title: Current treatment options in patients with mastocytosis: status in 2015 and future perspectives.
abstract: Mastocytosis is a term referring to a heterogeneous group of disorders characterized by abnormal mast cell (MC) accumulation in the skin and/or internal organs. In children, the disease involves mostly the skin (cutaneous mastocytosis; CM), whereas in adults, the disease is usually systemic (systemic mastocytosis; SM). Advanced SM variants with end-organ damage and reduced life expectancy have also been described, but are rare. Clinical signs and symptoms in SM result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. As a consequence, treatment of indolent SM aims primarily at the control of symptoms caused by MC mediator release. By contrast, in advanced SM, such as aggressive SM, MC leukemia, and MC sarcoma, intensive (chemo)therapy with or without allogeneic stem cell transplantation has to be considered. In addition, activating mutations in KIT (mostly KIT D816V in adults) are found in most patients with SM, so that targeted therapies aimed at blocking mutant KIT variants or/and downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies in advanced SM.
authors.affiliation: Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France.|Laboratory of Hematology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Arock
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
authors.affiliation: Clinical Hematology Department, Faculty of Medicine and AP-HP Necker-Enfants Malades, Paris Descartes University, Paris, France.|Imagine Institute, INSERM U1168, CNRS ERL 8654, National Reference Center on Mastocytosis, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D019468:Disease Management; D006801:Humans; D007167:Immunotherapy; D018836:Inflammation Mediators / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008415:Mastocytosis / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D018836:Inflammation Mediators
keywords: KIT mutations; allogeneic stem cell transplantation; antihistamines; cytoreduction; mastocytosis; surface antigens; targeted therapy; tyrosine kinase inhibitors