Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients

Abstract

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n 5 255) and without (n 5 165) skin lesions, smouldering (n 5 20), aggressive (n 5 28), associated with other hematological diseases mastocytosis (n 5 21) and mast cell leukemia (n 5 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations.

Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis

“…Systemic mastocytosis (SM) often represents a diagnostic challenge, both in the clinic where symptoms may be variable and nonspecific and in the laboratory where pathoanatomical changes may be subtle . A significant fraction of SM patients lack the characteristic dense MC infiltrates in the bone marrow (BM) . In these patients, the BM infiltration is very discrete and the SM diagnosis therefore solely based on WHO minor diagnostic criteria (referred to as “occult mastocytosis”) .…”

Improving prognostic tools in systemic mastocytosis: Insights from mutations

“…There was a gradient in mutation frequency from SM‐AHN to ASM to ISM. The low frequency of KIT D816V mutation (75%) in the current study compared to other series might not be totally unexpected owing to the use of NGS that suffers from lower sensitivity compared to ASO‐RT‐PCR techniques in the detection of very low KIT mutant allele burden. This indirectly underlines the importance of using adequate detection methods in the diagnostic path for patients suspected to have SM.…”

Myelodysplasia as assessed by multiparameter flow cytometry refines prognostic stratification provided by genotypic risk in systemic mastocytosis

“…Nevertheless, SM has an extreme heterogeneity of disease manifestations, courses and prognoses. Selected clinical findings usually characterize aggressive vs indolent variants, a distinction that drives therapeutic decisions; additional patient‐ and disease‐related variables, including advanced age, elevated beta‐2‐microglobulin and alkaline phosphatase (ALP) levels, correlate with survival …”