What Are the Types of Systemic Mastocytosis?

SM Can Be Either Non-Advanced or Advanced

Systemic mastocytosis (SM) is a rare chronic blood disease that occurs when the body makes too many abnormal mast cells, a type of white blood cell that plays an important role in the body’s immune response to pathogens and allergens.

In contrast to cutaneous mastocytosis, which only affects the skin and mainly occurs in children, SM affects one or more other organs — in addition to the frequent skin involvement — and mainly occurs in adults.

The fourth edition of the World Health Organization classification divides SM into five different subtypes. While most subtypes are associated with the same non-hereditary mutation on the KIT gene, each differs in biology, symptom severity, and prognoses. “This is not a homogeneous disease,” said Cem Akin, MD, a clinical professor of allergy and immunology at University of Michigan Health in Ann Arbor.

These types break down into two different categories: non-advanced and advanced. Two of the subtypes are considered non-advanced, while the three remaining subtypes are advanced.

Indolent Systemic Mastocytosis (ISM)

ISM is the most common subtype of systemic mastocytosis, with some experts saying it could account for as many as 80% of all SM cases. This diagnosis involves a relatively low burden of mast cells and generally has no impact on life expectancy. However, symptoms of ISM, which include rashes, muscle and joint pain, and nausea, can still have a significant impact on quality of life, Dr. Akin said.

People with ISM are also at increased risk of anaphylactic shock, a potentially deadly allergic reaction. “Because they have more of the cells that cause the allergic reaction, this could be a life-threatening situation,” Dr. Akin said.

Smoldering Systemic Mastocytosis (SSM)

Unlike BMM and ISM, SSM is characterized by a higher burden of mast cells. Patients with SSM don’t experience the organ damage that occurs in advanced subtypes. However, “smoldering is kind of a transitional state,” said Jason Gotlib, MD, MS, a hematologist at the Stanford Cancer Center in Palo Alto, California. While fewer than 5% of ISM cases develop into advanced systemic mastocytosis, that proportion jumps to 18% in SSM.

Aggressive Systemic Mastocytosis (ASM)

In ASM, the accumulation of mast cells leads to organ damage - typically in the liver, gastrointestinal tract, or bone. ASM can produce a wide range of symptoms, including unexplained weight-loss, bloating, an enlarged spleen or liver and bone pain. Complications include anemia, liver disease, difficulty absorbing nutrients from food, and bone fractures.

ASM typically carries a worse prognosis than non-advanced subtypes; the typical life-expectancy after diagnosis is less than six years. Treatment for ASM focuses on reducing symptoms and the number of mast cells in the body. This can involve biologic therapies such as interferon-a, a chemotherapy called cladribine, corticosteroids, KIT inhibitors, and - rarely - bone marrow transplant.

Mast Cell Leukemia (MCL)

In MCL, the bone marrow starts producing abnormal or underdeveloped mast cells, leading to organ dysfunction. MCL is the most aggressive form of SM. Life expectancy for people with this diagnosis ranges from two months to two years.

Many of its symptoms look similar to those of the less aggressive subtypes. The most common symptoms reported were flushing, fever, fatigue, and diarrhea. It’s also common for MCL patients to experience extreme, unexplained weight loss, an enlarged spleen or liver, stomach ulcers, and internal bleeding.

This SM subtype is very rare, accounting for fewer than one percent of all mastocytosis cases. In rare instances, another SM subtype can develop into MCL. More often, it develops without any prior SM diagnosis. MCL treatment focuses on alleviating symptoms, often through anti-histamines and corticosteroids, and reducing the number of mast cells in the body, typically through chemotherapy, KIT inhibitors, and/or bone marrow transplant transplant.

Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN)

In SM-AHN, SM is associated with other forms of abnormal cell growth, particularly myeloproliferative neoplasms (MPNs). This blood cancer involves a mutation in bone marrow stem cells. SM-AHN makes up to 70-80% of all advanced SM cases.second most common subtype.

When a patient is diagnosed with SM-AHN, their doctor will help prioritize which condition needs the most immediate treatment. Occasionally, both may be treated simultaneously.