Investigate Effects Of High-dose Methotrexate Treatment On Intestinal Mucosal Barrier In Children With Acute Lymphocytic Leukemia

Objective:To investigate the effects of high-dose methotrexate(HDMTX) treatment on intestinal mucosal barrier in children with acute lymphocytic leukemia(ALL), and the relationship between the plasma concentration of methotrexate and intestinal mucosal barrier dysfunction.Methods:The blood samples were collected from30children with ALL after1h,24h,44h and68h of intravenous drip(IV drip) HDMTX. At the same time, the blood samples were collected from30normal children. In isolated plasma, the levels of diamine oxidase(DAO) and endotoxin were measured with spectrophotometrie. and the plasma concentration of methotrexate were determined with fluorescence polarization immunoassay.Results:The level of plasma endotoxin and DAO after1h,24h,44h,68h of IV drip HDMTX were respectively higher in ALL group than in normal control group, the difference was statistically significant(P<0.01). The level of plasma endotoxin and DAO were both higher after24h and44h of IV drip HDMTX than after1h and68h of IV drip HDMTX, and reach the peak at24h. the difference was statistically significant(P<0.01). There was no significant difference between the measured results of plasma endotoxin and DAO after1h and68h of IV drip HDMTX(P>0.05). During the different courses of HDMTX treament in same patients, there was no significant difference about the levels of endotoxin and DAO between the different courses(P>0.05). The plasma concentration of methotrexate monitored was no significantly related to the level of plasma endotoxin and DAO after1h,24h,44h.68h of IV drip HDMTX(P>0.05). There were no significant difference between the male group and female group,3g/m2group and5g/m2group,3～7years old group and7-12years old group (P>0.05).Conclusions:HDMTX treatment has great effects on intestinal mucosal barrier in children with ALL, the damage is the most serious after24h of IV drip HDMTX. In the end of chemotherapy, the damage can be recovered to level of beginning chemotherapy. During the different courses of HDMTX in same patients, the intestinal mucosa barrier damage change rules are similar. Compared to the normal control group, there was obvious damage in the ALL group, which maybe correlate to the disease itself or the long-term chemotherapy. It still needs further research and understands whether there has been intestinal mucosa barrier injury before HDMTX treatment in ALL children and whether there is a cumulative increased damage in intestinal mucosa barrier.