Abstract
Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative approach for childhood acute leukemia. Infection is the leading cause of death in allo-HSCT recipients after transplantation. The risk of CMV reactivation in CMV seropositive patients after haploidentical transplantation (Haplo-HSCT) is 80%, which increases the risk of death and acute graft-versus-host disease (aGVHD). This study aims to analyze the efficacy and safety of letermovir in preventing CMV infection in children with leukemia after haploidentical transplantation.
Methods: Fifty-three children with leukemia who underwent haploidentical transplantation at Hebei Yanda Lu Daopei Hospital from October 1, 2022 to October 31, 2024 were collected and randomly assigned to the experimental group and the control group. The conditioning regimens were all myeloablative.The sources of stem cells were G-CSF-mobilized bone marrow + peripheral blood stem cells in 50 cases, G-CSF-mobilized peripheral blood stem cells in 3 cases. Patients were divided into two groups based on whether letermovir was prophylactically administered after transplantation: the control group (no prophylactic letermovir after transplantation) and the experimental group (prophylactic letermovir after transplantation). The median follow-up time was 19.77 months (ranging from 27.20 months to 1.73 months).
Result：The control group included 30 cases, with a male-to-female ratio of 15:15. The median age at onset was 7.00 years, including 19 cases of acute lymphoblastic leukemia and 11 cases of acute myeloid leukemia. Nine patients were MRD positive before transplantation (median: 0.03%). The median number of MNCs reinfused was 10.30×108/kg, and the median number of CD34+ cells was 5.00×106/kg. The experimental group included 23 cases, with a male-to-female ratio of 15:8. The median age at onset was 9.00 years, including 9 cases of acute lymphoblastic leukemia, 12 cases of acute myeloid leukemia, and 2 cases of acute mixed cell leukemia. One patient had 11.37% in bone marrow FCM monitoring before transplantation. The median number of MNCs reinfused was 19.55×108/kg, and the median number of CD34+ cells was 12.00×106/kg. The median time of letermovir application in the experimental group was +1 day , and the median duration of letermovir application was 100 days. All 30 patients in the control group achieved engraftment of white blood cells, with a median engraftment time of 16.00 days . Three patients did not achieve engraftment of platelets, with a median engraftment time of 13.00 days . During the follow-up period, 6 patients had hematological relapse and 7 died. All 23 patients in the experimental group achieved engraftment of white blood cells, with a median engraftment time of 14.00 days , and all achieved engraftment of platelets, with a median engraftment time of 11.00 days. The incidence of CMV at 100 days after transplantation was 26.09%, which was lower than that in the control group (26.09% vs. 43.33%, p = 0.151). The incidence of EBV at 100 days was lower than that in the control group (8.07% vs. 13.04%, p = 0.580). The incidence of aGVHD was 39.13%, which was lower than that in the control group (39.13% vs. 73.33%, p = 0.009), and the incidence of (Ⅱ°-Ⅳ°) was lower than that in the control group (8.70% vs. 46.67%, p = 0.003). During the follow-up period, 2 patients relapsed,Both achieved complete remission after treatment. During the follow-up period, 2 patients died, both due to infection. The estimated 3-year survival rate (equivalent to disease-free survival rate) was 80.00%, slightly higher than that in the control group (80.00% vs. 76.67%, p = 0.34), and the estimated 3-year relapse rate was 9.57%, lower than that in the control group (9.57% vs. 22.03%, p = 0.292).
Conclusion: For children with acute leukemia who undergo haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), the use of letermovir for the prevention of cytomegalovirus (CMV) infection after transplantation is effective. It does not increase the incidence of Epstein-Barr virus (EBV) infection or the incidence of grade II-IV acute graft-versus-host disease (aGVHD), and it improves the 3-year survival rate and reduces the 3-year recurrence rate.
