Letermovir prophylaxis for cytomegalovirus is associated with risk of post-transplant lymphoproliferative disorders after haploidentical stem cell transplantation

Letermovir prophylaxis for cytomegalovirus is associated with risk of post-transplant lymphoproliferative disorders after haploidentical stem cell transplantationCytomegalovirus (CMV) and Epstein-Barr virus (EBV) emerge as the most frequently reactivated opportunistic viruses after haploidentical stem cell transplantation (haplo-SCT). [1][2]][3] As members of the family of herpesviruses, CMV and EBV are reported to be linked to causing clinical manifestations, resulting in co-infection rates ranging from 10% to 32.7%. 4,5dditionally, CMV treatment coincides with EBV reactivation, potentially affecting the progression of EBV reactivation and EBV-associated diseases. 6,7Letermovir prophylaxis effectively reduces CMV infection after haplo-SCT. 8,9However, its impact on EBV remains unclear.This study compared letermovir recipients (letermovir group) to a control group receiving standard polymerase chain reaction (PCR)-guided pre-emptive therapy (non-letermovir group) in two independent cohorts.In both cohorts, letermovir significantly reduced clinically significant CMV infection and refractory CMV infection within 180 days after the transplant.While the incidence of EBV viremia was similar in the two groups, letermovir recipients exhibited higher peak EBV titers and had an increased risk of post-transplant lymphoproliferative disorder (PTLD) within the first 180 days.In both univariate and multivariate analyses, the use of letermovir was significantly linked to a higher risk of PTLD.These findings indicate that while letermovir prophylaxis is highly effective in preventing CMV complications after haplo-SCT, it may also be associated with an increased risk of PTLD, highlighting the need for caution and further research to explore this potential link in clinical practice.Patients were divided into two cohorts based on transplant date.Cohort 1 (June 2022 to December 2022) included letermovir-treated haplo-SCT patients in whom letermovir use depended on a patient's choice and drug availability.Cohort 2 (January 2023 to June 2023) (NCT05656599) included haplo-SCT patients who regularly received letermovir and met our inclusion criteria as part of our registered clinical trial (clinicaltrials.govNCT05656599).Non-letermovir controls received PCR-guided therapy, matched 1:1 to letermovir patients by gender, age, and disease via propensity score matching.Inclusion criteria were first haplo-SCT, age over 14 years, and letermovir started within 28 days and continued to 100 days after the transplant.Patients with genetic metabolic disorders, bone marrow fibrosis or who died early within 28 days were excluded.Patients in whom CMV or EBV reactivated before letermovir or within 7 days of letermovir administration were also excluded.