UK Single Institution Experience of Mastocytosis: Guy's and St Thomas' NHS Foundation Trust

Introduction: Systemic mastocytosis (SM) is a heterogeneous disorder of neoplastic mast cells ranging from an indolent to aggressive multi-system disease. We registered our UK Mastocytosis Centre of Excellence with the European Competence Network of Mastocytosis (ECNM) in 2005. Our multidisciplinary team (MDT) includes haematologists, haematopathologists, dermatologist, immunologist and molecular diagnosticians. Over 500 patients have been reviewed in our quarterly SM-MDT. We present a large single centre experience of a rare disorder. Method: We have reviewed prospective and retrospectively collected clinical data for 125 adult patients from 2009. The data captures clinical, laboratory, diagnostic results and management. Local patients with a tryptase level of >20ug/L are offered haematology review and bone marrow investigation with KIT D816V mutation analysis using digital PCR. Patients seen for a second opinion have their diagnostic material reviewed. Since 2018, next generation sequencing (NGS) based myeloid gene panels are carried out on patients with advanced SM (AdvSM). Results: Classification of mastocytosis patients: In 125 patients no gender bias was seen: 56 (44.8%) were male and 69 (55.2%) female. Median age of patients with indolent SM (ISM) was 49 years (range 22-78); and for AdvSM: (aggressive SM, SM with an associated haematological neoplasm and mast cell leukaemia) was 64years (range 5-77). The median serum tryptase level was 48.9ug/L for ISM patients (range 4-682) and 120ug/L for AdvSM patients (range 24-854). 112/125 patients had a bone marrow biopsy. 13 patients chose not to have a biopsy. 88% (110/125) of patients had a mast cell disorder. 4% (5/125) had no marrow involvement. 84% (105/125) met WHO criteria for a diagnosis of SM - Figure 1.These were sub-classified: 71/105 (67%) ISM; 2/105 (2%) smouldering SM (SSM); 3/105 (3%) aggressive SM (ASM); 2/105 (2%) mast cell leukaemia (MCL) and 27/105 (26%) SM with an associated hematologic neoplasm (SM-AHN). The most frequent associated haematological neoplasms were MPN and CMML. Lymphomas (n=3) and plasma cell dyscrasias (n=1) were seen patients. In 10/27 (37%) cases of SM-AHN the SM was the initial diagnosis with subsequent development of an AHN. In 5/27(19%) cases the AHN component preceded the SM and in 12/27 (44%) cases the 2 components were co-diagnosed. Mutation status: 24/32 patients with AdvSM were noted to be positive for an activating KIT mutation (D816V, n=23; D816L, n=1). 15/32