A new study has demonstrated the utility of establishing individualized reference ranges for baseline serum tryptase (BST) levels in the diagnosis and management of people with systemic mastocytosis (SM) and other myeloid neoplasms.

The study, published in Blood Advances, developed a model of BST levels based on the hereditary trait alpha-tryptasemia (HαT), which is caused by an elevated germline TPSAB1 copy number. The research team used this model to determine useful diagnostic clinical reference ranges for individual patients.

“Modeling BST levels based upon TPSAB1 replication number we generate new individualized clinical reference values for the upper limit of ‘normal’,” the authors explained. “Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease.”

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Using the model, the research team discovered that significant elevations in BST levels, which would typically suggest the need for a bone marrow biopsy, can also result from higher copy numbers of TPSAB1. In these cases, increased BST levels are “normal” for those patients, meaning that a bone marrow biopsy might not be necessary.

For the study, 1178 study participants from several specialized centers were recruited and had their BST levels assessed and tryptase genotyping performed. Of these, 575 participants were specifically referred for mast cell disorder evaluation or diagnosis and underwent bone marrow aspiration and biopsy.

Based on the data obtained, the authors created an online application for clinical use that redefines the upper limits of normal BST levels for patients with HαT as a function of TPSAB1 replication number.

The app can be used to determine the need for bone marrow biopsy and/or more extensive clinical evaluation of patients with elevated BST levels, regardless of symptoms or clinical presentation. Given that other factors, such as renal dysfunction, can affect BST levels, the authors recommend further prospective studies to evaluate the usefulness of the new reference values in broader patient groups.

Reference

Chovanec J, Tunc I, Hughes J, et al. Genetically determining individualized clinical reference ranges for the biomarker tryptase can limit unnecessary procedures and unmask myeloid neoplasms. Blood Adv. Published online October 1, 2022. doi:10.1182/bloodadvances.2022007936