title: Advanced mast cell disease: an Italian Hematological Multicenter experience.
abstract: The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy. lpagano@rm.unicatt.it.
authors.forename: Livio
authors.initials: L
authors.lastname: Pagano
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.
authors.forename: Caterina Giovanna
authors.initials: CG
authors.lastname: Valentini
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.
authors.forename: Morena
authors.initials: M
authors.lastname: Caira
authors.affiliation: Istituto di Ematologia L. e A. Seragnoli, Università di Bologna, Bologna, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Rondoni
authors.affiliation: Centro Trapianti di Midollo, Ospedale S. Martino, Genova, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Van Lint
authors.affiliation: Clinica di Ematologia, Università di Udine, Udine, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.affiliation: Divisione di Ematologia, Ospedale di Alessandria, Alessandria, Italy.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Allione
authors.affiliation: Divisione di Ematologia, Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cattaneo
authors.affiliation: Divisione di Ematologia, Ospedale Niguarda Ca' Grande, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Marbello
authors.affiliation: Cattedra di Ematologia, Università di Parma, Parma, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Caramatti
authors.affiliation: Divisione di Ematologia, Ospedale S. Gerardo, Monza, Italy.
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Pogliani
authors.affiliation: Divisione di Ematologia e TMO, Policlinico di Palermo, Palermo, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Iannitto
authors.affiliation: Istituto di Ematologia, Università "La Sapienza", Rome, Italy.
authors.forename: Fiorina
authors.initials: F
authors.lastname: Giona
authors.affiliation: Divisione di Ematologia, Ospedale Cardarelli, Naples, Italy.
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Divisione di Medicina Interna ed Oncologia Medica, Università di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Invernizzi
authors.affiliation: Unità Operativa di Ematologia, Università di Firenze, Florence, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fanci
authors.affiliation: Divisione di Ematologia, Università degli Studi del Piemonte Orientale Amedeo Avogadro, Novara, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Fianchi
authors.affiliation: Divisione di Ematologia e TMO, IRCCS Ospedale Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Sanpaolo
authors.affiliation: Divisione di Ematologia, Ospedale Ca' Foncello, Treviso, Italy.
authors.forename: Pietro Maria
authors.initials: PM
authors.lastname: Stefani
authors.affiliation: Istituto di Ematologia, Università "La Sapienza", Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
authors.affiliation: Istituto di Ematologia L. e A. Seragnoli, Università di Bologna, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Istituto di Ematologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.affiliation: Centro di Riferimento Oncologico di Basilicata, Rionero in Vulnure, Potenza, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage; D001549:Benzamides; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D007558:Italy; D008099:Liver / Q000378:metabolism; D008297:Male; D008415:Mastocytosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage; D012074:Remission Induction; D012189:Retrospective Studies; D013154:Spleen / Q000378:metabolism; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit