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Background: Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common.Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation. Methods:We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018. Results: Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for lowgrade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects. Conclusion: Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted. K E Y W O R D S cytomegalovirus, heart transplantation, letermovir, lung transplantation 2 of 6 | ARYAL et AL. 1 | INTRODUC TI ON Cytomegalovirus (CMV) infection is a common complication among thoracic organ transplant recipients and often results in increased morbidity and mortality. 1 Ganciclovir and its prodrug, valganciclovir, are used for antiviral prophylaxis after thoracic organ transplantation in recipients with moderate or high risk of CMV infection. They are also the first-line drugs used in the treatment of CMV infection, and both share the same mechanism of action through inhibition of viral DNA polymerase. While these medications are effective, their use is limited by adverse effects and the risk for development of antiviral resistance. It is estimated that 7%-35% of thoracic organ transplant recipients develop leukopenia with 3%-15% of them affected by neutropenia, which can be associated with an increased risk of infection and death. 2 The hematologic complications of valganciclovir/ganciclovir therapy are often compounded by concomitant medication use in transplant recipients. Moreover, therapeutic failure may occur due to the development of resistance mediated by mutations in the genes UL97 and UL54. 3...

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Summary Although induction therapy has been used in heart transplantation for many years, its role has not been fully elucidated. Early safety concerns relating to OKT3 or intensive lymphocyte‐depleting regimens have largely been addressed by modern induction protocols using rabbit antithymocyte globulin (rATG [Thymoglobuline® or ATG‐Fresenius]) and interleukin‐2 receptor antagonist (IL‐2RA) agents, but although the number of randomized controlled studies has expanded there are still gaps in the evidence base. Rejection prophylaxis may be somewhat more effective with rATG than IL‐2RA agents, but this has not been proven conclusively. Administration of induction therapy to support delayed introduction of calcineurin inhibitors in patients at risk of renal dysfunction is relatively well documented and widely used. Increasingly, it is recognized that sensitized patients and individuals with primary graft function are suitable candidates for induction therapy, and the possibility that rATG may inhibit cardiac allograft vasculopathy is also of considerable interest. Until the question of whether rATG is associated with increased risk of infection, routine prophylaxis is advisable. IL‐2RA induction has an excellent safety profile. Dosing rATG according to lymphocyte count reduces cumulative dose without compromising efficacy. Further controlled trials are required to determine when and how to deploy induction most effectively following heart transplantation.