Vlacha Vasiliki, Eliopoulou Maria, Haidas Stavros, Beratis Nicholas G
Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Patras, School of Medicine, General University Hospital, Patras, Greece.
Pediatr Blood Cancer. 2004 Apr;42(4):350-6. doi: 10.1002/pbc.20002.
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.
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).
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.
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).
在炎症过程中，体液中的溶酶体酶活性会升高，炎症时会发生细胞功能障碍和细胞死亡。由于化疗也会导致细胞功能障碍和死亡，为了确定化疗对神经系统的影响，我们研究了白血病儿童治疗期间脑脊液（CSF）中β-葡萄糖醛酸酶的活性。
对13例接受ALL柏林-法兰克福-明斯特（BFM）95方案中危组治疗的B前体急性淋巴细胞白血病（ALL）患者的脑脊液β-葡萄糖醛酸酶活性进行了测定。在输注高剂量（5g/m²/24小时）甲氨蝶呤（MTX）后24小时和48小时（甲氨蝶呤巩固强化期）测定血浆MTX水平。
化疗开始前β-葡萄糖醛酸酶活性的平均值（标准差）为19.9（5.6）纳摩尔/4-甲基伞形酮/毫升/小时。除甲氨蝶呤巩固强化期3外，方案各阶段的活性均无显著变化。甲氨蝶呤巩固强化期2时活性为24.4（6.8），甲氨蝶呤巩固强化期3时为28.4（9.3），甲氨蝶呤巩固强化期4时为24.1（9.5）。β-葡萄糖醛酸酶活性在24小时（r = 0.483，P = 0.006）和48小时（r = 0.
