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Quantitation of Minimal Residual Disease in Acute Myeloid Leukemia by Tryptase Monitoring Identifies a Group of Patients with a High Risk of Relapse

Authors' Affiliations: ¹ Department of Internal Medicine I, Division of Hematology and Hemostaseology; ² Department of Internal Medicine I, Center of Excellence for Clinical and Experimental Oncology (CLEXO), Division of Bone Marrow Transplantation; ³ Clinical Institute of Medical and Chemical Laboratory Diagnostics; and ⁴ Institute of Environmental Health, Medical University of Vienna, Vienna, Austria

Requests for reprints: Wolfgang R. Sperr, Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400-6085; Fax: 43-1-402-6930; E-mail: wolfgang.r.sperr{at}meduniwien.ac.at.

Purpose: Recent data suggest that tryptase is produced by blast cells in a group of patients with acute myeloid leukemia (AML). In these patients, serum tryptase levels are elevated at diagnosis and decrease to normal (<15 ng/mL) or near normal values in those achieving complete hematologic remission (CR) after chemotherapy.

Patients: In this study, we examined the value of tryptase as a marker of minimal residual AML. In 61 patients with de novo AML exhibiting elevated serum tryptase (>15 ng/mL) at diagnosis, tryptase levels were measured serially during and after chemotherapy by a fluoroenzyme immunoassay.

Results: Of the 61 patients, 42 (68.9%) entered hematologic CR in response to induction chemotherapy. Twenty-nine of these 42 patients also entered biochemical remission (BR) defined by a decrease of tryptase levels to normal (<15 ng/mL). The remaining 13 patients exhibited elevated enzyme levels despite of hematologic CR. As assessed by multivariate analysis, the elevated tryptase in CR was found to be an independent prognostic variable concerning disease-free survival. Thus, AML relapses occurred in 15 of 29 patients with CR + BR (52%) and in 12 of 13 patients with CR without BR (92%), resulting in a significantly reduced probability of continuous CR for patients with CR without BR (P < 0.05). In all patients with continuous hematologic CR, tryptase levels remained constantly normal, whereas a recurrent elevation of tryptase in CR was invariably followed by a hematologic relapse.

Conclusion: A persistently elevated tryptase level in AML in CR is indicative of minimal residual AML and associated with a high risk of relapse.