Diagnostic and Prognostic Significance of Tryptase in Clinical Hematology: A Single Center Experience from 1070 Patients.

Recent data suggest that tryptase is expressed in neoplastic cells in various myeloid neoplasms. In this study, serum tryptase levels were determined by a fluoroenzyme-immunoassay in 165 healthy subjects, in 925 patients (pts) with hematologic malignancies (myeloproliferative disorders, MPD, n=150; myelodysplastic syndromes, MDS, n=233; acute myeloid leukemia, AML, n=317; acute lymphatic leukemia, ALL, n=26, Non Hodgkin′s lymphomas, NHL, n=30; systemic mastocytosis, SM, n=89), and in a large cohort of control cases (pregnant women, n=11; hepathopathy, n=7; renal failure, n=18; helminth infections, n=29; reactive leukocytosis/thrombocytosis or idiopathic cytopenia, n=115). In healthy subjects, the 95%-percentile ranged between 2.4 and 9.5 ng/ml (median 5.7 ng/ml). Healthy controls aged ≤ 16 years had a slightly lower median serum tryptase level compared to older control subjects (p=0.03). Among pts with non hematologic disorders, slightly elevated serum tryptase levels (up to 24 ng/ml) were detectable in 6/18 pts with severe renal failure and in 3/29 pts with helminth infections. When analyzing hematologic malignancies, tryptase levels >15 ng/ml could be detected in pts with myeloid neoplasms exclusively, whereas in most pts with lymphoproliferative disorders, tryptase levels were normal. Among myeloid neoplasms, elevated tryptase levels were recorded in 83% of the pts with SM, 36% of pts with AML, 34% of the pts with CML, and 29% of the pts with MDS. The highest tryptase levels, sometimes exceeding 1000 ng/ml, were found in pts with SM or AML-M4eo. In pts with CML, elevated tryptase levels were found to be associated with an unfavorable prognosis concerning survival (survival in CML pts with tryptase <15 ng/ml: 100% vs 71% in those with >15 ng/ml, after 60 months, p<0.007). In most pts with AML, SM, or CML, the initially enhanced serum tryptase levels decreased in response to successful cytoreductive or targeted therapy. In pts with AML, a persistently elevated serum tryptase in complete hematologic remission (CR) was found to be associated with an increased risk of relapse compared to those with normal tryptase in CR. In summary, tryptase is a new and simple diagnostic marker of myeloid neoplasms. In SM, AML, and CML, tryptase is also a useful marker to monitor (minimal residual) disease during treatment with cytoreductive or targeted drugs. Moreover, in AML and CML, measurement of tryptase is of prognostic significance. All in all, tryptase is recommended as a new important serum-marker in clinical hematology.