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Screening algorithm for myeloid neoplasms in those with an elevated basal serum tryptase

Published: January 12, 2022

Hereditary-alpha tryptasemia (HαT) is the most common etiology for elevated basal serum tryptase (BST) in unselected populations. However, the utility of testing for HαT by tryptase genotyping for those with elevated BST in general clinical practice was not previously defined. Aside from HαT, BST elevation - currently defined as ≥ 11.5 ng/mL – has been associated with mastocytosis and other myeloid neoplasms, eosinophilic esophagitis (EoE), rheumatoid arthritis (RA), as well as chronic kidney disease (CKD). Importantly, prior studies showing associations between elevated BST and disorders other than mastocytosis did not include tryptase genotyping. Additionally, BST variability in those with elevated BST had not been explored.

In the article by Waters et al. published in The Journal of Allergy and Clinical Immunology: In Practice, the authors reviewed medical records of 109 subjects with BST ≥ 7.5 who had been tested for HαT or had a condition that was previously linked to elevated BST. The subjects were Tricare beneficiaries who received care in the National Capital Region market of the Military Health System. Diagnoses associated with elevated BST were recorded. All BST values for the 109 subjects and concurrent medications known to alter tryptase values were analyzed. Variability of BST values was also assessed. Laboratory data was reviewed to help determine what would be an appropriate work up for an elevated BST.  

Fifty-eight subjects had elevated BST and of those 37 (63.8%) had HαT, 12 (20.7%) had myeloid neoplasms, and 7 (12.1%) had CKD. Overall, approximately 90% percent of subjects with elevated BST had HαT, CKD, myeloid neoplasms, or a combination of these. Elevated BST was found to be independent of HαT in one subject with chronic eosinophilic leukemia, one subject with myelodysplastic syndrome, and two subjects with CKD. No subject with EoE (5 subjects) or RA (2 subjects) was found to have elevated BST in the absence of HαT. Fifty-one individuals had at least one high-normal BST value (> 7.4 and < 11.5 ng/mL). Of these, 8 (15.7%) had myeloid neoplasms and 6 (11.8%) had HαT. BST variability was found to be increased in 41.5% of subjects with elevated BST regardless of etiology and when taking medications known to alter tryptase values into account. Urinary 24-hour N-methylhistamine (N-MH) and KIT p.D816V testing of blood were shown to be independently useful as screening markers for mastocytosis and six of 25 (24%) subjects with HαT had elevated basophil histamine release.

Waters et al. propose an algorithm to screen for myeloid neoplasms for those with elevated BST. They recommend starting with tryptase genotyping, KIT p.D816V allele-specific PCR of blood, 24-hour urinary N-MH, kidney function, and complete blood count with differential. Bone marrow evaluation would then be offered to those who a) test negative for both HαT and CKD b) those with detectable KIT p.D816V or with elevated N-MH and c) those who test positive for HαT or CKD but have BST values that exceed ranges reported for the tryptase genotype or degree of kidney disease. The authors suggest obtaining serial BST measurements in those with elevated BST to establish the baseline degree of variability.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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