Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)
Advanced systemic mastocytosis is the dangerous form of this rare blood cancer, in which KIT-mutant mast cells damage the marrow, liver, gut or bones, grow alongside a second blood cancer such as chronic myelomonocytic leukaemia, or flood the blood as mast cell leukaemia. The KIT-blocking tablets midostaurin and avapritinib have replaced older chemotherapy, and fit patients may have a transplant.
Overview
Advanced systemic mastocytosis comprises three WHO entities united by KIT D816V-driven mast cell proliferation with organ damage or an accompanying neoplasm. Aggressive systemic mastocytosis is defined by C findings: cytopenias from marrow infiltration, liver dysfunction with ascites, hypoalbuminaemia and weight loss from gut involvement, or large lytic bone lesions. Systemic mastocytosis with an associated haematological neoplasm (SM-AHN), the commonest advanced form, pairs mastocytosis with a myeloid neoplasm, usually chronic myelomonocytic leukaemia, a myelodysplastic or myeloproliferative neoplasm or acute myeloid leukaemia, which arises from the same KIT-mutant or an earlier clone and often carries SRSF2, ASXL1 or RUNX1 mutations that predict poor survival on the MARS and IPSM scores. Mast cell leukaemia, with 20 percent or more mast cells in the marrow aspirate, is the rarest and most lethal form. Serum tryptase is usually very high and KIT D816V allele burden in blood reflects the whole disease.
Before 2017 treatment was cladribine, interferon alfa or hydroxycarbamide, with responses in a minority. Midostaurin, a multikinase inhibitor active against KIT D816V, produced responses in 60 percent of 116 patients with advanced disease in a phase 2 trial (New England Journal of Medicine 2016) and was approved in 2017; avapritinib, a selective KIT D816V inhibitor, produced responses in three quarters of patients in the EXPLORER and PATHFINDER trials with deep falls in tryptase and allele burden and was approved in June 2021 for advanced disease, restricted to patients with platelets of 50 x 10^9/L or more because of intracranial haemorrhage at higher doses in thrombocytopenic patients. Avapritinib is now the preferred first-line agent in the NCCN guideline, midostaurin the alternative, and bezuclastinib is in the Apex trial as a further selective inhibitor. The associated neoplasm is treated on its own merits, for example with azacitidine for chronic myelomonocytic leukaemia or intensive chemotherapy for acute myeloid leukaemia, and allogeneic transplantation is the only curative option, considered for mast cell leukaemia, aggressive disease responding to a KIT inhibitor and SM-AHN with a high-risk neoplasm. Supportive care for mediator symptoms, bone disease and anaphylaxis continues throughout.
State of the art
- KIT-selective inhibition with avapritinib produces deep molecular responses in most patients.
- Midostaurin and avapritinib gave the disease its first approved drugs within four years.
- Prognostic scores incorporating myeloid mutations guide the decision to transplant.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Check before combiningFood and drink: Midostaurin
Take with food; antiemetic prophylaxis.
- Check before combiningHeart rhythm (QT): Midostaurin
Possible QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
See all on the product pages:AvapritinibAzacitidineCladribineMidostaurin·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)Aggressive systemic mastocytosis (C findings: cytopenias, liver, gut or bone damage) · Systemic mastocytosis with an associated haematological neoplasm (SM-AHN; usually CMML, MDS or MPN) · Systemic mastocytosis with acute myeloid leukaemia (SM-AML) · Mast cell leukaemia (20 percent or more marrow mast cells; acute or chronic) · Advanced systemic mastocytosis with SRSF2, ASXL1 or RUNX1 mutations (high-risk) · Advanced systemic mastocytosis with thrombocytopenia (avapritinib restricted)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- A minority of systemic mastocytosis, mostly in older adults; survival was measured in months for mast cell leukaemia and a few years for aggressive disease before KIT inhibitors, and the associated haematological neoplasm often determines the outcome.
- Liquid biopsy (ctDNA)Standard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bone marrow biopsy and aspirate, KIT D816V allele burden, myeloid mutation panel, tryptase, imaging for organomegaly and bone lesions, MARS or IPSM score.
