Systemic mastocytosis in adults

2013 update on diagnosis, risk stratification, and management

Research output: Contribution to journalArticle

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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 (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. 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. Investigational drugs: 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.

Original languageEnglish (US)
Pages (from-to)612-624
Number of pages13
JournalAmerican Journal of Hematology
Volume88
Issue number7
DOIs
StatePublished - Jul 2013

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Systemic Mastocytosis
Risk Management
Mast Cells
4'-N-benzoylstaurosporine
Therapeutics
Mast-Cell Leukemia
Cladribine
Investigational Drugs
Tryptases
Hydroxyurea
Cell Lineage
Life Expectancy
Interferons
Adrenal Cortex Hormones

ASJC Scopus subject areas

  • Hematology

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Systemic mastocytosis in adults : 2013 update on diagnosis, risk stratification, and management. / Pardanani, Animesh D.

In: American Journal of Hematology, Vol. 88, No. 7, 07.2013, p. 612-624.

Research output: Contribution to journalArticle

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