SM Variant Type Probability Calculator

DISCLAIMER: This tool is intended to aid healthcare providers in the differentiation between indolent systemic mastocytosis (SM) and advanced SM. This tool is for informational purposes only and should not be used without confirming the patient's diagnosis based on the World Health Organization (WHO) 2024 diagnostic criteria (5th ed.) ^{1, 2} or as a substitute for clinical judgement.

Instructions:

• Required Fields: Please enter values for Tryptase, Alkaline Phosphatase (U/L), Absolute Monocyte Count (x10^9 cells/L or cells/µL), Age (years), Absolute Lymphocyte Count (x10^9 cells/L or cells/µL), Albumin (g/L or g/dL), and Total Bilirubin (µmol/L or mg/dL).
• Optional Fields: If you have Platelets (10^9/L) and Hemoglobin (g/L or g/dL), enter them to use Formula 1. If not, Formula 2 will be used.

 

Enter values here:

Tryptase: ng/mL µg/L

Alkaline Phosphatase (U/L):

Absolute Monocyte Count: x10^9 cells/L cells/µL

Age (years):

Absolute Lymphocyte Count: x10^9 cells/L cells/µL

Albumin: g/L g/dL

Total Bilirubin: µmol/L mg/dL

Platelets (10^9/L):

Hemoglobin: g/L g/dL

 

 

 

 

 

SM Diagnostic Criteria
Major Criteria
Multifocal dense infiltrates of mast cells (≥15 mast cells in aggregates) in bone marrow biopsies and/or in sections of other extracutaneous organ(s).
Minor Criteria
≥25% of mast cells are atypical cells on bone marrow smears or are spindle-shaped in mast cell infiltrates detected in bone marrow or other extracutaneous organs. KIT-activating KIT point mutation(s) at codon 816 or in other critical regions of KIT in bone marrow or another extracutaneous organ. Mast cells in bone marrow, blood, or another extracutaneous organ express one or more of: CD2 and/or CD25 and/or CD30. Baseline serum tryptase concentration >20 ng/mL (in the case of an unrelated myeloid neoplasm, an elevated tryptase does not count as an SM criterion. In the case of a known HαT, the tryptase level should be adjusted).
B Findings
Mast cells in BM ≥30% in histology (IHC) and/or serum tryptase ≥200 ng/mL and/or KIT D816V VAF ≥10%. Signs of myeloproliferation and/or myelodysplasia. Hypercellular marrow with loss of fat cells and prominent myelopoiesis ± left shift, eosinophilia, leukocytosis. Palpable hepatomegaly without ascites or end organ damage, palpable splenomegaly without hypersplenism, or lymphadenopathy (>2 cm).
C Findings
Cytopenias: (one or more found) ANC < 1 × 10⁹/L Hb < 10 g/dL PLT < 100 × 10⁹/L Ascites and elevated liver enzymes ± hepatomegaly or cirrhotic liver ± portal hypertension. Palpable splenomegaly with hypersplenism ± weight loss ± hypoalbuminemia. Malabsorption with hypoalbuminemia ± weight loss. Large-sized osteolytic lesions (≥2 cm) with pathologic fracture ± bone pain.
Subtypes of SM
Indolent SM: Meets criteria for SM, no C findings. Smoldering SM: Meets criteria for SM, > 2 B findings, no C findings. Advanced SM: Aggressive SM: Meets Criteria for SM, > 1 C finding, no AHN or MCL. SM-AHN: Meets Criteria for SM, with an additional associated hematologic neoplasm per WHO 2022. MCL: Meets SM criteria, > 20% mast cells in the bone marrow.

References:

1. Khoury JD, et al. The 5th Edition of the World Health Organization of Haematolymphoid Tumours – Myeloid and Histiocytic / Dendritic Neoplasms. Leukemia. 2022; 36:1703–1719.
2. Valent P et al. Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal. Hemasphere. 2021;5:e646.
3. Lampson B, Zakharyan A, Volpe V, Shimony S, Shi H, and DeAngelo D. Analysis of Avapritinib Clinical Trial Data Generates a Highly Accurate Predictive Model for Advanced Systemic Mastocytosis Versus Indolent Systemic Mastocytosis Based on Peripheral Blood Testing. ASH 2024.