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High glucocorticoid receptor content of leukemic blasts is a favorable
prognostic factor in childhood acute lymphoblastic leukemia
GJ Kato, FF Quddus, JJ Shuster, J Boyett, JD Pullen, MJ Borowitz, VM Whitehead, WM Crist and BG Leventhal
Department of Pediatrics, Johns Hopkins University School of Medicine,
Baltimore, MD.
We have previously shown that the number of glucocorticoid receptors (GR)
per cell in malignant lymphoblasts from children with newly diagnosed
pre-B- and early pre-B-cell acute lymphoblastic leukemia (ALL) has a
positive correlation with the probability of successful remission induction
(Quddus et al, Cancer Res, 45:6482, 1985). We report now on the long-term
outcome for these patients treated on a single protocol with 3 different
treatment arms, all of which included glucocorticoid pulses during
maintenance therapy. GR were quantitated in leukemic cells from 546
children with ALL at the time of diagnosis. Immunophenotyping studies were
performed on all specimens. Prior studies showed that in pre-B- and early
pre-B-cell ALL, successful remission induction was associated with a median
GR number of 9,900 sites/cell, whereas induction failure was associated
with a median receptor number of 4,800 sites/cell. Long-term follow-up of
these patients shows an association between higher GR number and improved
prognosis. The 5-year event-free survival of 61.0% (SE 2.8%) for patients
whose leukemic cells had greater than 8,000 receptors/cell and 47.3% (SE
3.3%) for those with less than 8,000 receptors/cell is significantly
different (P < .001). This difference remains significant when adjusted
multivariately for blast immunophenotype and clinical risk factors (P <
.001) or for treatment type (P < .001). We conclude that GR number
greater than 8,000 sites/leukemic cell is a favorable prognostic marker for
children with acute lymphocytic leukemia. This finding offers deeper
insights into molecular mechanisms of anti- leukemia therapy and suggests
that manipulation of steroid receptor number might augment the antitumor
response, thus opening new avenues for basic and clinical research.
Volume 82,
Issue 8,
pp. 2304-2309,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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