The Analysis Of Safety In Different Beginning Rescure Time Of High-dose Methotrexate Treatment For Children With Acute Lymphoblastic Leukemia

Objective: High-dose methotrexate (HD-MTX) chemotherapy play an importantrole in both shelter treatment and systemic intensive treatment for the children withacute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organswhich may cause interruption of treatment, morbidity, and mortality. The calciumfolinate (CF, also leucovorin) was adminstered by several-time injections for the rescureof HD-MTX toxicity. But it’s known that the administration of CF would weaken theanti-leukemia effect of MTX. In fact, there is no “gold-standard” about the rescuetime and doses of CF. Lately we found HD-MTX rescue in St. Jude Children’s ResearchHospital XV protocols that different from all domestic protocols. XV protocols try todecrease the rescure times and the total rescure doses in HD-MTX rescue, ensureHD-MTX effect perfectly in anti-leukemia therapy. The safety of different rescure timeof HD-MTX have been evaluated in this study in order to confirm which HD-MTXrescue regimen be more efficient and secure applied in children with acutelymphoblastic leukemia.Methods: From September2006to April2013, of27pediatric patients with acutelymphoblastic leukemia who treated in Dalian Children Hospital, the age of diagnosis2.9year-old to16year-old,86HD-MTX (5g/m2) courses were evaluated. All of theHD-MTX therapy had a pre-hydration and alkalinization from1day before thechemotherapy, and did continue hydration and alkalinization from the therapy beginningto the MTX plasma concentration≤0.1μmol/L. The whole dose of the MTX wasadministrated by intravenous infusion in24hours. And then did to monitor MTXplasma concentration. The Team A would rescured by CF which began at36hour, total56cases; and the Team B would rescured at42hour, total30cases. Rescure each6 hours from beginning, and stopped when the MTX plasma concentration≤0.1μmol/L.To observe the○1MTX plasma concentrations at23hour,42hour, and66hour;○2times dose of CF administration;○3whole dose of CF; and○4the adverse andtoxicity effects occurred at day1to day7after therapy, which included the bonemarrow suppression, liver function abnormal, gastrointestinal symptoms, the mucosaldamage of the mouth and the anus, the erythra and the subsquent infection aftermyelo-suppression, all of the effects had been indexed to grade Ⅰ to Ⅳ by the tableof common terminology criteria for adverse events of anti-cancer drugs by the PekingUnion Medical College Hospital. The data analysis was completed by SPSS13.0.Result:1. There is no difference in statistical in the MTX plasma concentration at42hour(P=0.186) and66hour (P=0.278) for the2teams.2. There is no statistical difference in the extra CF rescure times, and in the ratioof the total CF dosage and the total MTX dosage.3. The most toxicity and adverse effects in this study were the myelo-suppression(83.72%), liver function abnormal (48.84%), gastrointestinal symptoms (20.93%) andthe mucosal damage of the mouth and the anus (17.44).4. There is no statistical difference (P>0.05) in the toxicity and adverse effectsbetween the both teams, which included bone marrow suppression (P=0.062), mucosaldamage of the mouth and the anus (P=0.372), gastrointestinal symptoms (P=0.442),liver function abnormal (P=0.386), the erythra (P=0.540) and the subsquent infectionafter bone myelo-suppression (P=0.236).Conclusion:1. For children with acute lymphoblastic leukemia, in HD-MTX therapy, CFrescue from42hour has the same safety as that of from36hour.2. Rescure from42hour can decrease the times of using CF.3. Due to safety of delayed rescue, CF rescue from42hour could replacement ofthat from36hour clinically.