Bone marrow mast cell burden and serum tryptase level as markers of response in patients with systemic mastocytosis

Abstract

Two important response criteria in systemic mastocytosis (SM) are the elimination or reduction in percentage of bone marrow mast cells (MCs) and the reduction of serum tryptase levels. We investigated the accuracy of a single time point reduction of bone marrow MCs and serum tryptase level as response criteria in 50 patients with SM with available serial assessments. Bone marrow MC percentage varied significantly, with an average coefficient of variation (CV) of 65% (range, 6–173%) and 44% of patients having a CV higher than the average. The average CV for serum tryptase level was 19% (range, 0–96%), with 36% of patients having a CV higher than average. These wide variations in bone marrow MC burden and serum tryptase level were independent of the administration of SM-directed therapy, type of therapy or disease subtype. Furthermore, the achievement of a single time point therapy-induced bone marrow complete response (no histological evidence of malignant bone marrow MCs) did not correlate with tryptase level or symptomatic improvement. In conclusion, the value of single measurements of bone marrow MC percentage and serum tryptase level as response criteria in SM is not supported by clinical data. Incorporation of an assessment of the degree in reduction of MCs and tryptase, and assessment of response durability, would make response criteria more clinically meaningful.

Determination of Plasma Heparin Level Improves Identification of Systemic Mast Cell Activation Disease

“…sTryp was elevated above reference in 73% of the SM patients in this study (and elevated > 20 ng/ml in 53% of the SM patients) but was clearly less suited to indicate MC activation in MCAS patients (sensitivity only 10%), similar to previous findings ( Table 1 ). These findings are consistent with contemporary understanding that sTryp far dominantly reflects total body MC load and far less MC activation state [ 23 , 24 ]. The specificity, too, of sTryp can be adversely affected by elevated levels found in hematologic non-MC-lineage neoplasms and end-stage kidney disease.…”

Well-differentiated systemic mastocytosis showed excellent clinical response to imatinib in the absence of known molecular genetic abnormalities

“…Further, the degree of mast cell activation, and thereby serum tryptase levels can be dependent on time, external stimuli, etc. [ 13 ] In this case, unlike serum tryptase testing at the time of relapse, serum tryptase level was performed only at 1 time point. Another interesting finding at relapse was overt erythrophagocytosis observed in mast cells while the patient was neither anemic nor being transfused.…”

Secretory and Membrane-Associated Biomarkers of Mast Cell Activation and Proliferation

“…In addition, tryptase has a prognostic value, as a serum tryptase ≥125 μg/L is a negative prognostic factor for overall survival in patients with advanced SM according to the International Prognostic Scoring System for SM (IPSM) [ 53 ]. Finally, tryptase is considered one of the most reliable indicators of responsiveness to cytoreductive treatments, and total tryptase levels can be easily monitored in patients with advanced SM under cytoreductive therapies [ 54 , 55 ].…”