title: Aggressive systemic mastocytosis and related mast cell disorders: current treatment options and proposed response criteria.
abstract: Aggressive systemic mastocytosis (ASM) is a clonal mast cell disease characterized by progressive growth of neoplastic cells in diverse organs leading to organopathy. The organ-systems most frequently affected are the bone marrow, skeletal system, liver, spleen, and the gastrointestinal tract. Respective clinical findings (so called C-Findings) include cytopenias, osteolysis (or osteoporosis) with pathologic fractures, hepatosplenomegaly with impaired liver function and ascites, and malabsorption. During the past decade several treatment strategies for ASM have been proposed. One promising approach may be combination treatment with interferon-alpha (IFN-alpha) and glucocorticoids. This concept has been based on the notion that systemic mastocytosis involves multilineage hematopoietic progenitors indicating a relationship with myeloproliferative disorders. However, relatively little is known about the quality of responses to IFN-alpha in ASM and the actual response rates. This may be due in part to the fact that disease criteria for ASM have only recently been established, and no response criteria are available. In the current article, we propose surrogate markers and treatment response criteria for patients with ASM. In addition, we have applied these criteria retrospectively to ASM patients described in the available literature. In these analyses, the calculated rate of major response (=complete resolution of C-Findings) in patients treated with IFN-alpha (with or without additional glucocorticoids) amounts to approximately 21%. This confirms clinical activity in some patients for this drug-combination, but also points to the need to search for more effective strategies in the treatment of patients with aggressive mast cell disorders.
authors.affiliation: Department of Internal Medicine I, Division of Hematology & Hemostaseology, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. peter.valent@akh-wien.ac.at
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Luis
authors.initials: L
authors.lastname: Escribano
authors.forename: Michel
authors.initials: M
authors.lastname: Arock
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horny
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D034721:Mastocytosis, Systemic / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D016898:Interferon-alpha