| Background and objection:Acute myeloid leukemia(AML)is a common hematologic malignancy,and allogeneic hematopoietic stem cell transplantation(allo-HSCT)is currently the only possible cure for it.But relapse,graft versus-host disease(GVHD),and infections remain important causes of post-transplant mortality.Sorafenib is a tyrosine protein kinase inhibitor(TKI),and our previous studies has shown that sorafenib maintenance therapy post-transplantation can significantly reduce the relapse of leukemia and prolong survival in patients with FLT3-ITD mutation,but its effect on post-transplant opportunistic viral infections remains unclear,especially Epstein-Barr virus(EBV)and cytomegalovirus(CMV)infections.Use of kinase inhibitors such as dasatinib and imatinib might increase the risk of EBV and CMV infections.Therefore,we designed this study to investigate the effect of sorafenib maintenance post-transplantation on the incidence and mortality of EBV and CMV infections in patients with FLT3-ITD acute myeloid leukemia,and further analyzed whether it can get a long-term survival benefit for this type of patients based on the long-term follow-up data of our early clinical trial,and explored the safety and efficacy of sorafenib treatment.MethodsWe collected the clinical data,EBV and CMV infections,treatment and survival of 202 patients included in a clinical trial conducted in seven hospitals in China.SPSS software 25.0 and R4.0.1 were used for statistical analysis,all statistics were double-sided tests,and the difference was considered statistically significant at P<0.05.The primary endpoint was EBV and CMV infections within 3 years post-transplantation.Secondary endpoints included the cumulative incidences of relapse,non-relapse mortality(NRM),overall survival(OS),leukemia-free survival(LFS)and graft-versus-host disease(GVHD)-free/relapse-free survival(GRFS)at 3 years.Results202 patients were assigned to sorafenib maintenance(n=100)or non-maintenance(control,n=102).Median extended follow-up post-transplantation was 36.8(range,2.5-67.1)months.The 3-year cumulative incidences of EBV-DNAemia and EBV-associated diseases were 24.0%(95%Cl:16.1-32.8%)and 5.0%(1.8-10.6%)in the sorafenib group,and 24.5%(16.6-33 2%)and 5.9%(2.4-11.6%)in the control group(P=0.937;P=0.771).The 3-year cumulative incidences of CMV-DNAemia and CMV-associated diseases were 56.0%(45.6-65.1%)and 8.0%(3.7-14.4%)in the sorafenib group,and 52.9%(42.7-62.1%)and 8.8%(4.3-15.3%)in the control group(P=0.997;P=0.826).The 3-year cumulative mortality of EBV-and CMV-associated diseases was 0.0%(0.0-0.0%)and 2.0%(0.4-6.4%)in the sorafenib group,and 1.0%(0.1-4.8%)and 2.0%(0.4-63%)in the control group(P=0.322,P--0.980).The 3-year cumulative incidences of relapse,NRM,OS,LFS and GRFS were 13.0%,11.1%,79.0%,75.9%and 65.8%in the sorafenib group,and 34.8%,12.7%61.4%52.5%and 46.6%in the control group,respectively(P<0.001,P=0.656,P=0.005,P<0.001,P--0.003).The reconstitution of T lymphocyte subsets,B lymphocytes,and natural killer cells at+1,+3,+6,+9,+12 months post-transplantation were similar between the two groups(all P>0.05).Conclusions1.Sorafenib maintenance post-transplantation in FLT3-ITD~+AML patients does not increase the incidence and mortality of EBV and CMV infections,and has no effect on immune reconstitution after transplantation in these patients.2.Sorafenib maintenance post-transplantation can reduce the relapse of leukemia in FLT3-ITD~+AML patients without affecting non-relapse mortality,thereby prolonging survival and improving patient outcomes,demonstrating a favorable safety and efficacy. |
