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Autologous Bone Marrow Transplantation - Blog Science Connections

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Transient Restoration of Partial Philadelphia<br />

Chromosome Negativity After Autografting in<br />

Chronic Myeloid Leukemia<br />

F. Brito-Babapulle, R. E. Marcus, F. Rassool, G Ai-Pu,<br />

K H. Th'ng, C. Dowding, D. McCarthy, D. Catovsky,<br />

D. A. G. Galton, and J. M. Goldman<br />

Evidence suggests that considerable numbers of Philadelphia chromosome<br />

(Ph 1 )-negative hematopoietic stem cells may be present, albeit in quiescent<br />

state, in the marrow of newly diagnosed patients with chronic myeloid leukemia<br />

(CML) (1 ). Some of these Ph 1 -negative stem cells may also be present in the<br />

circulation. Presumably, the clonal proliferation of Ph 1 -positive cells depends on<br />

their ability to suppress the growth of these Ph 1 -negative (putatively normal)<br />

stem cells. Because in certain clinical circumstances a Ph 1<br />

positive-negative<br />

mosaicism has been recognized (2) and because in other circumstances<br />

patients have been restored to partial or complete Ph 1<br />

negativity by administration<br />

of cytotoxic drugs (3,4), we thought that high-dose chemotherapy (or<br />

chemoradiotherapy) followed by autografting with blood-derived stem cells<br />

collected at diagnosis might give similar results.<br />

An additional rationale for developing this protocol was that we thought the<br />

probability of a patient entering the blastic phase of the disease might be<br />

directly proportional to the number of leukemic stem cells in the body, a<br />

number that might be little affected by administration of cytotoxic drugs or<br />

189

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