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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Systemic mastocytosis is a clonal disease of mast cells, the immune cells that release histamine; almost every case is driven by a single mutation in the KIT gene. Precise KIT-blocking pills now shrink the mast cell burden, ease symptoms and, in the aggressive forms, prolong life. Most patients have the indolent form, where the goal is controlling symptoms and preventing anaphylaxis.
Systemic mastocytosis (SM) is a myeloid neoplasm defined by multifocal mast cell infiltrates in marrow or other organs, with KIT D816V present in about nine of ten patients. WHO 2022 divides it into indolent SM (ISM; the majority, with skin lesions, mediator symptoms and anaphylaxis risk but near-normal life expectancy), smouldering SM, and advanced SM (AdvSM), comprising aggressive SM, mast cell leukaemia and SM with an associated haematological neoplasm (SM-AHN), where the associated CMML, MDS or AML often decides outcome. Diagnosis uses serum tryptase (with correction for hereditary alpha-tryptasaemia), high-sensitivity KIT D816V PCR in peripheral blood, and marrow biopsy with CD25/CD30 mast cell immunophenotyping; additional mutations (SRSF2, ASXL1, RUNX1, the S/A/R panel) mark high-risk disease.
Treatment is stratified. In ISM, antihistamines, cromolyn, omalizumab, epinephrine autoinjectors and trigger avoidance manage mediator symptoms; osteoporosis is treated. The 2023 approval of avapritinib for ISM (PIONEER: 25 mg daily improved total symptom scores and reduced tryptase, KIT D816V allele burden and skin lesions) made it the first disease-modifying therapy for the indolent form. In AdvSM, midostaurin (2017; multikinase KIT inhibitor, responses in about 60 percent in the pivotal trial) was the first approved drug, and avapritinib (2021; PATHFINDER and EXPLORER, selective KIT D816V inhibition with high response rates including complete remissions) is now the preferred first-line agent for patients with platelets above 50 x 10^9/L. Cladribine remains an option, interferon is historic, and allogeneic transplant is used for mast cell leukaemia or SM-AHN with high-risk associated neoplasms. Next-generation KIT D816V inhibitors, bezuclastinib (Summit and Apex trials) and elenestinib (Harbor), aim for equal efficacy with less intracranial bleeding and cognitive toxicity.
| Setting | Approach | Guideline |
|---|---|---|
| Indolent SM, symptomatic | H1 and H2 antihistamines, cromolyn, leukotriene antagonists, omalizumab for anaphylaxis, epinephrine autoinjector, bone protection; avapritinib 25 mg daily for moderate to severe symptoms uncontrolled by these (PIONEER). | NCCN Category 2A |
| Advanced SM, first line | Avapritinib 200 mg daily (platelets above 50 x 10^9/L) as preferred agent; midostaurin as alternative or where platelets are low. | NCCN Category 2A (preferred: avapritinib) |
| Advanced SM, subsequent lines | Switch between avapritinib and midostaurin; cladribine; clinical trials (bezuclastinib, elenestinib); allogeneic transplant for mast cell leukaemia or high-risk SM-AHN. | not mapped |
| SM-AHN | Treat the dominant component: KIT inhibitor for mast cell burden plus the standard therapy for the associated CMML, MDS or AML (hypomethylating agents, intensive chemotherapy, transplant). | not mapped |