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Blood, 1 July 2001, Vol. 98, No. 1, pp. 29-35
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Quantitation of minimal disease levels in chronic lymphocytic
leukemia using a sensitive flow cytometric assay improves the
prediction of outcome and can be used to optimize therapy
Andy C. Rawstron,
Ben Kennedy,
Paul A. S. Evans,
Faith E. Davies,
Stephen J. Richards,
Andy P. Haynes,
Nigel H. Russell,
Geoff Hale,
Gareth J. Morgan,
Andrew S. Jack, and
Peter Hillmen
From Haematological Malignancy Diagnostic
Service, Leeds General Infirmary, Leeds, United Kingdom;
Nottingham City Hospital, Nottingham, United Kingdom; and the
Sir William Dunn School of Pathology, University of Oxford,
Oxford, United Kingdom.
Previous studies have suggested that the level of residual disease
at the end of therapy predicts outcome in chronic lymphocytic leukemia
(CLL). However, available methods for detecting CLL cells are either
insensitive or not routinely applicable. A flow cytometric assay was
developed that can differentiate CLL cells from normal B cells on the
basis of their CD19/CD5/CD20/CD79b expression. The assay is rapid and
can detect one CLL cell in 104 to 105
leukocytes in all patients. We have compared this assay to conventional assessment in 104 patients treated with CAMPATH-1H and/or autologous transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly depleted in responding patients, but remained detectable in
nonresponders. Patients with more than 0.01 × 109/L
circulating CLL cells always had significant (> 5%) marrow disease,
and blood monitoring could be used to time marrow assessments. In 25 out of 104 patients achieving complete remission by National Cancer
Institute (NCI) criteria, the detection of residual bone marrow disease
at more than 0.05% of leukocytes in 6 out of 25 patients predicted
significantly poorer event-free (P = .0001) and overall
survival (P = .007). CLL cells are detectable at a median
of 15.8 months (range, 5.5-41.8) posttreatment in 9 out of 18 evaluable
patients with less than 0.05% CLL cells at end of treatment. All
patients with detectable disease have progressively increasing disease
levels on follow-up. The use of sensitive techniques, such as the flow
assay described here, allow accurate quantitation of disease levels and
provide an accurate method for guiding therapy and predicting outcome.
These results suggest that the eradication of detectable disease may
lead to improved survival and should be tested in future studies.

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Different clinical value of minimal residual disease after autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia
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Blood 2002 99: 1873-1874.
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