Advanced systemic mastocytosis (advSM) is a rare and serious form of systemic mastocytosis, a blood disorder that involves the overproduction of mast cells. Mast cells are a type of white blood cell normally involved in allergic reactions and immune defense that release histamine and other chemicals to help fight infections and respond to allergens.

There are three types of advanced systemic mastocytosis.

SM With Associated Hematologic Neoplasm (SM-AHN)

Aggressive Systemic Mastocytosis (ASM)

Mast Cell Leukemia (MCL)

The goal of treatment in people with advanced systemic mastocytosis is to control symptoms, mitigate organ damage, improve quality of life, and extend a person’s life.

“Higher-intensity therapies are needed, because we’re not only trying to manage symptoms, we’re actually trying to use therapies that kill off the mast cells and potentially restore organ function,” says Jason Gotlib, MD, a professor of hematology at Stanford University School of Medicine and a hematologist at Stanford Health Care, both in Stanford, California.

Before starting or changing any treatment plan, it is crucial to consult with your healthcare provider. Advanced systemic mastocytosis is a complex condition, and treatment approaches vary depending on the subtype and the severity of the disease.

Treatment for advanced systemic mastocytosis depends on the subtype as well as the specific symptoms and disease progression of each person.

Tyrosine Kinase Inhibitors (TKIs)

In advanced forms of systemic mastocytosis, such as aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL), drugs known as tyrosine kinase inhibitors (TKIs) may be prescribed.

These drugs work by inhibiting the tyrosine kinase activity of the KIT protein.

• Avapritinib (Ayvakit) is the primary TKI used, because it specifically targets the KIT D816V mutation, which is found in most people with advanced systemic mastocytosis.

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• Midostaurin (Rydapt), a less specific multikinase TKI, has been shown to improve survival and reduce symptoms in patients with aggressive systemic mastocytosis.

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• Imatinib mesylate (Gleevec) may be helpful for types of systemic mastocytosis with certain non-D816V KIT mutations.

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Immunomodulators

Chemotherapy

In people with aggressive systemic mastocytosis or mast cell leukemia, chemotherapy may be necessary. This type of treatment can work through various mechanisms of action, such as damaging the DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) in cancer cells and interfering with their ability to grow or multiply.

Symptom Management

• Antihistamines to relieve itching, hives, and gastrointestinal discomfort caused by the release of histamine
• Leukotriene modifiers, such as montelukast, to control skin symptoms
• Bisphosphonates to treat osteoporosis
• Corticosteroids to reduce inflammation and control symptoms, especially in more severe cases
• Pain medication, both over-the-counter and prescription, to treat pain
• Proton pump inhibitors to help with peptic ulcer disease that can occur with systemic mastocytosis
• Cromolyn sodium to relieve abdominal pain and diarrhea
• Epinephrine to treat anaphylaxis
• Monoclonal antibodies, particularly omalizumab, to treat recurrent anaphylaxis or anaphylaxis that doesn’t respond to other treatments

Depending on a person’s age and how they’ve responded to treatments, stem cell transplantation may be an option. Less invasive than surgery, the procedure is more like a blood transfusion.

Hematopoietic stem cell transplantation (ΗCT) is a medical procedure that involves replacing damaged or diseased blood-forming cells in the body with healthy ones. The treatment is typically used to treat blood disorders and certain blood cancers.

The type of stem cell transplant used in advanced systemic mastocytosis is called allogeneic hematopoietic stem cell transplantation. In this type of HCT, the blood-forming cells come from another person (a donor) rather than from the patient themselves (a so-called autologous stem cell transplant). The donor is usually someone who is a close match genetically, like a family member, although an unrelated donor from a registry can sometimes be used.

Allogeneic HCT comes with risks. The body needs time to adjust to the donor cells, and sometimes the immune system attacks the new cells, called graft-versus-host disease (GVHD), which is a serious side effect.

Surgery is not a treatment option for advanced systemic mastocytosis, though in some cases, surgery may be necessary to manage complications from organ damage caused by the disorder.

“Because advanced systemic mastocytosis is so uncommon, it’s important to find a physician who is comfortable managing this condition,” says Nikolai Podoltsev, MD, PhD, an associate professor of internal medicine (hematology) and the clinical director of malignant hematology at Yale School of Medicine in New Haven, Connecticut.

“Find a Center of Excellence and a physician who is interested in management of these diseases,” he says.

The Mast Cell Disease Society offers an online tool to help you find a Center of Excellence in your area.

Clinical trials for blood cancers may be another way to have access to the best care and medications available.

Medications are essential in managing advanced systemic mastocytosis. But lifestyle changes can contribute to symptom management and improve overall quality of life.

Avoid Triggers

Mast cell activation can be triggered by various factors, such as certain foods, environmental allergens, and stress. Identifying and avoiding these triggers can help reduce the frequency of symptoms.

But that’s a strategy that’s more effective in people whose systemic mastocytosis hasn’t become advanced disease, says Dr. Podoltsev.

“In advanced systemic mastocytosis, the triggers are less important, because there are so many mast cells that they begin causing aggressive systemic symptoms and organ damage,” he says.

When that’s happening, an allergic reaction isn’t what’s triggering the most severe symptoms, he explains.

Stress Management

Stress can exacerbate symptoms in people with advanced systemic mastocytosis.

“If you want to try practices like yoga, meditation, or acupuncture, they may help with quality of life, provided your healthcare team approves,” says Dr. Gotlib.

Advanced systemic mastocytosis can be emotionally challenging, especially when symptoms like pain or fatigue are persistent.

“Depression or other mood disorders aren’t uncommon with advanced systemic mastocytosis. They have what is basically a rare orphan hematologic disease that’s very uncommon, and it’s not easy to find specialists,” says Gotlib.

This can be a chronic, debilitating, painful condition with very significant impacts on quality of life, he says.

“People often have no appetite, lose weight, and have fatigue along with all the other complications that can come with the disease,” says Gotlib.

People with advanced systemic mastocytosis should discuss any pain or mood issues with their healthcare team so that they can get the treatment they need to have the best quality of life possible, says Gotlib.

Support groups, both in-person and online, provide a sense of community and can be a valuable resource for coping strategies, emotional support, and information about new treatments. The Leukemia and Lymphoma Society has an online tool to locate support groups in your community.

The Takeaway

• Advanced systemic mastocytosis is a rare and serious condition in which mast cells grow uncontrollably and cause damage to various organs.
• Treatment goals for advanced systemic mastocytosis focus on managing symptoms, preventing organ damage, and improving quality of life, with hematopoietic cell transplantation being the only potential cure.
• A Center of Excellence and a provider familiar with advanced systemic mastocytosis are important to ensure you receive the best possible treatment.