Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management

Abstract

Overview Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra‐cutaneous organs. Diagnosis The major criterion is presence of multifocal clusters of abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. Risk stratification Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM‐AHN), and mast cell leukemia (MCL). Identification of poor‐risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical‐molecular risk models have been developed to more accurately assign prognosis in SM patients. Management ISM patients have a normal life expectancy and treatment is generally limited to anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease‐related organ dysfunction. High response rates have been seen with small‐molecule inhibitors that target mutant‐KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon‐α, although head‐to‐head comparisons are lacking. Treatment of SM‐AHN primarily targets the AHN component, if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib‐sensitive KIT mutations.

Systemic mastocytosis with chronic myelomonocytic leukemia followed by transformation into acute myeloid leukemia

“…It should be mentioned that mastocytosis is a rare part of the differential diagnosis and can be confirmed only after using the appropriate immunohistochemistry panel [11]. Interestingly, we did not observe the features typical for [20].…”

Elevated Serum Tryptase in Non-Anaphylaxis Cases: A Concise Review

“…A serum tryptase > 20 μg/L is a diagnostic criteria for systemic mastocytosis; however, values in the normal range do not reliably exclude this condition [14]. The total tryptase in mastocytosis patients is not affected by the number of α-and β-tryptase alleles [15]; though, patients with mastocytosis often have a greater elevated α-tryptase form over β-tryptase [3].…”

Hypertryptasemia and Mast Cell-Related Disorders in Severe Osteoporotic Patients

“…Diagnostic workup for the secondary causes of OP requires extensive biochemical evaluation. In this context, the assessment of serum tryptase, a mastocyte cell-specific serine protease, could be considered in order to rule out systemic mastocytosis, a rare hematological disorder generally associated with hypertryptasemia [ 4 ]. Mastocytosis comprises a heterogeneous group of disorders characterized by expansion and accumulation of neoplastic mast cells (MCs) in one or more organ systems.…”