Chronic myelogenous leukemia. Prolonged survival with spontaneous decline in the frequency of Ph1-positive cells and subsequent development of mixed Ph1-positive and Ph1-negative blast crisis.

A 23-year-old man developed Ph1-positive chronic myelogenous leukemia in 1966. After two short courses of busulfan not associated with severe myelosuppression, the frequency of Ph1-positive metaphases in his bone marrow was 40%. Over the next eight years, he remained hematologically stable without further therapy. During that time there was a progressive decline in the frequency of Ph1-positive metaphases in his bone marrow to 3% by 1976. His disease subsequently transformed to an acute lymphoblastic leukemia. Cytogenetic studies of the marrow at the onset of blast crisis and of cultured marrow blast cells suggested that the blasts were a mixture of Ph1-positive and Ph1-negative cells. This patient was thus unique in that he demonstrated spontaneous decline in the frequency of Ph1-positive cells in his bone marrow and he developed blast crisis with an apparent mixture of Ph1-positive and Ph1-negative blasts. These findings demonstrate that a Ph1-positive cell clone may lose its proliferative advantage over Ph1-negative cells and raise the possibility that Ph1-negative cells persisting in patients with Ph1-positive chronic myelogenous leukemia may be abnormal and, like the Ph1-positive cells, may be susceptible to acute leukemic transformation.