Systemic Mastocytosis. A GIMEMA Multicenter Survey.
Authors: Pagano Livio , Valentini Caterina Giovanna , Musto Pellegrino , Caira Morena , Rondoni Michela , Van Lint Maria Teresa , Candoni Anna , Martinelli Giovanni , Gatto Simona , Cattaneo Chiara , Marbello Laura , Caramatti Cecilia , Castagnola Carlo , Pogliani Enrico Maria , Mitra Maria Enza , Giona Fiorina , Fanci Rossella , Fianchi Luana , Sanpaolo Grazia , Pulsoni Alessandro , Leone Giuseppe 
Published: April 2020

Abstract
To evaluate clinical and biological features, treatments and outcome of patients(pts) with Systemic Mastocytosis(SM). A retrospective study (1995–2006) about pts with SM admitted in 14 Italian hematology divisions in tertiary cares or university hospitals.
30 cases of SM were collected(median age 62 y.o.; M/F 14/16) and classified according to the WHO criteria: Mast Cell Leukemia in 14 pts, Aggressive SM in 12 and Indolent in 3; the remaining one had SM with associated clonal non-mast cell-lineage hematologic disease. Skin was the principal extramedullary organ involved (19 pts) followed by spleen(15), liver(13), and cardiovascular system(12). Molecular biology studies were performed in 22 pts: 15 showed the c-kit point mutation D816V; in another patient a different c-kit mutation was found while in 3 pts additional gene defects and karyotype abnormalities were recognized. Treatments were heterogeneous, and the same patient could have received different therapies after failure of the previous one. Imatinib(400 mg/day) was used in 17 pts (11 as first line therapy, 5 and 1 as second and third line respectively); interferon-alpha(3×3 MU s.c. weekly) was employed in 7 patients(4 as first line therapy, 2 as second and 1 as third line); 2-CDA(0.14 mg/kg) was administered in 3 pts(1 as first, 1 as second and 1 as third line therapy); 2 patients underwent HSCT as second and third line respectively.
Data about response to treatment are reported in the table.
The overall response rate to imatinib was of 30%, registering 1 complete remission(CR) and 4 partial remissions. All but one responsive patients did not present c-kit point mutation.
Three pts(10%) died for progression of SM; a fourth patient in CR died for accidental causes. The actuarial Kaplan-Meier curve at 10 years showed an overall-survival of 87%.
Conclusions: SM is a rare disease, characterized by severe and life-threatening mediator-related symptoms but with a low mortality rate. D816V c-kit mutation is frequent and associated with resistance against imatinib: only 1 patient showed a CR. Of note 2-CDA has shown interesting clinical response: all 3 treated pts showed a clinical improvement. Because of the rarity of SM, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies; it is possible that new tyrosine kinase inhibitors could allow to achieve clinical and molecular remission of disease, crossing resistence to imatinib due to c-kit mutation, in order to improve above all quoad valitudinem prognosis of these pts.
Response to treatments. DRUGS CR PR Stable Unrespons. N.E. TOTAL Imatinib 1 4 5 3 4 17 INF-alpha 0 1 1 5 0 7 2-CDA 0 3 0 0 0 3 Conventional CTX 0 1 2 4 1 8 Allo-HSCT 2 0 0 0 0 2 Wait & Watch 0 0 6 2 0 8