, mois dans la population ASM, 15.4 mois dans la population ASM-AHD et 30,5 mois dans la population MCL

, Considérant les sous-types histologiques : -16 patients sur 17 présentant une ASM (94%) ont répondu

, Un patient (6%) présentait une maladie progressive, aucun n'était en maladie stable. -19 patients sur 25 présentant une ASM-AHD (76%) ont répondu, dont 10 patients (40%) avec une RP et 9 patients (36%) avec une IC. 2 patients (8%) présentaient une maladie progressive, avec une RP et 9 patients (53%) avec une IC

, -2 patients sur 4 présentant une MCL (50%) ont répondu, dont un patient (25%) avec une RP et un patient (25%) avec une IC. 2 patients (50%) présentaient une maladie progressive

, patients (20%) ont présenté une rechute de la maladie, 3 (18%) dans la population ASM et 6 (24%) dans la population ASM-AHD, avec des délais de rechute entre 3 et 38 mois

, Au sein de la population ASM-AHD, 6 patients sur 25 (24%) ont présenté une acutisation de l'hémopathie non mastocytaire

, Le tableau X et la figure IV résument ces données générales concernant la réponse thérapeutique

K. Brockow and D. D. Metcalfe, Mastocytosis". Curr Opin Allergy Clin Immunol, vol.1, issue.5, pp.449-54, 2001.

J. J. Van-doormaal, S. Arends, K. L. Brunekreeft, V. B. Van-der-wal, and J. Sietsma, Prevalence of indolent systemic mastocytosis in a Dutch region, J Allergy Clin Immunol, vol.131, issue.5, pp.1429-1460, 2013.

B. V. Kettelhut and D. D. Metcalfe, Pediatric mastocytosis, Ann Allergy, vol.73, issue.3, pp.197-202, 1994.

K. H. Lim, A. Tefferi, T. L. Lasho, C. Finke, and M. Patnaik, Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors, Blood, vol.113, issue.23, pp.5727-5763, 2009.

H. P. Horny, C. Akin, D. D. Metcalfe, L. Escribano, and J. M. Bennett, , 2008.

;. Mastocytosis, S. H. Swerdlow, E. Campo, N. L. Harris, E. S. Jaffe et al., World Health Organization (WHO) Classification of Tumours, pp.54-63

P. Valent, H. P. Horny, L. Escribano, B. J. Longley, and C. Y. Li, Diagnostic criteria and classification of mastocytosis: a consensus proposal, Leuk Res, vol.25, issue.7, pp.603-628, 2001.

P. Valent, C. Akin, L. Escribano, M. Födinger, K. Hartmann et al., Standards and Standardization in Mastocytosis: Consensus Statements on Diagnostics, Treatment Recommendations and Response Criteria, European Journal of Clinical Investigation, vol.37, issue.6, pp.435-53, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00152499

A. Pardanani, K. H. Lim, T. L. Lasho, C. M. Finke, and R. F. Mcclure, WHO subvariants of indolent mastocytosis: clinical details and prognostic evaluation in 159 consecutive adults, Blood, vol.115, issue.1, pp.150-151, 2010.

W. D. Travis, C. Y. Li, L. T. Yam, E. J. Bergstralh, and R. G. Swee, Significance of Systemic Mast Cell Disease with Associated Hematologic Disorders, Cancer, vol.62, issue.5, pp.965-72, 1988.

H. Horny, K. Sotlar, W. R. Sperr, and P. Valent, Systemic Mastocytosis with Associated Clonal Haematological Non-Mast Cell Lineage Diseases: A Histopathological Challenge, Journal of Clinical Pathology, vol.57, issue.6, pp.604-612, 2004.

A. Yavuz, P. E. Selim, S. Lipsky, D. D. Yavuz, C. Metcalfe et al., Evidence for the Involvement of a Hematopoietic Progenitor Cell in Systemic Mastocytosis from Single-Cell Analysis of Mutations in the c-Kit Gene, Blood, vol.100, issue.2, pp.661-65, 2002.

K. Sotlar, S. Colak, A. Bache, S. Berezowska, M. Krokowski et al., Variable Presence of KITD816V in Clonal Haematological Non-Mast Cell Lineage Diseases Associated with Systemic Mastocytosis (SM-AHNMD), The Journal of Pathology, vol.220, issue.5, pp.586-95, 2010.

