Advanced systemic mastocytosis (AdvSM)

Mast cells are immune cells that take part in allergic reactions. They are made in the bone marrow, the soft tissue inside bones where blood is made. In systemic mastocytosis, abnormal mast cells build up in the marrow and can gather in other organs too.

Systemic mastocytosis ranges from milder forms, called indolent and smoldering, in which people generally live a normal or near-normal lifespan, to more serious ones. “Advanced” systemic mastocytosis is the name for three serious types: aggressive systemic mastocytosis, in which the mast cells damage organs; systemic mastocytosis with an associated hematologic neoplasm, in which a second blood cancer is found at the same time; and mast cell leukemia, the rarest and most serious type. The second type is the most common, making up about 6 or 7 in 10 advanced cases.

Two classification systems are in use, so reports can differ. The World Health Organization calls the second type “systemic mastocytosis with an associated hematologic neoplasm” (SM-AHN). The International Consensus Classification calls it systemic mastocytosis “with an associated myeloid neoplasm” (SM-AMN).

In more than 9 in 10 people with systemic mastocytosis, the mast cells carry a change in a gene called KIT, most often one known as KIT D816V. The KIT gene makes a switch that tells mast cells to grow. The change leaves that switch stuck on, so mast cells keep building up.

This change happens in cells during a person’s life. It is generally not inherited from a parent, and it is not an infection that can be caught from anyone.

Most people with advanced disease also have other gene changes in their blood cells, most often in genes called TET2, SRSF2, ASXL1, RUNX1 or JAK2. Some of these, such as changes in ASXL1, RUNX1, SRSF2 or NRAS, are linked to a harder course. They help doctors judge risk and plan treatment.

Mast cells release chemicals that cause allergy-type symptoms. People may have flushing, stomach pain, diarrhea, nausea, tiredness, low blood pressure and lightheadedness. Some have severe allergic reactions (anaphylaxis), and triggers such as temperature changes, insect stings, some pain medicines or stress can set off symptoms.

In advanced disease, mast cells also build up in and harm organs such as the liver, spleen and lymph nodes. This can cause fluid to collect in the belly and, in aggressive systemic mastocytosis, thinning bones that break easily. When a second blood cancer is present, it causes problems of its own, and sometimes that second cancer is acute myeloid leukemia.

Living with advanced systemic mastocytosis often means regular blood tests, marrow checks and clinic visits, along with care for allergy-type symptoms. People learn which triggers to avoid, and patient groups offer emergency-room plans and alert cards in case of a severe reaction.

Outlook varies widely by type and risk score, and mast cell leukemia is usually the hardest to treat. Survival figures are averages across groups of people, and they cannot predict how any one person will do.

Deciding about a transplant is hard. The team looks at the type, how well the disease has responded to medicine, other gene changes and the person’s overall health. In a German registry, people whose disease responded to treatment before transplant lived longer on average. If the disease returns afterward, a KIT pill may be used.

Most people with advanced systemic mastocytosis are treated with medicines and do not have a transplant. In a large European-led registry, about 1 in 9 people with advanced disease had a donor transplant. The transplants reported for this condition use blood-forming cells from a donor, not the person’s own cells.

Donors vary. In a German registry of people transplanted from 1999 to 2021, 6 in 10 of those with known donor details received cells from an unrelated volunteer, fully or partly matched. Most of the rest had a matched relative, and some had a half-matched (haploidentical) family donor.

Joining a registry cannot promise a match for any one person. But for the smaller group who need a transplant and have no matched relative, a volunteer donor can make it possible.