1. Lauren A. Ebbecke

2. Introduction Systemic Mastocytosis – abnormal growth and aggregation of mast cells in more than one organ Liver, spleen, skin, gastrointestinal, bone marrow, lymph nodes 80% of patients have the D816V c-kit mutation

3. Introduction Listed below are some of the symptoms that people with SM can experience : Rashes or Itchingloss of consciousness hypotensionanaphylactic reactions osteoporosis gastrointestinal upsets Nausea or vomitingDiarrhea AnemiaFlushing WheezingDizziness Reduced Blood PlateletsLeukopenia

4. Methods Sixteen papers were reviewed from 1999-2010 based on the following criteria: Clinical studies of patients with SM Advances in SM research Classification of SM Diagnosis of SM

5. RESEARCH WHO Classification Cutaneous Mastocytosis (CM) Indolent Systemic Mastocytosis (ISM) Systemic Mastocytosis with an associated clonal hematological non mast cell lineage disease (SM-AHNMD) Aggressive Systemic Mastocytosis (ASM) Mast Cell Leukemia (MCL) Mast Cell Sarcoma Extracutaneous Mastocytoma

6. Major Criteria Multifocal dense mast cell (MC) infiltrates ≥15% in the bone marrow or in an other extracutaneous organ Minor Criteria >25% spindle-shaped cells in Mast Cell infiltrates; or >25% of all MC are atypical MC (type I and/or type II) in bone marrow smears Expression of CD2 and/or CD25 on bone marrow MC Serum tryptase level >20 ng/ml (does not count in cases with an AHNMD) c-kitpoint mutation at codon 816 (mostly D816V) in bone marrow or in another extracutaneous organ RESEARCH WHO Classification for SM

7. RESEARCH WHO Classification for SM continued…. Diagnosis of SM 1 major criteria and 1 minor criteria have been met 3 minor criteria have been met

8. RESEARCH Systemic Mastocytosis has two major classes Slow growing in the bone known as Indolent Systemic Mastocytosis (ISM) Aggressive Systemic Mastocytosis (ASM) can lead Mast Cell Leukemia Photos courtesy of the Pathological Society of Great Britain

9. RESEARCH Hematopoietic Stem cell Systemic Mastocytosis SM Indolent Systemic Mastocytosis ISM Bone Marrow Mastocytosis BMM Smouldering Systemic Mastocytosis SSM Aggressive Systemic Mastocytosis ASM Mast Cell Leukemia MCL SM-AHNMD ASM, MCL, and SM-AHNMD Have a very poor prognosis (death).

10. RESEARCH Treatment Options Mediator type symptoms Drugs targeting Mediator Production, Release and Effects Cytoreductive Therapy Drugs Neoplastic stem cells – Progenitor cells, Mast Cells – Specific Molecular Targets

11. RESEARCH Other Treatment Options: Antihistamines Corticosteroids Interferon Chemotherapy Radiation Bone Marrow Transplants Kinase Inhibitors (Imatinib)

12. DISCUSSION ADVANCES IN THE LAST DECADE Serum Tryptase > 20ng/ml Markers such as CD2, CD25 c-kit mutations Bone Marrow Aspirations New Drug Therapy

13. Discussion Further Research More Data to support criteria and classification Better tests to accurately diagnose SM Better Effective Standardized Treatment Options Studies on what causes SM, frequency of occurrence, and, IgE and its role Clarification of Associated Clonal Hematological non-mast cell disease

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