| Objective: Acute lymphoblastic leukemia(ALL) is the most common malignant disease in childhood and the treatment for ALL has made great progress over the past 40 years. Advanced combine chemotherapy protocols has already increased eventfree survival up to 86%, but there are still some patients got relapse due to minimal residual diseases(MRD). Now people are aiming at improving protocols, decreasing MRD, and prolonging EFS. In many chemotherapy drugs for children ALL, LAsparaginase(L-ASP) play a key role in induction and much more, Continue the complete remission of the disease. It is well known that L-Asp is essential in chemotherapy of children with ALL. There are also some important drugs during the treatment, include glucocorticoids and anthracyclines, which may cause serious sideeffects such as osteonecrosis, vital organ-- especially heart function damage. They are clinically dose-limited in case serious complications affect the life quality or lead to death.Recently, people try to increase the dose of L-ASP in chemotherapy. In many protocols before, L-Asp only be used in the beginning induction and reinduction one time per year, such as Xinhua hospital XH-99 protocol; but in St.Jude children’s research hospital XV protocol, after induction and consolidation, L-Asp is continued for almost 5 months with 5-7 times doses than that of XH-99. in our study, two groups of patients with ALL in our hospital from 2003-2014 who accepted these two different protocols(40 in XH-99, 37 in XV) was observed. By comparing the change of MRD each year after CR and common side-effects of L-asp, we try to confirm that high-dose L-Asp is necessary and safe in the treatment of children with ALL.Methods: Methods By historical-control method, 77 children with ALL(male 43,female 34, age from 1.9 years old to 14 years old, average age(7.5 ± 2.9) were observed between 2003 and 2014 treated in children’s Hospital of Dalian.The standard of diagnosis, classification and the dan-gerous degree classification refers to "Children with acute lymphocytic leukemia diagnosis and treatment recommendations". 40 patients who received conventional dose ofL-asp were divided into three groups: low-risk group standard risk group and high-risk group, receiving each total dose of L-asp with 60000U/m2, 72000U/m2, 84000U/m2,menwhile the high dose groups receiving each total dose of L-Asp with 300000U/m2, 565000U/m2, 565000U/m2. The L-asp given in high-dose group were 5-7 times to theconventional dose group. All patients MRD were monitored by flow cytometry, MRD <0.01% was regard as negative. Meanwhile some common adverse reactions such as fast blood sugar, liver function, blood serum amylase, urine amylase and special adverse reactions also are compared by different doses of L-Asp treatment. Clinically, another common side-effect cause by L-Asp is the abnormal of clotting, fresh frozen plasma infusion is needed when serum fibrinogen < 0.8g/L(XH-99) or 0.5g/L(XV). Here the times of transfusion go into our statistics.Results:1. The observation of MRD in patients with ALL who accepted different doses of L-Asp(1) Two-group patients appeared significant difference in MRD positive rate. Children with high-dose L-Asp therapy in early have much more MRD negative ratio in the first.the second and the third years after CR.(2) For the patients who have the positive MRD after initial induction, High-dose L-Asp can decrease MRD to negative, and it is statistically significant to that of regulardose L-Asp.2. The Observation of side effects of children with ALL in different doses of LAsp Comparing to conventional dosage, patients who accepted high-dose L-Asp have no significant difference in clinic common side-effect such as hyperglycemia, pancreatitis and thrombosis; But plasma transfusion frequency is statistically significant more than that of conventional dosage. Besides, statistically significant are found that receiving high-dose L-Asp cause severely impaired of liver function than children who in conventional dosage.Conclusion:1. High-dose L-Asp can decrease MRD positive ratio in 3 years after chemotherapy beginning, that would prevent relapsing of ALL in early and mid-time of disease course.2. High-dose L-Asp can negative patients’ positive MRD after the initial induction, means the very importance of using high-dose L-Asp in early time of chemotherapy.3. Comparison of clinical common adverse reactions occurring in two groups patients with different doses of L-Asp, except liver damage and abnormal of clotting, shows no statistically significant difference, suggesting the security of using high-dose L-Asp in the treatment of children with ALL. But it is necessary to protect live function and monitor coagulation of the patients.4. Our observation shows that MRD should be monitored regularly that would be benefit to find the recurrence of positive MRD in patients during chemotherapy, especially in the later time of treatment. 1 time every 3 month would be needed. If MRD keep positive, clinical intervention should be given to improve the EFS of diseases. |
PDF Full Text Request