Avapritinib 200 mg daily when platelets are 50 x 10^9/L or more (EXPLORER, PATHFINDER, approved 2021); midostaurin as the alternative (approved 2017).
Treat the neoplasm on its own merits (azacitidine for CMML or MDS, intensive chemotherapy for AML) alongside or after KIT inhibition.
Switch between avapritinib and midostaurin; cladribine; interferon alfa; bezuclastinib in the Apex trial.
Allogeneic haematopoietic cell transplantation after response to a KIT inhibitor.
Subtypes & biomarkers
top- Aggressive systemic mastocytosis (C findings: cytopenias, liver, gut or bone damage)
- Systemic mastocytosis with an associated haematological neoplasm (SM-AHN; usually CMML, MDS or MPN)
- Systemic mastocytosis with acute myeloid leukaemia (SM-AML)
- Mast cell leukaemia (20 percent or more marrow mast cells; acute or chronic)
- Advanced systemic mastocytosis with SRSF2, ASXL1 or RUNX1 mutations (high-risk)
- Advanced systemic mastocytosis with thrombocytopenia (avapritinib restricted)
- C findings (cytopenias, liver dysfunction, hypoalbuminaemia, malabsorption, lytic bone lesions)
- Serum tryptase and KIT D816V allele burden (response and molecular remission)
- Mast cell percentage in marrow aspirate (20 percent defines mast cell leukaemia)
- SRSF2, ASXL1 and RUNX1 mutations; MARS and IPSM prognostic scores
- Platelet count (avapritinib eligibility above 50 x 10^9/L)
- Molecular and morphological characterisation of the associated neoplasm
How often this target appears
- 1991Mast cell leukaemia and aggressive mastocytosis defined as distinct categories
- 2007Cladribine reported as active in advanced mastocytosis
- 2016Midostaurin phase 2: 60 percent response rate in advanced systemic mastocytosis
- 2017Midostaurin approved for advanced systemic mastocytosis
- 2021Avapritinib approved for advanced systemic mastocytosis after EXPLORER and PATHFINDER
- 2022WHO and ICC classifications update advanced disease criteria
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 9 changes by month →- 2026-09-18This recordAdvanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)Facts on this page last checked
When this page itself was last checked or edited.
- 2022MilestoneKITWHO and ICC classifications update advanced disease criteria
A milestone in how this cancer is treated.
- 2021ApprovalAvapritinibAvapritinib approved in US
Advanced systemic mastocytosis
- 2021MilestoneAvapritinibAvapritinib approved for advanced systemic mastocytosis after EXPLORER and PATHFINDER
A milestone in how this cancer is treated.
- 2017ApprovalMidostaurinMidostaurin approved in US
Newly diagnosed FLT3-mutated AML with 7+3 and consolidation; advanced systemic mastocytosis
- 2017MilestoneMidostaurinMidostaurin approved for advanced systemic mastocytosis
A milestone in how this cancer is treated.
What is in development for Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 1
Trials under way · 1
- (Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis · phase 2 · Cogent Biosciences, Inc.
Open problems and what is being done
The associated myeloid neoplasm, not the mast cells, now causes most deaths in SM-AHN.
Whether KIT inhibitors improve survival has not been shown in a randomised trial.
Thrombocytopenic patients cannot receive avapritinib safely.
