Efficacy And Safety Of Decitabine Containing Pretreatment Regimen In Allogeneic Hematopoietic Stem Cell Transplantation For Acute Myeloid Leukemia

Objective To evaluate the clinical efficacy and safety of decitabine(DAC)combined with conventional busulfan(BU)and cyclophosphamide(CY)pretreatment regimen in allogeneic hematopoietic stem cell transplantation(Allo-HSCT)in the treatment of acute myeloid leukemia(AML)and acute myeloid leukemia with MDS transformation(MDS-AML).Methods The clinical data of 96 AML patients treated with Allo-HSCT with or without decitabine from November 10,2014 to December 23,2020 were collected retrospectively.They were divided into two groups.25 patients were treated with decitabine combined with conventional busulfan and cyclophosphamide(DAC+BUCY);71 patients were treated with routine busulfan and cyclophosphamide(BUCY).The hematopoietic reconstitution,the cumulative incidence rate of viral infection within 100 days,the cumulative incidence rate of bacterial/fungal infection within 30 days,the incidence of GVHD and the related factors affecting the prognosis were evaluated.Result The patients in DAC+BUCY group and conventional BUCY group received neutrophil count(ANC)implantation in 23 cases(92.0%)and 67 cases(95.7%)respectively.The median granulocyte reconstruction time was 12.0(9-18)days and 12.0(9-18)days respectively;The patients in DAC+BUCY group and conventional BUCY group received platelet(PLT)implantation in 14 cases(56.0%)and 33 cases(79.1%)respectively.The median megakaryocyte reconstruction time was 14(10-21)days and 13(9-30)days respectively.There was no significant statistical difference in the reconstruction time of granulocyte/megakaryocyte between the two groups(P=0.598,P=056,table 2),and there was no significant statistical difference between the two groups(P=0.649,P=0.110,table 2).2.Virus infection occurred in 13 cases(52.0%)and 23 cases(32.4%)within 100 days after transplantation in DAC+BUCY group and conventional BUCY group respectively;The cumulative incidence rate of viral infection within 100 days after transplantation in DAC+BUCY group and conventional BUCY group were(56.0±9.9)%and(25.2±5.7)%respectively.There was no significant difference in the cumulative incidence rate of viral infection after transplantation between the two groups(p=0.129,figure 3).Bacterial/fungal infection occurred in 20 cases(80%)and 38 cases(53.5%)within 30 days after transplantation in DAC+BUCY group and conventional BUCY group respectively;The cumulative incidence rate of bacterial/fungal infection within 30 days after transplantation in DAC+BUCY group and conventional BUCY group were(54.9±5.9)%and(60.0±9.8)%respectively.There was no significant difference in the cumulative incidence rate of bacterial/fungal infection after transplantation between the two groups(p=0.464,figure 4).3.The cumulative incidence of aGVHD in DAC+BUCY group and conventional BUCY group within 100 days after transplantation were(44.0±9.9)%and(31.0±5.5)%respectively.There was no significant difference between the two groups(P=0.243,Fig.1).The cumulative incidence of cGVHD within 1 year after transplantation in DAC+BUCY group and conventional BUCY group were(24.0±8.5)%and(22.5±5.0)%,respectively.There was no significant difference between the two groups(P=0.862,Fig.2).4.After transplantation,4 cases(16.0%)died in DAC+BUCY group and 24 cases(33.8%)in conventional BUCY group.The 2-year OS were(83.8±7.4)%and(70.6±6.3)%respectively.There was no significant difference in overall survival(OS)between the two groups(P=0.136,FIG.5).After transplantation,DAC+BUCY group and conventional BUCY group recurred in 2 cases(8.0%)and 24 cases(34.3%)respectively.The two-year disease-free survival(DFS)were(90.7±6.3)%and(60.2±7.5)%respectively.DFS between the two groups was statistically significant(P=0.031,Fig.6).5.According to statistics,fusion gene and recurrence after transplantation are the main risk factors affecting OS after transplantation(see Table 3 for details);Disease status before transplantation and pretreatment methods are the main risk factors affecting DFS after transplantation(see Table 4 for details).Multivariate Cox regression survival analysis found that fusion gene and recurrence after transplantation were independent prognostic factors affecting patients’ OS(see Table 5 for details).Pretreatment method,disease status before transplantation and methylation gene classification are independent prognostic factors affecting DFS(see Table 6 for details).Conclusion the effect of DAC combined with conventional BUCY before transplantation is better than that of conventional BUCY group.It does not affect the implantation rate of granulocyte/megakaryocyte,nor increase the related infection rate after transplantation and the cumulative incidence of aGVHD and cGVHD after transplantation.This study suggests that the addition of decitabine before pretreatment is an independent prognostic factor affecting DFS.DFS in DAC+BUCY group is significantly better than that in BUCY group,which significantly reduces the risk of recurrence after transplantation.