Direct Measurement of Leukemic Cell Turnover (Synthesis and Removal) in Patients With Chronic Lymphocytic Leukemia Using Deuterated Water (GAC 0004)
Chronic lymphocytic leukemia. B-cell chronic lymphocytic leukemia (B-CLL) is the most
prevalent leukemia in the Western Hemisphere, accounting for ~25% of all leukemia's. It
represents a monoclonal expansion of small, long-lived, apparently slowly dividing CD5+ B
cells. Because of the low proliferative index and a presumed uniform proliferative rate of
B-CLL cells in vivo (a fact not yet tested or documented), B-CLL appears to be primarily a
disease of accumulation rather than proliferation.
B-CLL remains an incurable illness and there is no survival benefit to early intervention.
Therefore, patients with early stage disease are usually followed closely without initiating
treatment. Patients with more extensive disease or progressive cytopenias are eventually
treated with cytotoxic agents, with or without prednisone, or with nucleoside analogues that
promote apoptosis in the leukemic cells. The clinical outcome of the disease is determined
both by the profound dysregulation of the immune system that results in infection and
autoimmunity and by leukemic infiltration and destruction of organs. Autoimmune phenomena
are common and frequently directed against hematopoietic cells, resulting in autoimmune
hemolytic anemia (10-25%) or immune thrombocytopenia.
Observational Model: Cohort, Time Perspective: Prospective
B Cell Chronic Lymphocytic Leukemia Subgroups: Direct measurement of leukemic cell turnover (synthesis and removal) using deuterated water as a DNA-labeling agent in patients with chronic lymphocytic leukemia
We believe that the results of these studies may identify in vivo correlates of the in vitro studies we have performed previously. Kinetic analyses may be another way to identify patients with different levels of risk from this disease and thereby provide an additional prognostic parameter. This information may also help to individualize future therapies for specific patients based on the in vivo biology in their particular B-CLL clone.
Nicholas Chiorazzi, MD
Feinstein Institute for Medical Research
United States: Institutional Review Board
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