Phenotypic Changes in a Case of Blast Crisis of CML: Characterization by TdT, Cytochemistry, and Cytogenetics

Abstract

Phenotypic changes in blast crisis of a case of Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia [CML] were characterized by serial terminal transferase (TdT) determinations simultaneously related to cytochemical and cytogenetic data. At the onset of the blast crisis, 90% of the blast cells were acid phosphatase-positive (focal pattern), Ph1-positive, lymphoid cells. The TdT activity amounted to 29 units/108 mononuclear cells in the peripheral blood and to 57 units/108 mononuclear cells in the bone marrow. Therapy with vincristine and prednisone caused the elimination of the TdT-positive cell population. Four months later, there was an increase in TdT-negative, myeloid blasts which was brought under control with busulfan. Cytogenetic analysis of the myeloid blasts which was brought under control with busulfan. Cytogenetic analysis of the myeloid blasts still revealed Ph1 positivity in 100% of the metaphases examined and the lack of additional chromosomal abnormalities. A 2nd relapse was dominated by TdT-containing cells with the 46,XX,Ph1 karyotype. The patient failed to achieve remission with vincristine and prednisone. Even though the TdT activity was markedly decreased, the lymphoid blast count remained elevated and the cells resisted further therapy. This failure of morphology, cytochemistry as well as cytogenetics to distinguish between the individual phenotypes emerging during the course of blast crisis of CML characterized the TdT as a cell marker of important diagnostic and therapeutically prognostic value.