| Objective:To evaluate the efficacy and safety of azacitidine in the maintenance treatment of acute myeloid leukemia(AML),and to analyze the related factors affecting the efficacy and prognosis of patients.Methods:Clinical data of 98 AML patients admitted to the Department of Hematology,The First Hospital of Lanzhou University from January 2019 to December 2022 were retrospectively collected.They were divided into maintenance group(n=41)and control group(n=57)according to whether they received azacitidine maintenance therapy after induction and consolidation therapy or hematopoietic stem cell transplantation.The regimen of the maintenance group was(36-75)mg/m~2×7d,subcutaneous injections,every 4 weeks as a course of treatment.The main endpoints were relapse-free survival(RFS)rate and overall survival(OS)rate,and the secondary endpoints were the occurrence of treatment-related adverse reactions,to evaluate the efficacy and safety of the regimen.Univariate and multivariate Cox regression was used to analyze the prognostic factors.Results:1.Efficacy evaluation:A total of 98 patients with newly diagnosed AML were collected in this study,including 41 patients in the maintenance group and 57 patients in the control group.The median follow-up time was 26.0(20.1-31.5)months.A total of 38 patients relapsed and 31 patients died.In the maintenance group,41 patients received a median of 5(2-13)courses of azacitidine maintenance therapy,of which 7relapsed and 5 died.The 2-year RFS of the maintenance group and control group were84.4%and 34.5%,respectively,and the 2-year OS were 85.9%and 47.4%,respectively,and the differences were statistically significant(P<0.05).Survival analysis of patients in each subgroup showed that for patients who did not receive hematopoietic stem cell transplantation,patients in adverse risk,patients with M2,and patients with MRD negative,the 2-year RFS and OS in the maintenance group were higher than those in the control group,and the differences were statistically significant(P<0.05).For patients with intermediate-risk,M5,and MRD-positive,the difference in RFS between the maintenance group and the control group was statistically significant,while the difference in OS was not statistically significant(P>0.05).The2-year RFS of prophylactic therapy and preemptive therapy in the AZA maintenance treatment group were 100%and 50.9%,and the 2-year OS were 96.2%and 55.6%,respectively,and the difference were statistically significant(P<0.05).The 2-year RFS and OS of the patients with maintenance treatment courses>5 were higher,both reaching 100%,while the 2-year RFS and OS of the patients with maintenance treatment courses≤5 were 66.6%and 67.7%,respectively,and the differences were statistically significant(P<0.05).The 2-year RFS of transplant patients and non-transplant patients were 100%and 70.6%,respectively,the difference was statistically significant(P=0.007),and the 2-year OS were 94.7%and 79.1%,respectively,the difference between OS was not statistically significant(P>0.05).2.Analysis of prognostic factors:In the maintenance group,the results of the univariate analysis showed that white blood cell count at initial diagnosis,azacitidine history at induction and consolidation therapy,and the number of maintenance treatment courses had statistically significant effects on RFS,and MRD status before maintenance therapy had statistically significant effects on OS(P<0.05).The above factors and other related factors were included in the multivariate Cox regression model.The results showed that the number of maintenance treatment courses(HR=0.561,95%CI 0.323-0.974,P=0.040)had a statistically significant effect on RFS.Compared with the proportion of bone marrow blast cells≥30%at initial diagnosis,the proportion of bone marrow blast cells<30%had a statistically significant effect on RFS(HR=13.945,95%CI 1.642-118.408,P=0.016).None of the variables had statistically significant effects on OS(P>0.05).3.Safety analysis:84.7%(83/98)of patients experienced at least one adverse event of any grade.In the maintenance group,the most common hematologic toxicities were neutropenia(75.6%),and thrombocytopenia(43.9%),while the most common non-hematologic adverse events were nausea(63.4%),vomiting(43.9%),fatigue(34.1%),and injection site reaction/erythema(31.7%),which were mainly grade 1-2.The above adverse events mainly occurred in the first two courses of maintenance therapy.With the increase in the number of courses,the adverse events were often alleviated or disappeared.Compared with the control group,the incidence of neutropenia,nausea,vomiting,and constipation in the maintenance group was higher,and the difference was statistically significant(P<0.05).The incidence of hematologic adverse events such as neutropenia,thrombocytopenia,anemia,and non-hematologic adverse reactions such as nausea,constipation,hepatotoxicity,and injection site reaction/erythema tended to increase with the increase of azacitidine dose.Conclusions:1.Azacitidine maintenance therapy can prolong the remission period and improve RFS and OS in AML patients.The benefits were more obvious in the subgroup of patients who didn’t receive hematopoietic stem cell transplantation,were at adverse risk,and were M2-type and MRD-negative.2.In the maintenance group,prophylactic therapy had better RFS and OS than preemptive therapy,and the transplant patients had better RFS than the non-transplant patients.The number of treatment courses and the proportion of bone marrow blast cells<30%at initial diagnosis were independent risk factors affecting RFS in maintenance patients.3.Azacitidine maintenance treatment was safe and well tolerated,the most common hematologic adverse events were neutropenia and thrombocytopenia,while the most common non-hematologic adverse events were nausea,vomiting,fatigue,and injection site reaction/erythema,which were often alleviated or disappeared with the increase of the number of courses. |
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