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Updated: Aug 26, 2026
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Correlation of cerebrospinal fluid beta-glucuronidase activity with plasma methotrexate concentrations in leukemic
Vasiliki Vlacha1, Maria Eliopoulou, Stavros Haidas
1Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Patras, School of Medicine, General University Hospital, Patras, Greece. vasovlaka@mail.gr
Background:
The activity of lysosomal enzymes is increased in body fluids during inflammation, in which cellular malfunction and cellular death occurs. Because chemotherapy also causes cell malfunction and death, for identifying a neurologic effect, we studied the activity of beta-glucuronidase in the cerebrospinal fluid (CSF) of leukemic children during treatment.
Procedure:
The beta-glucuronidase activity in CSF was determined in 13 patients with B-precursor acute lymphoblastic leukemia (ALL) treated with the medium risk arm of ALL Berlin-Frankfurt-Munster (BFM) 95 protocol. Plasma methotrexate (MTX) levels were determined at 24 and 48 hr after the infusion of high-dose (5 g/m(2)/24 hr) MTX (MCA phase).
Results:
The mean (SD) beta-glucuronidase activity prior to the onset of chemotherapy was 19.9 (5.6) nmoles/4-methylumbelliferone/ml/hr. No significant changes in activity were noted during the phases of the protocol except of the MCA3. The activity was 24.4 (6.8) on MCA2, 28.4 (9.3) on MCA3, and 24.1 (9.5) on MCA4. The beta-glucuronidase activity was positively correlated with the plasma MTX levels at both 24 hr (r = 0.483, P = 0.006) and 48 hr (r = 0.676, P < 0.0001). No progressive changes were noted during the different phases of the protocol. The greatest beta-glucuronidase activity was measured in two patients with neurotoxicity.
Conclusions:
The beta-glucuronidase activity is increased in the CSF of leukemic children receiving high-dose MTX and particularly in neurotoxicity. It is positively correlated with plasma MTX levels. No cumulative effect of the chemotherapy was observed. The increased beta-glucuronidase activity is most likely due to enzyme leakage through the cell membranes caused mainly by a toxic effect of MTX on the cells of the central nervous system (CNS).