M. Jawhar, J. Schwaab, S. Schnittger, K. Sotlar, H. Horny et al., Molecular Profiling of Myeloid Progenitor Cells in Multi-Mutated Advanced Systemic Mastocytosis Identifies KIT D816V as a Distinct and Late Event, Leukemia, vol.29, issue.5, pp.1115-1137, 2015.

C. Ustun, M. Arock, C. Hanneke, A. Kluin-nelemans, W. R. Reiter et al., Advanced Systemic Mastocytosis: From Molecular and Genetic Progress to Clinical Practice, Haematologica, vol.101, issue.10, pp.1133-1176, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01478829

J. Grootens, J. S. Ungerstedt, G. Nilsson, and J. S. Dahlin, Deciphering the Differentiation Trajectory from Hematopoietic Stem Cells to Mast Cells, Blood Advances, vol.2, issue.17, pp.2273-81, 2018.

A. Pardanani, K. Lim, T. L. Lasho, C. Finke, R. F. Mcclure et al., Prognostically Relevant Breakdown of 123 Patients with Systemic Mastocytosis Associated with Other Myeloid Malignancies, Blood, vol.114, issue.18, pp.3769-72, 2009.

A. Pardanani, Update on Diagnosis, Risk Stratification, and Management, American Journal of Hematology, vol.90, issue.3, pp.250-62, 2015.

M. M. Stoecker and E. Wang, Systemic mastocytosis with associated clonal hematologic nonmast cell lineage disease: a clinicopathologic review, Arch Pathol Lab Med, vol.136, issue.7, pp.832-840, 2012.

M. Arock and P. Valent, Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives, Expert Rev Hematol, vol.3, issue.4, pp.497-516, 2010.

S. Georgin-lavialle, L. Lhermitte, P. Dubreuil, M. O. Chandesris, and O. Hermine, Mast cell leukemia, Blood, vol.121, issue.8, pp.1285-95, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00844934

H. P. Horny, M. Krokowski, A. C. Feller, G. Hintze, and K. Sotlar, Aleukemic mast cell leukemia (formerly: malignant mastocytosis): an extremely rare form of leukemia. A case report and simultaneously a contribution to revised classification of mastocytosis, Wien Klin Wochenschr, vol.114, issue.5-6, pp.222-230, 2002.

A. R. Arredondo, J. Gotlib, L. Shier, B. Medeiros, and K. Wong, Myelomastocytic leukemia versus mast cell leukemia versus systemic mastocytosis associated with acute myeloid leukemia: a diagnostic challenge, Am J Hematol, vol.85, issue.8, pp.600-606, 2010.

P. Valent, W. R. Sperr, and C. Akin, How I treat patients with advanced systemic mastocytosis, Blood, vol.116, issue.26, pp.5812-5819, 2010.

M. Jawhar, J. Schwaab, M. Meggendorfer, N. Naumann, H. Horny et al., The Clinical and Molecular Diversity of Mast Cell Leukemia with or without Associated Hematologic Neoplasm, Haematologica, vol.102, issue.6, pp.1035-1078, 2017.

P. Valent, K. Sotlar, W. R. Sperr, L. Escribano, and S. Yavuz, Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal, Ann Oncol, vol.25, issue.9, pp.1691-700, 2014.

M. Castells, Mast cell mediators in allergic inflammation and mastocytosis, Immunol Allergy Clin North Am, vol.26, issue.3, pp.465-85, 2006.

I. R. Reisberg and S. Oyakawa, Mastocytosis with malabsorption, myelofibrosis, and massive ascites, Am J Gastroenterol, vol.82, pp.54-60, 1987.

C. Lidor, B. Frisch, D. Gazit, R. Gepstein, T. Hallel et al., Osteoporosis as the sole presentation of bone marrow mastocytosis, J Bone Miner Res, vol.5, pp.871-877, 1990.

D. S. Moura, S. Georgin-lavialle, R. Gaillard, and O. Hermine, Neuropsychological features of adult mastocytosis, Immunol Allergy Clin North Am, vol.34, issue.2, pp.407-429, 2014.

K. Sotlar, H. P. Horny, and I. Simonitsch, CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens, Am J Surg Pathol, vol.28, pp.1319-1325, 2004.

M. Jawhar, J. Schwaab, H. Horny, K. Sotlar, N. Naumann et al., Impact of Centralized Evaluation of Bone Marrow Histology in Systemic Mastocytosis, European Journal of Clinical Investigation, vol.46, issue.5, pp.392-97, 2016.

