临床论著
Li Xiuhea;Du Juana;Yang Lia;Yang Pinga;Zhong Jiaqia;Zhou Kuna;Gao Wenwena;Ying Donga;Zhu Xiaofana;Zou Yaoa
2009, 11(2): 82-5.
Objective: To study the effects of highdose methotrexate on liver and renal function in children with acute lymphoblastic leukemia. Methods:From March 2004 to May 2008, 165 hospitalized children with acute lymphoblastic leukemia were enrolled in the study and divided into two groups: the 3 g/m2 dose group (119 cases) and the 5 g/m2 dose group (46 cases). The 3 g/m2 dose group comprised 64 men and 55 women with average age of（104.88±21.40）months. The 5 g/m2 dose group comprised 37 men and 9 women with average age of（101.57±20.43）months. The drug administration was as follows: A bolus dose of onesixth of a total dose of methotrexate 3 g/m2 or 5 g/m2 was infused intravenously and was completed within 30 minutes, then the rest fivesixths dose was infused intravenously and was completed within 23.5 hours, while an IV infusion of 5% sodium bicarbonate 3~5 ml/kg was given until the blood methotrexate concentration was < 0.1 μmol/L and urinary pH was 6~8. An IV fluid hydration 2~3 L/m2 daily was given. An IV calcium foliate was given 36 hours after methotrexate administration for rescue. A total calcium foliate dose was 3%~5% of methotrexate dose, and the total dose was divided into 6~8 doses, one dose every 6 hours was given, and the initial dose was double. An IV infusion of reduced glutathione 0.6~1.2 g/d and an IV infusion of polygene phosphateidylcholine 232.5~465 mg/d were given for 10~14 days, respectively. Blood methotrexate concentration was measured 24, 36, 48, 72, and 96 hours after administration. Liver and renal function was recorded before and 2~7 days after methotrexate administration, as well as after chemotherapy completion. The urinary volume and pH were recorded 24 hours after chemotherapy initiation. Results: Blood methotrexate concentrations 24, 36, and 48 hours after administration in the 5 g/m2 dose and the 3 g/m2 dose groups were（130.99±67.23）μmol/L,（1.95±0.98）μmol/L,（2.13±3.03）μmol/L, and（55.02±29.46）μmol/L,（1.22±0.75）μmol/L,（1.28±2.75）μmol/L, respectively. The differences were statistically significant（P＜0.01, P＜0.05, P＜0.05）. During chemotherapy, γ-GT, TBill, and DBill levels in the 5 g/m2 dose and the 3 g/m2 dose groups were respectively（63.94±76.41）U/L,（24.87±42.91）μmol/L,（12.19±29.92）μmol/L, and（40.72±35.34）U/L,（13.01±6.26）μmol/L,（4.39±2.59）μmol/L, the differences were statistically significant (all P<0.01). The ALT, AST and ALP levels in the 5 g/m2 dose and 3 g/m2 dose groups were respectively （187.29±171.18）U/L, （85.47±111.59）U/L,（141.71±69.24）U/L, and（165.93±178.84）U/L,（73.45±82.42）U/L,（138.60±59.92）U/L, the differences were statistically significant (all P<0.05). There were no statistical differences between during treatment and before treatment in both groups, as well as between both groups during treatment (all P>0.05). After liverprotective treatment, the ALT, AST and ALP levels decreased markedly, and the ALT, AST and ALP levels in the 5 g/m2 dose and 3 g/m2 dose groups were respectively（47.86±37.84）U/L,（24.00±10.78）U/L,（115.40±34.43）U/L and（75.16±68.52）U/L,（32.78±27.65）U/L,（151.27±60.18）U/L, and the differences were statistically significant (all P<0.05). In the first and second days, the fluid output in the 5 g/m2 dose and 3 g/m2 dose groups were respectively (3 673±974) ml,（4 216±1 189）ml and（3 236±1 039）ml,（3 832±1 134）ml, the fluid output was higher in the 5 g/m2 dose group than in the 3 g/m2 dose group, and the differences were statistically significant (P<0.05). No marked changes in urinary pH were found. Conclusion: Highdose methotrexate can cause liver damage in children with acute lymphoblastic leukemia, and the intensity of damage is doserelated. Reduced glutethine plus polygene phosphateidylcholine has protective effects to liver.
