Neoplasma Vol.53, p.168-173, 2006
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| Title: Resistance to glucocorticoids in childhood acute lymphoblastic
leukemia:
impact of relationship between ex vivo sensitivity and in vivo
concentration on risk factor analysis
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| Author: J., STYCZYNSKI,
; A., KOLTAN
; M., WYSOCKI
; |
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Abstract: Resistance to glucocorticoids remains one of the main obstacles in
therapy of childhood acute lymphoblastic leukemia
(ALL). The aim of the study was the analysis of relationship
between ex vivo drug resistance of prednisolone and dexamethasone
and exposure to these drugs in childhood ALL, with respect to risk
factor analysis. Ex vivo resistance to both
glucocorticoids was compared to maximum drug concentration
achievable in body fluids, calculated in mathematical
model. Drug resistance to vincristine and L-asparaginase,
expression of multidrug resistance and apoptosis proteins was
also determined. Concentration of both glucocorticoids in
extracellular fluid was higher than drug resistance in the
following
groups of patients: in initial ALL patients, in patients staying
in remission during follow-up, and in prednisolone good
responders. Factors significant by multivariate analysis were
early bone marrow response by day 15 and concentration of
prednisolone higher than ex vivo prednisolone resistance. For
initial ALL patients with determined response to initial
prednisolone monotherapy, factors significant by univariate
analysis were early bone marrow response, and exposure to
glucocorticoids higher than ex vivo resistance to these drugs. No
factor was significant by multivariate analysis in this group.
Risk factor analysis showed that concentration of prednisolone and
dexamethasone higher than respective ex vivo drug resistance,
is a strongest prognostic factor in childhood ALL.
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| Keywords: acute lymphoblastic leukemia, prednisolone, dexamethasone,
glucocorticoids, drug resistance, risk factors
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| Year: 2006, Volume: 53, Issue: |
Page From: 168, Page To: 173 |
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