Loss of terminal deoxynucleotidyl transferase (TDT) activity as a predictor of emergence of resistance to chemotherapy in a case of chronic myelogenous leukemia in blast crisis

Abstract

A 46-year-old female with chronic myelogenous leukemia (CML) in blast crisis was monitored for terminal deoxynucleotidyltransferase (TdT) activity of marrow and peripheral blood throughout the course of her illness. TdT was elevated at the time of diagnosis of blastic transformation, and the patient easily obtained remission after therapy with hydroxyurea, 6-mercaptopurine and prednisone. The patient enjoyed a remission of eight months duration, and at time of relapse, marrow TdT was again elevated. The patient again obtained complete remission with the same regimen, with the addition of vincristine, given weekly. This second remission was shortlived, however, and at relapse marrow TdT activity was undetectable. Subsequently, the patient failed to achieve remission, despite the use of a wide variety of chemotherapeutic agents. This case suggests that loss of TdT activity in blastic CML cells marks the emergence of cells resistant to existing chemotherapeutic agents.