30 October 2025

New insights on the early detection of clonal mast cell diseases

PROSPECTOR, a prospective multi-center clinical trial, provides important results related to the diagnosis of clonal mast cell diseases, in particular systemic mastocytosis. This rare disease is associated with a wide range of symptoms and a high disease burden for those affected.

Due to the pathological proliferation and accumulation of mast cells in internal organs, especially the bone marrow, patients with mastocytosis suffer from itching, diarrhea, circulatory problems and often anaphylaxis, i.e. severe allergic reactions. The diagnosis ofter occurs late, as the symptoms are sometimes unspecific and a bone marrow biopsy is necessary to detect an increase in mast cells. The cause of mast cell proliferation is the KIT D816V mutation, which 95 percent of patients carry.

PROSPECTOR investigated the question of how frequently the genetic marker KIT D816V can be detected in blood samples and examined patients with anaphylaxis or symptoms of mast cell disease.

Early detection by blood test is possible - but not sufficient

KIT D816V was detected in the peripheral blood of 4 percent of the 381 study participants. If cases with later diagnosis by bone marrow biopsy were taken into account, the prevalence increased to 8 percent.

It is noteworthy that 80 percent of KIT D816V-positive patients had tryptase concentrations below 20 ng/ml, thus below the previously defined threshold for systemic mastocytosis. Tryptase is an enzyme that mast cells release. It is also considered a diagnostic factor. These results emphasize that a low tryptase level alone does not rule out mast cell disease.

Genetic factors and new screening approaches

In addition to the KIT mutation, hereditary alpha-tryptaseemia (HaT) was also investigated - a genetic variant that leads to permanently elevated tryptase levels in the blood. HaT was detected in 36 percent of the study participants, particularly in patients with cardiovascular symptoms. This leads to the recommendation that further diagnostics should be considered for patients with tryptase levels of 8 ng/ml and above.

Clinical relevance and outlook

The present study results suggest that patients with moderate to severe anaphylaxis should be tested more frequently for KIT D816V. The combination of tryptase levels, genetic analysis (HaT) and KIT D816V screening significantly improves the diagnosis for mast cell diseases. Nevertheless, the bone marrow biopsy remains essential for the final diagnosis.