K. Sotlar, S. Cerny-reiterer, K. Petat-dutter, H. Hessel, S. Berezowska et al., Aberrant Expression of CD30 in Neoplastic Mast Cells in High-Grade Mastocytosis, Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, vol.24, issue.4, pp.585-95, 2011.

L. Escribano, B. Diaz-agustin, A. López, R. N. López, A. García-montero et al., Immunophenotypic Analysis of Mast Cells in Mastocytosis: When and How to Do It. Proposals of the Spanish Network on Mastocytosis (REMA), Clinical Cytometry, vol.58, issue.1, pp.1-8, 2004.

H. Nagata, A. S. Worobec, C. K. Oh, B. A. Chowdhury, and S. Tannenbaum, Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder, Proc Natl Acad Sci U S A, vol.92, issue.23, pp.10560-10564, 1995.

T. Furitsu, T. Tsujimura, T. Tono, H. Ikeda, and H. Kitayama, Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product, J Clin Invest, vol.92, issue.4, pp.1736-1780, 1993.

F. Noack, K. Sotlar, M. Notter, E. Thiel, and P. Valent, Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation D816V, Leuk Lymphoma, vol.45, issue.11, pp.2295-302, 2004.

A. C. Garcia-montero, M. Jara-acevedo, C. Teodosio, M. L. Sanchez, R. Nunez et al., KIT Mutation in Mast Cells and Other Bone Marrow Hematopoietic Cell Lineages in Systemic Mast Cell Disorders: A Prospective Study of the Spanish Network on Mastocytosis (REMA) in a Series of 113 Patients, Blood, vol.108, issue.7, pp.2366-72, 2006.

B. Wasag, M. Niedoszytko, A. Piskorz, M. Lange, and J. Renke, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis, Exp Hematol, vol.39, issue.8, pp.859-65, 2011.

T. M. Wilson, I. Maric, O. Simakova, Y. Bai, and E. C. Chan, Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis, Haematologica, vol.96, issue.3, pp.459-63, 2011.

E. Soucie, K. Hanssens, T. Mercher, S. Georgin-lavialle, and G. Damaj, In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells, Blood, vol.6, issue.24, pp.4846-4855, 2012.

. Damaj, M. Gandhi, O. Joris, K. Chandesris, E. Hanssens et al., ASXL1 but Not TET2 Mutations Adversely Impact Overall Survival of Patients Suffering Systemic Mastocytosis with Associated Clonal Hematologic Non-Mast-Cell Diseases, PloS One, vol.9, issue.1, p.85362, 2014.

K. Hanssens, F. Brenet, J. Agopian, S. Georgin-lavialle, and G. Damaj, SRSF2-p95 hotspot mutation is highly associated with advanced forms of mastocytosis and mutations in epigenetic regulator genes, Haematologica, vol.99, issue.5, pp.830-835, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01325368

M. Jawhar, J. Schwaab, S. Schnittger, M. Meggendorfer, M. Pfirrmann et al., Additional Mutations in SRSF2, ASXL1 And/Or RUNX1 Identify a High-Risk Group of Patients with KIT D816V(+) Advanced Systemic Mastocytosis, Leukemia, vol.30, issue.1, pp.136-179, 2016.

P. Valent, Mastocytosis: a paradigmatic example of a rare disease with complex biology and pathology, Am J Cancer Res, vol.3, issue.2, pp.159-72, 2013.

L. B. Schwartz, D. D. Metcalfe, J. S. Miller, H. Earl, and T. Sullivan, Tryptase Levels as an Indicator of Mast-Cell Activation in Systemic Anaphylaxis and Mastocytosis, The New England Journal of Medicine, vol.316, issue.26, pp.1622-1648, 1987.

L. B. Schwartz, Diagnostic Value of Tryptase in Anaphylaxis and Mastocytosis, Immunology and Allergy Clinics of North America, vol.26, issue.3, pp.451-63, 2006.

P. Valent, H. P. Horny, L. Escribano, B. J. Longley, C. Y. Li et al., Diagnostic Criteria and Classification of Mastocytosis: A Consensus Proposal, Leukemia Research, vol.25, issue.7, pp.603-628, 2001.

P. Valent, C. Akin, L. Escribano, M. Födinger, K. Hartmann et al., Standards and Standardization in Mastocytosis: Consensus Statements on Diagnostics, Treatment Recommendations and Response Criteria, European Journal of Clinical Investigation, vol.37, issue.6, pp.435-53, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00152499

A. Pardanani and A. Tefferi, A Critical Reappraisal of Treatment Response Criteria in Systemic Mastocytosis and a Proposal for Revisions, European Journal of Haematology, vol.84, issue.5, pp.371-78, 2010.

