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Prognostic significance of fluorescence intensity of surface marker
expression in childhood B-precursor acute lymphoblastic leukemia. A
Pediatric Oncology Group Study
MJ Borowitz, J Shuster, AJ Carroll, M Nash, AT Look, B Camitta, D Mahoney, SJ Lauer and DJ Pullen
Pediatric Oncology Group, Chicago, IL 60611, USA.
This report describes the prognostic significance of the intensity of
surface membrane antigen expression in a series of 1,231 children older
than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia
(ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All
patients had dual-color flow cytometric immunophenotyping performed at a
central reference laboratory with a standard panel of monoclonal
antibodies. The flow cytometers used in the study were calibrated with a
standard fluorescence microparticle that permitted conversion of relative
fluorescence channels to standard units of mean equivalents of soluble
fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45
and CD20 was significantly associated with event-free survival (EFS),
whereas other markers showed no significant correlation with outcome.
Patients whose blasts were greater than the 75th percentile of intensity
for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of
the intensity of normal lymphocytes) fared significantly worse than those
with lower- density CD45, and those whose blasts were greater than the 25th
percentile of intensity for CD20 (corresponding to 17,900 MESF units with
CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was
independently correlated with outcome. There was no significant correlation
between intensity of expression of either antigen and traditional clinical
risk factors, ploidy, or t(9;22) or t(1;19). All patients with t(4;11) had
CD45 intensity greater than the 75th percentile, but CD45 intensity
retained its prognostic significance after adjusting for t(4;11). In
multivariate analysis, both CD45 intensity greater than the 75th percentile
and CD20 intensity greater than the 25th percentile were significantly
correlated with poor outcome independently of previously reported poor
prognostic factors including National Cancer Institute (NCI) risk group,
ploidy, trisomies of 4 and 10, and adverse translocations including
t(1;19), t(9;22), and t(4;11). We conclude that in childhood B-precursor
ALL, the intensity of expression of CD20 and CD45 provides prognostic
information not available from simple consideration of antigen expression
as positive or negative, and adds to that obtained from traditional
clinical and biologic risk factors.
Volume 89,
Issue 11,
pp. 3960-3966,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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