Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Am J Hematol. 2015 Mar;90(3):250-62. doi: 10.1002/ajh.23931.

Abstract

Disease overview: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.

Diagnosis: 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.

Risk stratification: The 2008 World Health Organization classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent SM (ISM), 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.

Management: 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; there is a role for allogeneic stem cell transplantation in select cases. Investigational Drugs: Recent data confirms midostaurin's significant anti-MC activity in patients with advanced SM.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Benzamides / therapeutic use
  • Bone Marrow / drug effects*
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cell Proliferation
  • Cladribine / therapeutic use
  • Disease Management
  • Humans
  • Imatinib Mesylate
  • Interferon-alpha / therapeutic use
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Mastocytosis, Systemic / diagnosis*
  • Mastocytosis, Systemic / drug therapy*
  • Mastocytosis, Systemic / genetics
  • Mastocytosis, Systemic / pathology
  • Mutation
  • Piperazines / therapeutic use
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pyrimidines / therapeutic use
  • Risk Factors
  • Severity of Illness Index
  • Tryptases / blood

Substances

  • Adrenal Cortex Hormones
  • Antineoplastic Agents
  • Benzamides
  • Interferon-alpha
  • Piperazines
  • Pyrimidines
  • Cladribine
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Tryptases