J. Gotlib, A. Pardanani, C. Akin, A. Reiter, T. George et al., International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) Consensus Response Criteria in Advanced Systemic Mastocytosis, Blood, vol.121, issue.13, pp.2393-2401, 2013.

C. Ustun, A. Reiter, B. L. Scott, R. Nakamura, G. Damaj et al., Hematopoietic Stem-Cell Transplantation for Advanced Systemic Mastocytosis, Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, vol.32, issue.29, pp.3264-74, 2014.

M. Arock, C. Akin, O. Hermine, and P. Valent, Current treatment options in patients with mastocytosis: status in 2015 and future perspectives, Eur J Haematol, vol.94, issue.6, pp.474-90, 2015.

D. D. Metcalfe, The treatment of mastocytosis: an overview, J Invest Dermatol, vol.96, issue.3, pp.55-56, 1991.

M. Laroche, C. Livideanu, C. Paul, and A. Cantagrel, Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis, Am J Med, vol.124, issue.8, pp.776-784, 2011.

A. Tefferi, S. Verstovsek, and A. Pardanani, How we diagnose and treat WHO-defined systemic mastocytosis in adults, Haematologica, vol.93, issue.1, pp.6-9, 2008.

U. Lippert and B. M. Henz, Long-Term Effect of Interferon Alpha Treatment in Mastocytosis, The British Journal of Dermatology, vol.134, issue.6, pp.1164-65, 1996.

K. H. Lim, A. Pardanani, J. H. Butterfield, C. Li, and A. Tefferi, Cytoreductive Therapy in 108 Adults with Systemic Mastocytosis: Outcome Analysis and Response Prediction during Treatment with Interferon-Alpha, Hydroxyurea, Imatinib Mesylate or 2-Chlorodeoxyadenosine, American Journal of Hematology, vol.84, issue.12, pp.790-94, 2009.

S. Barete, O. Lortholary, G. Damaj, I. Hirsch, M. O. Chandesris et al., Long-Term Efficacy and Safety of Cladribine (2-CdA) in Adult Patients with Mastocytosis, Blood, vol.126, issue.8, pp.1009-1016, 2015.

P. Valent, C. Akin, W. R. Sperr, M. Mayerhofer, and M. Födinger, Mastocytosis: pathology, genetics, and current opinions for the therapy, Leuk Lymphoma, vol.46, issue.1, pp.35-48, 2005.

L. Pagano, C. G. Valentini, M. Caira, M. Rondoni, M. T. Van-lint et al., Advanced Mast Cell Disease: An Italian Hematological Multicenter Experience, International Journal of Hematology, vol.88, issue.5, pp.483-88, 2008.

K. A. Hahn, G. Ogilvie, G. Oglivie, T. Rusk, P. Devauchelle et al., Masitinib Is Safe and Effective for the Treatment of Canine Mast Cell Tumors, Journal of Veterinary Internal Medicine, vol.22, issue.6, pp.1301-1310, 2008.

P. Dubreuil, S. Letard, M. Ciufolini, L. Gros, and M. Humbert, Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting, PLoS One, vol.4, issue.9, p.7258, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00423392

O. Lortholary, M. O. Chandesris, C. B. Livideanu, C. Paul, G. Guillet et al., Masitinib for Treatment of Severely Symptomatic Indolent Systemic Mastocytosis: A Randomised, Placebo-Controlled, Phase 3 Study, Lancet, vol.389, issue.10069, pp.612-632, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01787376

J. Gotlib, C. Hanneke, T. I. Kluin-nelemans, C. George, K. Akin et al., Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis, The New England Journal of Medicine, vol.374, issue.26, pp.2530-2571, 2016.

D. J. Deangelo, T. I. George, A. Linder, C. Langford, C. Perkins et al., Efficacy and Safety of Midostaurin in Patients with Advanced Systemic Mastocytosis: 10-Year Median Follow-up of a Phase II Trial, Leukemia, vol.32, issue.2, pp.470-78, 2018.

M. W. Deininger, J. Gotlib, and W. A. Robinson, BLU-285), a selective KIT inhibitor, is associated with high response rate and tolerable safety profile in advanced systemic mastocytosis: results from a phase 1 study, EHA Annual Meeting, 2018.