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Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and\/or CD2, and presence of <jats:italic>KIT<\/jats:italic>D816V.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:bold>Risk stratification:<\/jats:bold> The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non\u2010MC lineage disease (SM\u2010AHNMD) and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:bold>Management<\/jats:bold>: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom\u2010directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease\u2010related organ dysfunction; interferon\u2010\u03b1 (\u00b1corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal and mediator\u2010release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib\u2010sensitive KIT mutation or in <jats:italic>KIT<\/jats:italic>D816\u2010unmutated patients. Treatment of SM\u2010AHNMD is governed primarily by the non\u2010MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:bold>Investigational drugs<\/jats:bold>: Recent data confirms midostaurin's significant anti\u2010MC activity in patients with advanced SM. Am. J. 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