A new 2026 update in the American Journal of Hematology builds on the 2022 International Consensus Classification (ICC) and World Health Organization (WHO) classification systems and outlines current approaches to diagnosis, risk stratification and management for adults with systemic mastocytosis (SM).
The review presents SM subtype as an important first step in risk stratification, which supports treatment planning. Broadly, the disease is grouped into nonadvanced forms, such as indolent or smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form. (ISM/SSM) and advanced forms, including aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases. (ASM), SM with an associated myeloid neoplasm (SM-AMN) and mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis..
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The update also highlights genetic mutations that can help estimate how the disease may behave over time. Poor-risk mutations, including ASXL1, RUNX1, SRSF2 and NRAS, may refine risk estimates after the subtype is identified.
Diagnosing SM usually involves putting together several objective findings, each functioning as a criterion toward the diagnosis. These typically include the pattern of abnormal mast cells in the bone marrow or other organs, serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. levels, mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. markers such as CD25, CD2 or CD30, and activating KIT mutations.
Read more about SM testing and diagnosis
Besides SM subtype, treatment planning depends on symptoms, organ involvement and risk profile. For example, a patient with nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM. and mainly allergy-like symptoms may need care focused on preventing anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis. and controlling symptoms such as flushing, itching or gastrointestinal problems.
The update emphasizes how targeted drugs have changed SM care. As Dr. Animesh Pardanani, author of the review, notes, “tyrosine kinase inhibitors (TKITyrosine kinase inhibitor Targeted therapies designed to block the KIT D816V mutation that drives most cases of SM. Includes avapritinib, midostaurin and imatinib.) (midostaurin, avapritinib) have changed the treatment landscape in SM.” These drugs can act on KIT, a mutation-driven pathway involved in many cases of SM, making treatment more targeted.
This shift may be especially important in advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm., where abnormal mast cells can damage organs and targeted treatment may have a greater impact on quality of life and disease outcomes — though researchers note that longer follow-up is still needed to fully understand how these treatments affect disease progression over time.
For patients, the update reinforces that an SM diagnosis is only the starting point. The subtype, mutation profile, symptoms and signs of organ involvement can all affect monitoring and treatment planning. Patients may want to ask which SM subtype they have, whether mutation testing was done and how their risk profile affects follow-up or treatment options.
