A Study of the Kinetics of Lymphoid Cells in Patients With Monoclonal B-Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), Mantle Cell Lymphoma (MCL) and Healthy Volunteers.
Chronic lymphocytic leukemia (CLL) and its lymphoma variant, small lymphocytic lymphoma
(SLL) were for decades considered diseases caused by the progressive accumulation of
abnormal lymphocytes. The prevailing view being that CLL and SLL disease processes were
driven by an underlying defect in apoptosis. While resistance to apoptosis appears to be
important in the CLL and SLL disease process, recent studies suggest that cellular
proliferation is more important than previously realized.
Cells from individuals with CLL who drank deuterated water (heavy water) for 6 weeks showed
a turnover rate of 0.1 % to 1.1 % per day. In a second study involving CLL subjects who
drank heavy water, average CLL turnover rates were in a similar range but approximately
2-fold lower than average B-cell turnover rates from healthy individuals. These studies have
shown the safety and scientific value of using heavy water to study the kinetics of cell
proliferation in patients and normal volunteers.
We now propose this study to expand on findings by other investigators. This study will
address the site of proliferation for CLL/SLL cells and will include individuals with
monoclonal B-cell lymphocytosis (MBL), a possible precursor of CLL. Furthermore, we will
include patients with mantle cell lymphoma (MCL), a disease in which tumor proliferation
plays an important role.
Study participants will drink heavy water daily for a total of 4 weeks (labeling period)
with an optional 6 months follow up ( wash out period). Blood samples will be obtained
weekly during the labeling period. A bone marrow and/or lymph node biopsy will be obtained
where possible during the labeling period. Additional blood draws may be obtained during the
optional wash-out phase of the study to determine the rate at which tumor cells disappear.
The primary objective of this exploratory study is to obtain an estimate of the
proliferation rate of tumor cells in individuals with MBL, CLL/SLL, and MCL.
The secondary objectives are to compare proliferation rates between different anatomic
compartments, specifically peripheral blood, lymph node, and bone marrow and the estimation
of the attrition or disappearance rate of cells during an optional phase of the protocol.
Healthy volunteers may be included for comparison.
Time Perspective: Prospective
To estimate the cell proilferation rate of tumor cells in individuals with MBL, CLL/SLL, and MCL.
Thomas M Herndon, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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