Patients with systemic mastocytosis and an associated hematologic neoplasm (SM-AHN) experienced markedly different outcomes depending on how genetic mutations were distributed across their cells, with distinct mutation patterns linked to more favorable disease, according to a study published recently in Blood Advances.
Most patients with SM-AHN have the KIT p.D816V mutation — the most common cause of SM — alongside another mutation that causes the AHN portion of their diagnosis. The study’s authors wanted to better understand which mutations appeared in the mast cells and cancer cells of patients with SM-AHN, and how those mutations affected their prognosis.
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In this analysis of 79 patients with SM-AHN, investigators found that 27% had genetically unrelated mutations in their mast cells and the accompanying blood cancer cells — meaning the mutations causing SM and the AHN likely occurred separately. These patients more often showed symptoms tied to mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults., such as anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis., osteoporosis and skin lesions, yet had less aggressive disease and longer progression-free survival.
In contrast, 73% of patients had shared mutations across both cell types, meaning the same mutations caused both SM and the AHN. This was correlated with more advanced illness, including low blood counts and enlarged organs in addition to shorter survival.
SM-AHN occurs in 5% to 15% of cases of SM and includes a wide range of coexisting blood cancers. In this cohort of patients, 89% had one associated neoplasm, and 11% had two. Most cases involved myeloid cancers such as chronic myelomonocytic leukemia (27%), acute myeloid leukemia (21%) or myelodysplastic syndromes (15%), while lymphoid cancers were less common at 10%. Disease subtypes ranged from indolent to aggressive forms, with 43% classified as aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases..
Read more about the prognosis of SM
The KIT p.D816V mutation was found in most patients. It appeared only in mast cells in 38% of cases but was shared between mast cells and cancer cells in 62%. Additional cancer-related mutations were present in 86% of patients, often overlapping across cell types. Based on how and when these mutations appeared, researchers identified four biological subgroups, reflecting different paths of disease development.
“Globally, our findings suggest the existence of distinct underlying biological scenarios in SM-AHN,” the authors said.
These genetic patterns translated into meaningful clinical differences. Patients with unrelated mutations had lower levels of disease markers, fewer affected cells and reduced rates of progression. Their estimated five-year progression-free survival was 85% compared with 69% in those with shared mutations. Factors such as anemia, organ enlargement and multiple mutations further worsened outcomes.
For patients, these findings suggest that detailed genetic testing of bone marrow can clarify how aggressive the disease may be. Those with separate mutation patterns may expect a slower course and fewer complications, while patients with shared mutations may need closer monitoring and potentially earlier or more intensive treatment.
