In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related
factors determining the outcome in SM are largely unknown. Methods: We examined the
impact of sex on the clinical features, progression-free survival (PFS), and overall
survival (OS) in 3403 patients with mastocytosis collected in the registry of the
European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and
molecular genetic aberrations on sex differences was analyzed in a subset of patients.
Results: Of all patients enrolled, 55.3% were females. However, a male predominance
was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated
hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male:
23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs.
female: 86%, p = 0.001) was less frequent in males. In all patients together, OS (p
< 0.0001) was significantly inferior in males, and also within the WHO sub-categories
indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly (p = 0.0002) worse
in males when all patients were grouped together; due to low numbers of events, this
significance persisted only in the subcategory smoldering SM. Finally, prognostically
relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations
(SRSF2/ASXLI/RUNXI profile; 63% vs. 40%, p = 0.003) were more frequently present in
males. Conclusions: Male sex has a major impact on clinical features, disease progression,
and survival in mastocytosis. Male patients have an inferior survival, which seems
related to the fact that they more frequently develop a multi-mutated AdvSM associated
with a high-risk molecular background.
