title: Systemic mastocytosis in adults: 2011 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 prognostic relevance of the 2008 World Health Organization (WHO) classification of SM has recently been confirmed. 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.
  
  
  METHODS
  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, preliminary data suggest that Midostaurin may produce significant decreases in MC burden in some patients.
authors: Department of Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. pardanani.animesh@mayo.edu
authors: Animesh
authors: A
authors: Pardanani
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology; D017338:Cladribine / Q000008:administration & dosage / Q000627:therapeutic use; D000069439:Dasatinib; D018572:Disease-Free Survival; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins; D012306:Risk; D019311:Staurosporine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007370:Interferon Type I; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D013844:Thiazoles; D017338:Cladribine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D019311:Staurosporine; C059539:midostaurin; D000069439:Dasatinib; D006918:Hydroxyurea