Growth characteristics of leukemic and normal hematopoietic cells in Ph' + chronic myelogenous leukemia and effects of intensive treatment

The proliferative and differentiation characteristics of leukemic cells from chronic phase (Ph'+) CML were examined in vitro and compared to those of hematopoietic precursors from normal individuals. The rates of proliferation and differentiation of the leukemic and normal precursors were very similar and only minor differences were discerned. Serial direct cytogenetic analyses of fresh marrow aspirations were performed on 28 patients with early Ph'+ CML prior to and during treatment with an intensive combination chemotherapy regimen (L-15 protocol), which destroyed a large fraction of the leukemic population and permitted repopulation of the marrow with predominantly Ph'-negative cells in about half of the patients. However, most of the complete remissions were of short duration. Even when no Ph'+ cells were found on direct cytogenetic preparations of fresh marrow aspirates, some Ph'+ metaphases were invariably found in cells arising from cultures of the core marrow biopsies and/or in colonies arising from concentrated marrow large cell fractions obtained by cell separation procedures. In several patients prior to treatment with the L-15 protocol, a significant percentage of Ph'-negative metaphases were found in colonies arising from blood small cell fractions, while the direct marrow cytogenetic analysis showed only Ph'+ metaphases. It is concluded that only subtle differences exist between the normal and leukemic cells, and it is doubtful if it will be possible to selectively eradicate the leukemic population with currently available chemotherapeutic agents without encountering fatalities due to destruction of residual normal stem cells.