Transplant outcomes rest on small retrospective series.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Boston · hospital | United States | 0 | 3,582 | 54,857 | #16 | ||
Barcelona · hospital | Spain | none recorded | 0 | 1,265 | 15,631 | - | |
Lyon · cancer center | France | none recorded | 0 | 1,071 | 14,301 | - | |
Oslo · cancer center | Norway | none recorded | 0 | 936 | 11,600 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Taipei · hospital | Taiwan | none recorded | 0 | 746 | 8,966 | - | |
Marseille · cancer center | France | none recorded | 0 | 738 | 7,479 | - | |
Guangzhou · hospital | China | none recorded | 0 | 704 | 7,832 | - | |
Nagoya · cancer center | Japan | none recorded | 0 | 657 | 8,832 | - | |
Shanghai · hospital | China | none recorded | 0 | 539 | 6,491 | - | |
Osaka · cancer center | Japan | none recorded | 0 | 505 | 4,266 | - | |
Ghent · hospital | Belgium | none recorded | 0 | 495 | 5,334 | - | |
Aurora, CO · cancer center | United States | 0 | 483 | 13,480 | - | ||
| Switzerland | none recorded | 0 | 470 | 4,598 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Advanced systemic mastocytosis but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Advanced systemic mastocytosis
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example C findings, Serum tryptase and KIT D816V allele burden, Mast cell percentage in marrow aspirate, SRSF2, ASXL1 and RUNX1 mutations; MARS and IPSM prognostic scores, Platelet count), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Aggressive systemic mastocytosis, Systemic mastocytosis with an associated haematological neoplasm, Systemic mastocytosis with acute myeloid leukaemia.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis and risk assessment
- For my situation (diagnosis and risk assessment), which of the standard options do you recommend and why?Why: Guideline options include: Bone marrow biopsy and aspirate, KIT D816V allele burden, myeloid mutation panel, tryptase, imaging for organomegaly and bone lesions, MARS or IPSM score.
First line
- For my situation (first line), which of the standard options do you recommend and why?Why: Guideline options include: Avapritinib 200 mg daily when platelets are 50 x 10^9/L or more (EXPLORER, PATHFINDER, approved 2021); midostaurin as the alternative (approved 2017).
- Am I a candidate for Avapritinib, Midostaurin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Associated haematological neoplasm
- For my situation (associated haematological neoplasm), which of the standard options do you recommend and why?Why: Guideline options include: Treat the neoplasm on its own merits (azacitidine for CMML or MDS, intensive chemotherapy for AML) alongside or after KIT inhibition.
- Am I a candidate for Azacitidine, Midostaurin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed or intolerant
- For my situation (relapsed or intolerant), which of the standard options do you recommend and why?Why: Guideline options include: Switch between avapritinib and midostaurin; cladribine; interferon alfa; bezuclastinib in the Apex trial.
- Am I a candidate for Cladribine, Interferon alfa-2a/2b, Bezuclastinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of (Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Fit patients, especially mast cell leukaemia or high-risk SM-AHN
- For my situation (fit patients, especially mast cell leukaemia or high-risk sm-ahn), which of the standard options do you recommend and why?Why: Guideline options include: Allogeneic haematopoietic cell transplantation after response to a KIT inhibitor.
Any stage
- Are there clinical trials I could join, for example of Avapritinib, Bezuclastinib, (Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis, Allogeneic stem cell transplantation?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “The associated myeloid neoplasm, not the mast cells, now causes most deaths in SM-AHN”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether KIT inhibitors improve survival has not been shown in a randomised trial”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Advanced systemic mastocytosis, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
8targets
3drugs
6companies
7terms
3trials
1key papers
4The names and definitions on a marrow report (for example MDS with biallelic TP53 inactivation, or AML myelodysplasia-related) come from this document or from the parallel International Consensus Classification.
Avapritinib is the most active drug in advanced systemic mastocytosis; platelet counts must be checked before and during treatment.
Avapritinib is the preferred first targeted therapy for advanced systemic mastocytosis in patients with adequate platelet counts.
Midostaurin was the first effective targeted therapy for advanced systemic mastocytosis and remains an option, particularly where avapritinib is unsuitable or unavailable.
Latest papers
topQuery for this cancer: (TITLE:"Advanced systemic mastocytosis" OR ABSTRACT:"Advanced systemic mastocytosis" OR TITLE:"aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia" OR ABSTRACT:"aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia" OR TITLE:"AdvSM" OR ABSTRACT:"AdvSM" OR TITLE:"Aggressive systemic mastocytosis" OR ABSTRACT:"Aggressive systemic mastocytosis" OR TITLE:"ASM" OR ABSTRACT:"ASM" OR TITLE:"SM-AHN" OR ABSTRACT:"SM-AHN") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), not a curated reading list.
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