Abstract
Background
Systemic mastocytosis (SM) is a spectrum of hematologic disorders characterized by accumulation of atypical mast cells (MCs) in extracutaneous organs. SM with an associated hematologic neoplasm (SM-AHN), the most frequent subtype of advanced SM, is predominantly associated with myeloid neoplasms, consistent with shared clonal architecture. Because of its rarity and heterogeneity, robust outcome data aligned with contemporary classifications are needed to inform risk stratification.Methods
We analyzed the 10th data wave of the European Competence Network on Mastocytosis registry (34 European centers and 1 US center). SM and AHN diagnoses followed the 2022 World Health Organization classification. Baseline characteristics and overall survival (OS) were compared between patients with myeloid SM-AHN and SM without AHN (SM-no-AHN). Within SM-AHN, outcomes were analyzed by SM component (advanced: aggressive SM [ASM] or MC leukemia [MCL] vs. non-advanced: bone marrow mastocytosis, indolent SM, or smoldering SM) and AHN subtype.Results
Among 3,925 patients with SM, 467 (11.9%) had myeloid SM-AHN. Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) were the most frequent AHN category (41.1%), with chronic myelomonocytic leukemia as the most common subtype (29.6%). Compared with SM-no-AHN, SM-AHN patients were older, more often male, and less frequently had skin involvement. The SM component was advanced in 55.0% of SM-AHN versus 5.8% of SM-no-AHN (p Conclusions
SM-AHN is associated with reduced survival compared with SM without AHN across SM subtypes. Outcomes in SM-AHN are driven primarily by the aggressiveness of the mastocytosis component, supporting recognition and classification of SM in patients with concomitant myeloid neoplasms, given approved KIT-targeted tyrosine kinase inhibitors for advanced SM.