title: Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management.
abstract: BACKGROUND
  Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.
  
  
  METHODS
  The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.
  
  
  METHODS
  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-MC lineage disease (SM-AHNMD) and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.
  
  
  RESULTS
  SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom-directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease-related organ dysfunction; interferon-α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator-release 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-sensitive KIT mutation or in KITD816-unmutated patients. Treatment of SM-AHNMD is governed primarily by the non-MC neoplasm; hydroxyurea has modest utility in this setting.
  Dasatinib's in vitro anti- KITD816V activity has not translated into significant therapeutic activity in most SM patients. In contrast, recently updated data confirms Midostaurin's significant anti-MC activity in patients with advanced SM.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001549:Benzamides / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018801:CD2 Antigens / Q000097:blood / Q000235:genetics; D017338:Cladribine / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000235:genetics; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010166:Palliative Care; D010879:Piperazines / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000097:blood / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use; D012307:Risk Factors; D053802:Tryptases / Q000097:blood / Q000235:genetics
chemical_list: D000305:Adrenal Cortex Hormones; D001549:Benzamides; D018801:CD2 Antigens; C508017:IL2RA protein, human; D016898:Interferon-alpha; D053645:Interleukin-2 Receptor alpha Subunit; D010879:Piperazines; D011743:Pyrimidines; D017338:Cladribine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases