What question did this study set out to answer?

This work aims to update on the diagnosis, risk stratification, and management of systemic mastocytosis in adults.

June 20, 2026

Systemic Mastocytosis in Adults: 2026 Update on Diagnosis, Risk Stratification and Management

Key Points

This work aims to update on the diagnosis, risk stratification, and management of systemic mastocytosis in adults.
Detailed overview of diagnostic criteria for SM, including major and minor criteria.
Information on risk stratification using international classification systems and identification of poor-risk mutations.
Discussion on treatment options including tyrosine kinase inhibitors and other therapeutic approaches.
Identification of poor-risk mutations improves prognosis accuracy in systemic mastocytosis patients.
Tyrosine kinase inhibitors have significantly advanced treatment options, but efficacy in multimutated cases needs further assessment.
Management strategies vary significantly between indolent and advanced systemic mastocytosis.

Abstract

OVERVIEW: Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extra-cutaneous organs. DIAGNOSIS: The major criterion is the presence of multifocal MC clusters in the bone marrow and/or extracutaneous organs. Minor diagnostic criteria include elevated serum tryptase level, MC CD25/CD2/CD30 expression, and the presence of activating KIT mutations. RISK STRATIFICATION: Establishing SM subtype as per the International Consensus Classification/World Health Organization classification systems is an important first step. Patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, including aggressive SM (ASM), SM with associated myeloid neoplasm (SM-AMN), or mast cell leukemia. Identification of poor-risk mutations (i.e., ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Several risk models are available to help assign prognosis in SM patients. MANAGEMENT: Treatment goals for ISM patients are primarily directed towards anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to reverse disease-related organ dysfunction. Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM. While deep biochemical, histological, and molecular responses have been documented with avapritinib treatment, its efficacy as monotherapy against a multimutated AMN disease component in SM-AMN patients remains unclear. Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era. Treatment of SM-AMN primarily targets the AMN component, particularly if an aggressive disease such as acute leukemia is present. Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation.

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