What is mastocytosis (Mast Cell Disorder)?

From the Guidelines

Mastocytosis patients should be managed by a multidisciplinary team approach, preferably in specialized medical centers with expertise in the treatment of patients with mast cell disorders, as this approach has significantly improved the diagnosis and treatment of systemic mastocytosis 1.

Diagnosis and Management

The management of patients with mastocytosis requires a comprehensive approach, involving dermatologists, hematologists, gastroenterologists, pathologists, and allergists/immunologists. The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis 1.

• Treatment depends on the type and severity of the disease, but typically includes:

• Antihistamines like cetirizine (10mg daily) or fexofenadine (180mg daily) to control symptoms such as itching, flushing, and gastrointestinal distress.
• H2 blockers like ranitidine (150mg twice daily) may be added to manage gastric acid production.
• Mast cell stabilizers such as cromolyn sodium (200mg four times daily) can help prevent mast cell degranulation.

• Patients should avoid known triggers like alcohol, extreme temperatures, certain medications (NSAIDs, opioids), and physical stress.
• Epinephrine auto-injectors should be carried by patients at risk for anaphylaxis.

Advanced Systemic Mastocytosis

For advanced systemic mastocytosis, tyrosine kinase inhibitors like midostaurin (100mg twice daily) may be prescribed, as recommended by the NCCN clinical practice guidelines in oncology 1.

• Treatment considerations for aggressive systemic mastocytosis include midostaurin, cladribine, imatinib, and interferons.
• Patients with advanced SM should be counseled regarding signs and symptoms of disease and potential triggers of mast cell activation.

Indolent Systemic Mastocytosis and Smoldering Systemic Mastocytosis

For indolent systemic mastocytosis and smoldering systemic mastocytosis, treatment typically involves managing mast cell activation symptoms with anti-mediator drug therapy, as well as regular monitoring and reassessment of symptom burden and quality of life 1.

• Patients with symptomatic ISM or SSM should be managed with anti-mediator drug therapy and regular monitoring of labs and clinical issues.
• DEXA scans should be performed every 1-3 years for patients with osteopenia or osteoporosis.

From the Research

Definition and Classification of Mastocytosis

• Mastocytosis is a unique and rare neoplasm defined by abnormal expansion and accumulation of clonal mast cells (MCs) in one or multiple organ systems 2.
• Systemic mastocytosis (SM) is classified into indolent SM (ISM), smoldering SM (SSM), SM with an associated hematologic non-MC-lineage disease (SM-AHNMD), aggressive SM (ASM), and MC leukemia (MCL) 2.

Clinical Symptoms and Treatment

• Clinical symptoms in mastocytosis result from the release of proinflammatory and vasoactive mediators from MCs, and SM-induced organ damage 2.
• Therapy of SM has to be adjusted to the individual patient and the SM category: in those with ISM and SSM, the goal is to control mediator secretion and/or mediator effects, to keep concomitant allergies under control, and to counteract osteoporosis 2.
• In advanced SM (ASM, MCL, and SM-AHNMD), anti-neoplastic drugs are prescribed to suppress MC expansion and/or to keep AHNMD cells under control 2.
• Pharmacotherapy of mastocytosis is aimed at the control of symptoms caused by MC mediator release, treatment of comorbidities and cytoreductive therapies in advanced variants 3.

Diagnosis and Risk Stratification

• The major criterion for diagnosing systemic mastocytosis is the presence of multifocal clusters of spindled MC in the bone marrow 4, 5.
• Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation 4, 5.
• Identification of poor-risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification 4, 5.

Treatment Options

• High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational) 4, 5.
• Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking 4, 5.
• Allogeneic stem cell transplant can be considered in patients with relapsed/refractory advanced SM or in those with SM-AHN 4, 5.