Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome andcan be used to optimize therapy
Ac. Rawstron et al., Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome andcan be used to optimize therapy, BLOOD, 98(1), 2001, pp. 29-35
Previous studies have suggested that the level of residual disease at the e
nd of therapy predicts outcome in chronic lymphocytic leukemia (CLL). Howev
er, available methods for detecting CLL cells are either insensitive or not
routinely applicable. A flow cytometric assay was developed that can diffe
rentiate 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 10(4)
to 10(5) leukocytes in all patients. We have compared this assay to convent
ional assessment in 104 patients treated with CAMPATH-1H and/or autologous
transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly d
epleted in responding patients, but remained detectable in nonresponders. P
atients with more than 0.01 x 10(9)/L circulating CLL cells always had sign
ificant (> 5%) marrow disease, and blood monitoring could be used to time m
arrow assessments. In 25 out of 104 patients achieving complete remission b
y National Cancer Institute (NCI) criteria, the detection of residual bone
marrow disease at more than 0.05% of leukocytes in 6 but of 25 patients pre
dicted 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% CL
L cells at end of treatment. All patients with detectable disease have prog
ressively increasing disease levels on follow-up. The use of sensitive tech
niques, such as the flow assay described here, allow accurate quantitation
of disease levels and provide an accurate method for guiding therapy and pr
edicting outcome. These results suggest that the eradication of detectable
disease may lead to improved survival and should be tested in future studie
s. (C) 2001 by The American Society of Hematology.