Frequency and prognostic impact of blood-circulating tumor mast cells in mastocytosis.

Circulating tumor mast cells (CTMC) have been identified in the blood of a small number of patients with advanced systemic mastocytosis (SM). However, limited data exists about their frequency and prognostic impact in patients with mast cell activation syndromes (MCAS), cutaneous and non-advanced SM. We investigated the presence of CTMC and mast cell-committed CD34+ precursors in blood of 214 patients with MCAS, cutaneous mastocytosis and SM using highly sensitive next-generation flow cytometry. CTMC were detected at progressively lower counts in almost all advanced SM (96%) and smoldering SM (100%), nearly half (45%) indolent SM cases and few (7%) bone marrow mastocytosis patients, but were systematically absent in cutaneous mastocytosis and MCAS (P<0.0001). In contrast to CTMC counts, the number of mast cell-committed CD34+ precursors progressively decreased from MCAS, cutaneous mastocytosis and bone marrow mastocytosis to indolent SM, smoldering SM and advanced SM (P<0.0001). Clinically, the presence (and number) of CTMC in blood of patients with SM in general and non-advanced SM (indolent SM and bone marrow mastocytosis) in particular was associated with more adverse features of the disease, poorer risk prognostic subgroups as defined by the International Prognostic Scoring System for advanced SM (P<0.0001) and the Global Prognostic Score for mastocytosis (P<0.0001) and a significantly shortened progression-free survival (P<0.0001) and overall survival (P=0.01). Based on our results, CTMC emerge as a novel candidate biomarker of disseminated disease in SM that is strongly associated with advanced SM and poorer prognosis in patients with indolent SM.