Internal medicine

Systemic mastocytosis

Gene

Gene expression

Oncology

Chemistry

DNA methylation

Immunology

Imatinib

Midostaurin

Leukemia

Myeloid leukemia

Cladribine

Bone marrow

Decitabine

Biochemistry

Medicine

American Journal of Hematology

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 KIT D816V 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 in adults: 2019 update on diagnosis, risk stratification and management