Adverse Reactions Of High-dose Cytarabine Consolidation Therapy In Patients With Acute Myeloid Leukemia(NON-M3)

Background Acute myeloid leukemia(AML)is the most common type of acute leukemia in adults,and its annual incidence in China is about 1.62/100,000.It is essentially a heterogeneous disease caused by the malignant proliferation of hematopoietic stem cells.According to the age of the newly diagnosed AML patients,PS score and other factors to develop different induction chemotherapy regimens(such as DA regimen,IDA regimen,etc.)and treatment,AML patients can achieve complete remission(CR)ratio of 3/5-4/5.However,patients with AML who have CR have a higher recurrence rate.According to statistics,AML patients who relapse within 3 years are approximately 50-70%.For younger patients,about 60% die from disease recurrence,while older patients have a lower long-term survival rate.Therefore,the follow-up treatment of patients with CR is an important stage for many scholars to delay the survival period,and it is also a serious challenge for the treatment of AML.At present,the main treatments for patients with AML after induction of CR include consolidation chemotherapy,autologous or allogeneic hematopoietic stem cell transplantation.Although the hematopoietic stem cell transplantation technology is mature and its effect is recognized,the consolidation of chemotherapy is still the most important choice due to various factors such as economy and donor bone marrow source.According to the NCCN guidelines,Chinese guidelines,etc.,high-dose cytarabine(High Dose Ara-C,HDAra-C)consolidation chemotherapy is one of the important programs to consolidate AML.However,cytarabine has many adverse reactions,such as hematological toxicity,gastrointestinal side effects,fever,liver and kidney damage,rash,skin ulcers,etc.,especially when HDAra-c is applied,it causes severe hematological toxicity,ie,myelosuppression,manifested as anemia,neutropenia,thrombocytopenia,etc.,causing a series of adverse events.At present,there is no clear regulation for HDAra-C(3g/m2,once every 12 hours,6 doses).The two commonly used two programs in clinical practice are: 1.HDAra-C is used continuously for 3 days;HDAra-C is applied on days 1,3,and 5.However,there are still no reports on the pros and cons of the two programs,so there are still many problems to further solve the treatment plan.Objective This study retrospectively analyzed the adverse reactions of 84 AML(non-M3)patients who received different doses of cytarabine consolidation chemotherapy after CR in Tai’an Central Hospital,in order to find out the best time plan for high-dose cytarabine consolidation therapy,so as to provide reference for clinical treatment.Method A total of 84 patients with AML(non-M3)who received high-dose cytarabine consolidation therapy in Hematology Department of Tai’an Central Hospital from January 2015 to December 2018 were collected.Their age,sex,bone marrow cells at first diagnosis,chromosomes,fusion genes,blood routine after chemotherapy,liver and kidney function,body temperature sheet and blood transfusion record sheet were collected.According to the time of HDAra-C administration,the patients were divided into group I(ie Ara-C 3g/m2,each Once every 12 hours,used in the first,second,and third days,a total of 45 cases)and group II(ie,Ara-C 3g/m2,once every 12 hours,applied in the first,third,and fifth days,a total of 39 cases).Research Content Adverse reactions to cytarabine in groups I and II,ie hematological toxicity(including neutropenia,thrombocytopenia,etc.),non-hematologic toxicity(including liver damage,myocardial damage,renal dysfunction,fever,Clinical data such as sepsis and blood product infusion were analyzed by SPSS19.0 statistical software.The adverse reactions of the two groups were compared.Result 1.Hematological toxicity 1.1 Compared with group II(10.33 VS 12.23,P = 0.000;6.89 VS 6.18,P = 0.273),the occurrence time of granulocyte deficiency in group I was significantly earlier than that in group II,but there was no statistical difference in the duration of granulocyte deficiency between the two groups.1.2 The time and duration of platelet less than 20*109/L in group I were not significantly different from those in group II(11.16 VS 11.10,p=0.952,4.67 VS 4.56,p=0.863).2.Non-hematological toxicity 2.1 The incidence of liver injury events in group I was significantly lower than that in group II(χ2 = 3.959,P = 0.047,P < 0.05).2.2 The duration and total fever time of granulocyte deficiency in group I were compared with those in group II(p = 0.439,P = 0.805,P > 0.05).There was no statistical difference between group I and group II(χ2 = 1.704,p= 0.192,P > 0.05),and there was no statistical difference between group I and group II(χ2 = 1.704,P = 0.192,P > 0.05).2.3 The incidence of myocardial injury events in group I was not significantly different from that in group II(χ2 = 0.378,P = 0.539,P > 0.05).2.4 Neither group I nor group II had renal impairment.3.Blood product transfusion 3.1 There was no significant difference in mean red blood cell transfusion between group I and group II(1.85 VS 2.33,p=0.403).3.2 The average platelet transfusion volume in group I was significantly less than that in group II(1.67 VS 2.23,p=0.035),with statistical difference.Conclusion 1.Continuous application of HDAra-C for 3 days resulted in a time of granulocytosis significantly earlier than the first,third,and fifth days of application,and the amount of platelet transfusion was significantly less than that of the first,third,and fifth days.2.The incidence of liver function damage caused by continuous application of HDAra-C for 3 days was significantly lower than that of the first,third and fifth days.3.There is no significant difference between the two regimens in terms of duration of granulocytosis,time and duration of platelet lower than 20*109/L,fever,sepsis,myocardial damage,renal dysfunction and red blood cell transfusion.4.There were no deaths in group I and group II.5.The results of the above studies showed that the continuous application of the 3-day HDAra-C consolidation chemotherapy regimen had fewer adverse effects than the first,third,and fifth-day regimens,so we recommended the HDAra-C consolidation chemotherapy regimen on days 1,2,and 3.