Lauren A. Ebbecke

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

IntroductionListed below are some of the symptoms that people with SM can experience :Rashes or Itching loss of consciousness hypotension anaphylactic reactionsosteoporosis gastrointestinal upsetsNausea or vomiting DiarrheaAnemia FlushingWheezing DizzinessReduced Blood Platelets Leukopenia

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

RESEARCHWHO 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

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

RESEARCHWHO Classification for SM

RESEARCHWHO Classification for SM continued….

Diagnosis of SM 1 major criteria and 1 minor

criteria have been met 3 minor criteria have been met

RESEARCHSystemic 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

RESEARCH

ASM, MCL, and SM-AHNMD Have a very poor prognosis (death).

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

RESEARCH Other Treatment Options:

•Antihistamines•Corticosteroids•Interferon•Chemotherapy•Radiation•Bone Marrow Transplants•Kinase Inhibitors (Imatinib)

DISCUSSION

ADVANCES IN THE LAST DECADE

• Serum Tryptase > 20ng/ml• Markers such as CD2, CD25• c-kit mutations• Bone Marrow Aspirations• New Drug Therapy

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

REFERENCESBains SN, Hsieh FH. Current Approaches to the diagnosis and treatment of systemic mastocytosis, Ann Allergy Asthma Immunol. 2010 Jan, 104(1):1-10.

de Olano DG, de la Hoz Caballer B, Nu´ n˜ ez Lo´ pez R, Sanchez Munoz L, Cuevas Augustin M, Diguez L et al. Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients with mastocytosis in Spain: a study of the Spanish network on mastocytosis (REMA). Clin Exp Allergy 2007, 37:1547–1555.

Henz, Beate M. Exploring the Mast Cell Enigma: A Personal Reflection of What Remains to Be Done. Experimental Dermatology, 2008, 17, 91-99.

Horny HP. An Unusual Clonal Disorder of Bone Marrow-Derived Hematopoietic Progenitor Cells. Am J Clin Pathol 2009, 132; 438-447. Horny H.P., Sotlar K, Valent P.. Mastocytosis: state of the art. Pathobiology. 2007, 74(2):121-32.

Horny HP, Sotlar K, Valent P. Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy Specimens: a reviwe. Pathobiology. 2010;77(4):169-80. Epub 2010 Jul 7.

Lim KH, Tefferi A, Lasho TL, Finke C, Patnaik M, Butterfield JH, McClure RF, Li CY, Pardanani A. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009, 113:5727–36.

Orfao, Alberto, Andrés C. Garcia-Montero, Laura Sanchez and Luis Escribano. Recent advances in the understanding of mastocytosis: the role of KIT mutations. British Journal of Haematology. Volume 138, Issue 1, July 2007, Pages: 12–30.

REFERENCESPardanani A. and A. Tefferi , A Critical reappraisal of treatment response criteria in systemic mastocytosis and a proposal for revisions. European Journal of Haematology. Volume 84, Issue 5, May 2010, Pages: 371–378.

Quintas-Cardama A, Aribi A, Cortes J, Giles F J, Kantarjian H, and Verstovsek S, Novel Approaches in the Treatment of Systemic Mastocytosis. Cancer 2006, 107:1429–39.

Valent, Peter, Cem Akin, Wolfgang R. Sperr, Hans-P. Horny, Michel Arock, Klaus Lechner, John M. Bennett and Dean D. Metcalfe, Diagnostic and Treatment of Systemic Mastocytosis: State of The Art. British Journal of Haematology, Volume 122, Issue 5, September 2003, Pages: 695–717.

Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nunez R, Akin C, Sotlar K, Sperr WR, Wolff K. Brunning RD, Parwaresch RM, Austen KF, Lennett K, Metcalfe DD, Vardiman JW, Bennett JM. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001 Jul, 25(7):603-25

Peter Valenta Luis Escribanob Reza M. Parwareschc Verena Schemmeld Lawrence B. Schwartze Karl Sotlarf Wolfgang R. Sperra Hans-Peter Horny. Recent Advances in Mastocytosis Research: Summary of Vienna Mastocytosis Meeting 1998. Int Arch Allergy Immunol 1999;120:1–7.

Valent, P., Akin, C., Sperr, W.R., Mayerhofer, M., Fodinger, M., Fritsche-Polanz, R., Sotlar, K., Escribano, L., Arock, M., Horny, H.P. & Metcalfe, D.D. (2005) Mastocytosis: pathology, genetics, and current options for therapy. Leukemia and Lymphoma, 46: 35–48.

REFERENCESYin C. C., L. J. Medeiros, C. E. Bueso-Ramos. Recent advances in the diagnosis and classification of myeloid neoplasms – comments on the 2008 WHO Classification. International Journal of Laboratory Hematology, 2010, 32: 461–476.

Webb T, Md,’ Chin-Yang Li, Md,T And Lung T. Yam, Mds. Systemic Mast Cell Disease: A Clinical and Hematopathologic Study of 26 Cases. Cancer 1982, 49:927-938.

http://www.tmsforacure.org