibility that mast cell-derived effector molecules kill erythrocytes, it is possible that they might be the result of a defective development branch point that forces the overabundance of mast cells to the detriment of erythrocytes.…”

Discordant Response of Systemic Mastocytosis Associated With Myelodysplastic Syndrome After Midostaurin and Allogeneic Hematopoietic Stem‐cell Transplantation

“…Combination therapies with midostaurin and allogenic HSCT in eligible candidates should be considered for these patients. 9 …”

Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis

“…Recent studies have shown that in >60% of all patients with advanced SM (ASM, SM-AHN or MCL), neoplastic cells harbor somatic variants in relevant genes other than KIT [ 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. These additional mutations affect genes encoding transcription factors (e.g., RUNX1 ), signaling molecules ( JAK , KRAS , NRAS , CBL ), epigenetic regulators ( TET2 , ASXL1 , DNMT3A , EZH2 ) or splicing factors ( SRSF2 , SF3B1 , U2AF1 ).…”