| BackgroundFms-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)mutations occur in 25-30% of patients with acute myeloid leukemia(AML),which are characterized by high white blood cells,early recurrence and short survival,and are identified as high-risk AML by the NCCN(National Comprehensive Cancer Network)guidelines.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the methods to cure FLT3-ITD-positive AML,but the high risk of recurrence after transplantation has been a problem for the medical community.Donor lymphocyte infusion(DLI)is a common method to prevent recurrence of high-risk AML after allo-HSCT.Sorafenib is one of a FLT3 specific tyrosine inhibitors and can work as a targeted therapy for FLT3-ITD mutations.In recent years,it has been demonstrated that sorafenib maintenance therapy can significantly improve the prognosis of FLT3-ITD-positive AML after allo-HSCT.However,there were few data comparing maintenance sorafenib with prophylactic DLI in the effectiveness of preventing relapse for FLT3-ITD-positive AML patients after alloHSCT.ObjectiveTo analyses the impact of prophylactic DLI and sorafenib maintenance therapy on the FLT3-ITD positive AML after allo-HSCT.MethodsWe performed a retrospective study with 68 FLT3-ITD-positive AML patients who received allo-HSCT in our center from January 2014 to December 2018.According to different post-transplant treatment methods,they were divided into three groups,group A: 24 of them received maintenance sorafenib;group B: 12 of the patients received prophylactic DLI;group C: the rest of 32 patients who did not receive prophylactic DLI or maintenance sorafenib after allo-HSCT as control group.All the patients were in full donor chimerism,minimal residual disease(MRD)and negative state of FLT3-ITD mutation before receiving prophylactic DLI or sorafenib maintenance therapy.None of the patients had acute GVHD when they received prophylactic DLI or sorafenib maintenance therapy.ResultsTwenty-four patients received maintenance sorafenib treatment after transplantation(group A);twelve patients received prophylactic DLI(group B)after transplantation and thirty-two patients in control group(group C).There were no significant differences among the three groups in gender,age,karyotype,pretransplant disease status and other transplant and disease characteristics.The median follow-up time of 68 patients was 615 days(79-2016 days),and the 2-year predicted OS,LFS and CIR were 78.4%,73.1% and 22.7%,respectively.Among the three groups,2-year OS,LFS and CIR in patients with maintenance sorafenib(group A)were 95.8%,95.8% and 4.2%,respectively,in patients with prophylactic DLI(group B)were 75%,66.7% and 25.0%,respectively,and in control group(group C)were 67.0%,60.9% and 33.4%,respectively.The 2-year OS and LFS in group A were significantly lower than the other two groups(A vs B,OS: P=0.043,LFS: P=0.031;A vs C,OS: P=0.018,LFS: P=0.007).The 2-year CIR in group A was significantly lower than that in group C(P=0.017),but there were had no significant difference between groups A and B and groups B and C(A vs B,P=0.197;B vs C,P=0.611).The 2-year OS and LFS were not significantly different between groups B and C(OS: P=0.664;LFS: 0.631).The 2-year estimated NRM posttransplant was 4.6% in all patients and was no statistical difference among the three groups(A vs B vs C was 0% vs 8.3% vs 6.8%,P=0.336)。Before sorafenib maintenance therapy or prophylactic DLI,there was no significant difference between the three groups in the incidence of acute GVHD(A vs B P=0.725;A vs C P=0.961;B vs C P=0.559).In group A,2 patients developed acute GVHD and 19 patients developed chronic GVHD after sorafenib treatment.In group B,8 patients developed acute GVHD after prophylactic DLI,and 6 patients developed chronic GVHD.After receiving the prophylactic treatment,the incidence of acute GVHD in group B was significantly higher than that in group A(P<0.001),but there was no statistically significant difference in the incidence of chronic GVHD between the two groups(P=0.287).After allo-HSCT,the 1-year cumulative incidence of mild chronic GVHD in group A,group B and group C was 75.0%,33.3% and 55.0%,respectively.The cumulative incidence of mild chronic GVHD in group A was significantly higher than other two geoup(A vs B,P=0.014;A vs C,P=0.020),but there was no statistically significant difference between groups A and B or between groups B and C(P=0.067 and P=0.421).After allo-HSCT,the cumulative incidence of severe chronic GVHD at 1 year was similar among the three groups(8.3% vs 22.2% vs 13.5% in group A vs group B vs group C,P=0.218).ConclusionIn summary,our study shows that both prophylactic DLI and sorafenib maintenance therapy can be effective and relatively safe interventions after hematopoietic stem cell transplantation in patients with FLT3-ITD-positive AML.Compared with prophylactic DLI,sorafenib maintenance therapy has shown better results in efficacy and safety,and may be a more suitable treatment option after allo-HSCT in patients with FLT3-ITDpositive AML in the future. |
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