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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-06-1639.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2507-2513
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Circulating CD20 is detectable in the plasma of patients with
chronic lymphocytic leukemia and is of prognostic significance
Taghi Manshouri,
Kim-anh Do,
Xuemei Wang,
Francis J. Giles,
Susan M. O'Brien,
Helen Saffer,
Deborah Thomas,
Iman Jilani,
Hagop M. Kantarjian,
Michael J. Keating, and
Maher Albitar
From the Departments of Hematopathology, Biostatistics,
and Leukemia, The University of Texas M. D. Anderson Cancer
Center, Houston, TX.
CD20 is a 33- to 36-kDa transmembrane phosphoprotein involved in
the activation, proliferation, and differentiation of B lymphocytes. The predicted amino acid sequence of the CD20 suggests 4 transmembrane-spanning regions with both N- and C-termini located in
the cytoplasm. We demonstrate herein that significant levels of
circulating CD20 (cCD20) can be detected in the plasma of patients with
chronic lymphocytic leukemia (CLL) and that cCD20 interferes with the binding of rituximab, a humanized anti-CD20 monoclonal antibody, to CLL
cells. An enzyme-linked immunosorbent assay (ELISA) was developed to
measure circulating cCD20 levels in the plasma. We measured cCD20
levels in the plasma of 180 patients with CLL and correlated these
levels with clinical characteristics and outcome. Circulating CD20
levels correlated positively with  2-microglobulin level
(p = .006) and percentage of
CD38+ cells (p = .03) and negatively with
platelet count (p = .004) and hemoglobin
level (p = .02). Patients with advanced Rai
(III/IV) or Binet (C) stage disease had significantly higher levels of cCD20 than did patients with earlier-stage disease
(P = .01 and P = .006, respectively). There
was no correlation between cCD20 level and age, lymphocyte count, or
white blood cell count. Using a recursive classification method, we
found that patients with a cCD20 level more than 1875 nM/L had
significantly shorter survival than those with cCD20 1875 nM/L or below
(P = .01). The prognostic value of cCD20 was independent
of Rai staging or hemoglobin level. Prospective evaluation is indicated
to establish whether rituximab dosing should be adjusted according to
cCD20 levels.
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