Looking at the mix of normal and abnormal mast cells in the bone marrow could help doctors better distinguish less aggressive forms of systemic mastocytosis (SM) from advanced disease, according to a study published recently in Clinical Cytometry.
The approach may offer a fast and widely available tool for diagnosis, risk assessment and monitoring, although more research is needed to determine whether it can predict long-term outcomes.
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Researchers evaluated 207 patients with a clonal mast cell diseaseMast cell disease A group of conditions in which mast cells behave abnormally by building up in excess, releasing chemicals too easily or both. Includes mastocytosis, mast cell activation syndrome and hereditary alpha-tryptasemia., including 16 with monoclonal mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. syndrome, 165 with nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM. and 26 with advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. (AdvSMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm.).
They found that overall, 62% had both normal and abnormal mast cells, a pattern the researchers called partial aberrancy. This included 75% of patients with monoclonal mast cell activation syndrome, 67% with nonadvanced SM and 27% of those with AdvSM.
This partial aberrancy was associated with signs of less severe disease. Compared with patients whose mast cells were fully abnormal, those with partial aberrancy generally had a lower mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. burden, lower KIT D816V variant allele fractions (the percentage of cells carrying the mutation) and lower baseline serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM.. They also had blood counts that were closer to normal.
Read more about SM prognosis
In patients with AdvSM — 92% of whom had SM with an associated hematological neoplasmSM with an associated hematological neoplasm A form of advanced SM and the second-most common subtype of SM overall. In this subtype, SM occurs alongside another blood disorder. Also called SM with an associated myeloid neoplasm. (SM-AHN), meaning SM with another blood cancer — the researchers classified patients by the severity of the SM component of their diagnosis. They found that partial aberrancy occurred in 46% of patients with an indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases. component, but only in 8% of patients with an 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. component.
The researchers found that partial aberrancy, the percentage of abnormal bone marrow mast cells and KIT D816V variant allele fraction were the three most informative characteristics for distinguishing indolent from aggressive disease.
They noted that “partial aberrancy was most prevalent in indolent clonal [mast cell] disorders,” declining from 75% in monoclonal mast cell activation syndrome and 88% in bone marrow mastocytosisBone marrow mastocytosis A subtype of indolent SM that occurs when the excess mast cells accumulate in the bone marrow, but not the skin or other organs. to 56% in indolent SM and 27% in AdvSM.
For patients, these findings could make test results more informative when doctors are determining how aggressive mast cell disease may be. However, partial aberrancy should not be interpreted as a guarantee that disease will remain mild. Among patients with indolent disease, 3% with partial aberrancy and 5% with full aberrancy died, with no significant difference in transformation or overall survival.
The researchers emphasized that longer follow-up is needed to establish whether partial aberrancy reliably predicts a lower risk of progression and longer survival. They concluded that assessing normal and abnormal mast cell populations “may also be used in SM disease follow-up and treatment monitoring,” potentially giving clinicians another practical measure to track disease over time.
