| Objective: In-depth exploration of the value of idarubicin(IDA)in the treatment of adult acute myeloid leukemia(AML),analyze and compare the treatment response and prognosis of IDA and daunorubicin(DNR)combined with cytarabine(Ara-C)in adult newly-treated AML patients,provide a reference for clinicians to optimize the treatment strategies of AML patients.Methods: The clinical data and laboratory test results of 668 newly-treated AML(non-M3)patients in the Department of Hematology of Changhai Hospital from January2009 to December 2018 were retrospectively analyzed.According to different induction chemotherapy regimens,patients were divided into IA(IDA+Ara-C)group(n=303 cases)and DA(DNR+Ara-C)group(n=365 cases).Medication method for group IA: IDA10-12mg/m2/d,intravenous drip,1st to 3rd day,Ara-C 100 mg/m2/d,continuous intravenous drip for 3-5h,1st to 7th day;Drug administration method of DA group: DNR45-60mg/m2/d,intravenous drip,on the 1st to 3rd day,Ara-C 100mg/m2/d,divided into 2continuous intravenous drips for 3-5h,on the 1st to 7th day.After one course of treatment,if partial remission is achieved or the proportion of original cells decreases by ≧60%,repeat the original regimen for one course.If complete remission is not achieved in the second course of treatment,the treatment is deemed to be ineffective and switch to other chemotherapy regimens.Patients with CR after one course of treatment continued to use the original plan and then consolidated for another course.After remission,the treatments were treated with high-dose Ara-C for 3 to 4 courses.During the course of treatment,patients were dynamically monitored for minimal residual disease(MRD).After chemotherapy,the bone marrow was completely remitted,and some patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT).After treatment,the two groups All completed 36 months of follow-up.218 patients(92 in the IA group and 126 in the DA group)were tested for MRD by multiparameter flow cytometry(MFC).MFC monitoring of MRD is usually based on leukemia-related immunophenotypes(leukemia-related immunophenotypes,LAIPs)for analysis.After the patient has a complete response(CR)after induction of remission,the patient’s bone marrow specimens are collected for flow cytometry data collection.For patients undergoing regular consolidation chemotherapy,monitor MRD levels every 1-3 months.When the detected MRD level is≥0.001,it is defined as MRD positive,otherwise MRD is negative.100 patients underwent hematopoietic stem cell transplantation after bone marrow CR.According to the source of the donor,it is divided into sibling homologous donors,related haploid donors and unrelated donors.Before transplantation,BUCY scheme or FBA scheme should be used for pretreatment.If the donor is sibling homologous donors,ATG(anti-human thymic lymphoid)should not be added.Cytoglobulin),ATG must be added to prevent GVHD if there is a site incompatibility.The study analyzed and compared the objective response(ORR),progression-free survival(PFS),total survival(OS),and adverse effects of two chemotherapy regimens(IA,DA)in AML patients Differences in response,etc.;to study the relationship between MRD and prognosis of the two groups of patients by detecting the MRD in the bone marrow of the two groups of patients;and analyze and compare the PFS and OS of the two groups of patients after transplantation.All data in this study were processed by SPSS22.0 software.Results:(1)After induction therapy in the IA group,the CR rate was 70.63%,the PR rate was 9.24%,and the ORR was 79.87%.After the induction therapy in the DA group,the CR rate was 56.99%,the PR rate was 13.15%,and the ORR was 70.14%.The CR and ORR of the patients in the group were higher than those in the DA group.(2)Grouped by cytogenetic risk,the CR rate among the three groups showed a downward trend according to low,medium and high risk,but the difference was not statistically significant(P>0.05).According to the comprehensive prognostic risk,the CR and ORR of the good prognosis group of the IA group were higher than those of the DA group.There was no statistically significant difference in ORR between the two groups of patients with moderate prognosis and poor prognosis(P>0.05).(3)According to the age of patients,with 60 years old as the limit,IA patients <60 years old patients 261 cases,DA group <60 years old patients 340 cases,the CR rate of patients <60 years old in the IA group was significantly higher than that in the DA group(P<0.05)There was no statistically significant comparison of ORR between IA group and DA group≥60 years old(P>0.05).(4)According to FAB classification to compare the efficacy of M1M2 subtype and M4M5 subtype,there were107 patients with M1+M2 subtype in IA group,181 patients with M4+M5 subtype,and142 patients in DA group with M1+M2 subtype,and M4 There are 207 patients with +M5subtype.After induction therapy,the CR rate and ORR of M1+M2 subtype patients in the IA group were higher than those in the DA group(P<0.05);while the M4+M5 subtype patients in the IA group had a higher CR rate than the DA group(P<0.05),the IA group Compared with the DA group,ORR was not statistically significant(P>0.05).(5)According to the number of treatment courses of patients,with the first course of treatment as the limit,stratified comparison,the CR rate after the first course of treatment in the IA group was higher than that in the DA group,and the differences were statistically significant(P<0.05).After the second course of treatment,the CR rate and ORR of the IA group and the DA group were not statistically significant(P>0.05).