Systemic Mastocytosis (SM)

CD2+, CD25+ Mast Cells

KIT D816V mutation (or other exon 17)

 

WHO Criteria (1 major + 1 minor, or 3 minor)

 

Major

Multifocal, dense infiltrates (>15 mast cells in aggregates) in marrow or extracutaneous organs.

 

Minor

>25% mast cells with spindled / atypical morphology

KIT point mutation at codon 816 (KIT D816V)

CD2 of CD25 expression in mast cells

Serum tryptase >20 ng/ml, unless there is an associated clonal myeloid disorder

 

2016 WHO Classification of Systemic Mastocytosis

 

ISM - Indolent SM

  • ISM-AHN

SSM - Smouldering SM

SM with AHN - with associated clonal, haematologic non-mast cell lineage disease

ASM - Aggressive SM

  • ASM-AHN

  • ASM-slow

  • ASM-rapid

  • ASM in transformation to MCL (ASM-t)

MCL - Mast cell leukaemia

  • Chronic MCL (cMCL)

  • Acute MCL (aMCL)

 

Clinical Presentation

 

Features of mast cell degranulation (‘mediator’ symptoms)

  • Anaphylaxis, flushing, itch, N&V, diarrhoea, lightheadedness, severe hypotension, bone paine, neuropsychiatric distrubance

  • Often no identifiable triggers

 

Staging Work-Up

 

Serum total tryptase

BM Biopsy

Relevant organ biopsy

KITD816V mutation (or other exon 17)

CD2 / CD25 Mast cell expression

If eosinophilia, screen for FIP1L1-PDGFRA

 

Indolent / Smouldering / Advanced

 

Indolent

  • No B or C findings

 

Smouldering: 2 or more B Findings

  • BM >30% mast cells + Tryptase >200 ng/ml

  • Signs of dysplasia or myeloproliferation without frank AHN, & normal FBC

  • Hepatomegaly without liver dysfunction and/or splenomegaly without hypersplenism

 

Advanced (ASM, MCL, SM-AHN with organ damage): C Findings, ie organ damage

  • One or more cytopenias

  • Hepatomegaly with liver dysfunction

  • Osteolytic lesions or fractures

  • Splenomegaly with hypersplenism

  • Malabsorption with weight loss due to GI infiltration

 

Management

 

Avoidance of triggers

 

Treatment of mediator symptoms

  • EpiPen

  • H1 anti-histamines (Cetirizine, Fexofenadine, Hydroxyzine)

  • H2 antagonists (Ranitidine, Cimetidine)

  • Leukotriene antagonists (Montelukast)

  • Bisphosphonates for osteoporosis / bone pain / fractures

  • Mast cell stabilisers (ketotifen, cromolyn)

  • PUVA light therapy

  • NSAID - Aspirin

 

Cytoreductive Therapy

  • Steroids

  • PEG Interferon alpha

  • Multi-agent chemotherapy

  • Cladribine (approx. 50% response rate)

  • Transplant

 

Targeted Therapies / Trials (Presence of KIT D816V confers resistance against many TKI’s)

  • Midostaurin (KIT inhibitor) (60% ORR)

  • Dasatinib / Nilotinib

  • Mastinib

  • Imatinib

  • Everolimus

  • Mabs – Daclizumab, Omalizumab

  • Other Mabs to consider based on pt’s immunophenotype – CD30, CD33, CD52, CD123

 

Mast Cell Activation Syndrome (MCAS)

 

Meeting only 1 or 2 of the minor diagnostic criteria

Lack the characteristic BM mast cell aggregates

Episodic symptoms of mast cell degranulation