(6)During the induction remission treatment of the two groups of patients,toxic and side effects were mainly manifested as bone marrow suppression,cardiotoxicity,lung infection,upper respiratory tract infection,and fungal infection.There was no statistically significant difference between the two groups(P> 0.05);The incidence of subsequent central nervous system infiltration in the IA group was lower than that in the DA group(P<0.05).(7)The median OS of patients in the IA group was 26.30 months,and the median OS of patients in the DA group was 15.68 months.The difference between the two groups was statistically significant(P=0.007).The median PFS of the IA group was 19.16 months,and the median PFS of the DA group was 13.82 months.The comparison between the two groups was statistically significant(P=0.028).(8)Because the two groups of patients with CR in the first course of treatment have more disease-free survival,the data has a higher proportion of censorship,which makes it impossible to estimate the median survival time.The median OS of patients in the IA group who reached CR in the second course of treatment was25.50 months,and the median OS of patients in the DA group was 16.38 months.The difference between the two groups was statistically significant(P=0.0119);the median of patients in the IA group The PFS was 17.27 months,and the median PFS of the DA group was 10.78 months.The difference between the two groups was statistically significant(P=0.0128).(9)There were 126 patients in the DA group who achieved CR after induction of remission,and 92 patients in the IA group who achieved CR after induction of remission.After 1-2 courses of induction chemotherapy,the two groups of patients were tested for MRD after the bone marrow reached CR.The average MRD-positive cell level of the DA group after induction of remission reached CR was 1.35%(0-3.78%),and 80 cases were MRD-positive(63.49%),46 cases(36.51%)were MRD negative.The average MRD-positive cell level of patients in the IA group after induction of remission of CR was0.93%(0-3.76%),49 cases(53.26%)were MRD-positive,and 43 cases(46.74%)were MRD-negative;the two groups of patients reached the level of induction chemotherapy.After CR,the MRD was detected after 2 courses of consolidation treatment.The average MRD-positive cell level after consolidation treatment in the DA group was 0.62%(0-3.69%),59 cases(46.83%)were MRD-positive,and 67 cases(53.17)were MRD-negative.%).In the IA group,the average MRD-positive cell level after consolidation treatment was 0.31%(0-3.65%),36 cases(39.13%)were MRD-positive,and56 cases(60.87%)were MRD-negative.There were 43 confirmed bone marrow recurrences in DA test patients,and 21 confirmed bone marrow recurrences in IA test patients.(10)Regardless of gender,age and curative effect,the number of recurrences in the MRD<0.001 group was less than that in the MRD≥0.001 group,but the recurrence rate of the two groups of patients was independent of gender,age,and whether they were refractory(P>0.05).(11)There were 21 recurrences in the IA group.Among them,there were no recurrences within 6 months,10 recurrences within 7-12 months,and 11 recurrences over 12 months.The progression-free survival of patients in the IA regimen group with MRD<0.001 was 22.5 months,while the progression-free survival of patients with MRD≥0.001 was 14.0 months.The PFS of patients with MRD negative was significantly longer than those with MRD positive(P<0.001);in DA group patients There were 43 cases of recurrence,of which 2 patients had recurrence within 6 months,20 patients had recurrence within 7-12 months,and 21 patients had recurrence after 12 months.In the DA regimen group,patients with MRD<0.001 had a progression-free survival of16.5 months,while patients with MRD≥0.001 had a progression-free survival of 6.3months.The PFS of MRD-negative patients was also significantly longer than that of MRD-positive patients(P<0.001).(12)There was no significant difference in gender,age,donor type,pretreatment plan,and MRD value of patients undergoing bone marrow transplantation between the two groups(P>0.05).(13)Through multi-factor analysis using single factor analysis and Cox proportional hazard model,it was found that pre-transplantation pre-treatment plan,donor type,and gender are not factors that affect the prognosis of patients after transplantation.Only MRD is a factor that affects patients’ OS after transplantation(P=0.042).(14)After transplantation,there were 71 patients in the subgroup with MRD<1% of the two groups of patients.All patients had no death or recurrence during the follow-up period.Therefore,the median survival time of the IA group and the DA group cannot be estimated.Compare survival curves between groups.In the subgroup with MRD≥1%,the median OS of patients in the IA group was 13 months,and the median OS of patients in the DA group was 11 months.The difference between the two groups was statistically significant(P=0.043).The median PFS of patients in the IA group was 10 months,and the median PFS of patients in the DA group was 8 months.The two groups were statistically significant(P=0.012).Conclusion:(1)Compared with the DA regimen,the IA regimen induction treatment of adult initial AML has a higher remission rate and does not increase the treatment-related toxic and side effects.(2)The IA program can prolong the OS and PFS of AML patients and reduce the subsequent infiltration of leukemia cells in the central nervous system.(3)The MRD level after treatment is highly correlated with the patient’s bone marrow recurrence.For patients undergoing allo-HSCT,in order to obtain a better treatment effect for the patient,try to make the patient’s MRD <0.01 before pretreatment.(4)The benefit of AML patients who are treated with the IA regimen will continue to the OS and PFS after allo-HSCT. |
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