Letermovir prophylaxis in solid organ transplant-Assessing CMV breakthrough and tacrolimus drug interaction.

BACKGROUND: Valganciclovir is the preferred drug for cytomegalovirus (CMV) prophylaxis in solid organ transplantation. A limitation to its use is profound myelosuppression. Letermovir is a new agent approved for CMV prophylaxis in hematopoietic stem cell transplantation and is associated with less toxicity. This study aims to assess the effectiveness and safety of letermovir in solid organ transplantation. METHODS: A single-center, matched cohort study was performed on 31 transplant recipients who were converted from valganciclovir to letermovir from November 2017 to June 2020. The primary outcome was the rate of CMV breakthrough infections while on prophylaxis. Secondary outcomes included rate of leukopenia, doses of immunosuppression, rejection, non-CMV infection, and renal function. Statistical analyses of continuous variables included the student's t-test, ANOVA test, and Wilcoxon Signed Rank test. Categorical data were analyzed with chi-square test and Fisher's Exact test. RESULTS: There was no difference in the rate of CMV breakthrough between patients on letermovir (8.7%) and valganciclovir (13.5%), (P = .7097). After conversion to letermovir, patients required lower tacrolimus doses at -3.34 mg (SD-1.3, P = .0273), between conversion and day 7. Transplant Infectious Disease The median difference in tacrolimus trough concentrations from conversion to day seven was 9.1 ng/ml [4.9, 16.95] (P = .0002). Leukopenia improved by 1.8 109/L [1.08, 4.85] (P < .0001). CONCLUSIONS: Patients converted from valganciclovir to letermovir did not show an increased rate of CMV breakthrough compared to a historical, matched cohort of patients remaining on valganciclovir. A significant drug interaction was noted with tacrolimus, leading to a recommendation to reduce the dose by 40-50% upon initiation of letermovir.

Factor VIIa administration in orthotopic heart transplant recipients and its impact on thromboembolic events and post-transplant outcomes.

Recombinant, activated factor VIIa (rFVIIa) is used during cardiac surgeries to mitigate refractory coagulopathic bleeding. The purpose of this study was to examine whether rFVIIa use in orthotopic heart transplant (OHT) recipients was associated with a higher incidence of thromboembolic (TE) events compared to patients who did not. A single-center, retrospective, cohort study was performed on OHT recipients who received rFVIIa for refractory coagulopathic bleeding from January 2013 to December 2015. Patients were evaluated for up to 6 months after transplantation and assessed for TE events, rejection, readmissions, graft survival, and patient survival. Categorical variables were analyzed using the Chi square test while student's t or ANOVA testing was utilized for continuous variables. Of the 62 patients who met inclusion criteria, 27 patients received rFVIIa, and 35 patients were selected for the control group. The overall incidence of TE events was not significantly different between patients who received rFVIIa compared to patients in the control group (14.8% vs 11.4%) (p = 0.69). Within 14 days, 14.81% of rFVIIa patients suffered a TE event compared to 5.7% of the control group (p = 0.23). Rejection, readmissions, graft survival, and patient survival were not significantly different at any time points. Use of rFVIIa in heart transplantation showed no difference in the overall rate of TE events, however, there was a nonsignificant trend toward higher risk of early TE development in the rFVIIa group compared to the control group.

Outcomes of Lung Transplantation for Cystic Fibrosis in the Setting of Extensively Drug-Resistant Organisms.

INTRODUCTION: Since the largest study on extensively drug-resistant organisms and lung transplantation in patients with cystic fibrosis, there have been innovations and advancements in the treatment of Pseudomonas aeruginosa. RESEARCH QUESTION: What differences exist for patients with cystic fibrosis with a history of extensively drug-resistant infections who undergo lung transplantation despite treatment advances with antimicrobial therapy? STUDY DESIGN: Two-center, retrospective, cohort study conducted in 44 patients with cystic fibrosis chronically infected with extensively drug-resistant organisms who received a lung transplant from January 2008 through August 2016. Patients in the resistant cohort were chronically infected with pan-resistant P aeruginosa, polymyxin-sensitive only, or sensitive to 2 antibiotic classes (polymyxin plus one other); remaining patients with more susceptible P aeruginosa or no P aeruginosa remained in the control cohort. The primary outcome is a composite of patient survival, retransplantation, chronic lung allograft dysfunction, and acute rejection 12 months posttransplant. Categorical variables were analyzed using χ2 testing. The independent samples t test was utilized for continuous variables. RESULTS: There was no difference in the primary outcome (40% vs 37%, P = .831). Differences between patient survival (84% vs 95%, P = .487), the incidence of acute rejection (20% vs 33%, P = .323), and the incidence of chronic lung allograft rejection (12% vs 5%, P = .441) were not different between groups. DISCUSSION: Recipients chronically infected with an extensively resistant P aeruginosa had similar outcomes compared to those infected with more sensitive organisms.

Maintenance Belatacept-Based Immunosuppression in Lung Transplantation Recipients Who Failed Calcineurin Inhibitors.

BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS: Single-center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR. Patients were evaluated at fixed time points before and after belatacept initiation. Primary outcome was incidence of acute cellular rejection (ACR). Secondary outcomes included incidence of infection, chronic lung allograft dysfunction (CLAD) progression, death, change in mean arterial pressure, and estimated glomerular filtration rate. RESULTS: Eleven LTRs received belatacept with a mean of 246 (91-1064) days of follow-up after conversion. Four were changed to belatacept for thrombotic thrombocytopenic purpura, 3 for posterior reversible encephalopathy syndrome, 2 for recurrent ACR, 1 for CLAD, and 1 for renal-sparing. ACR was not different before and after belatacept (P = 0.17). Mean estimated glomerular filtration rate was significantly higher postbelatacept (32.53 vs 45.26, P = 0.04). Mean incidence of infections (24.4% vs 16.0%, P = 0.55) and mean arterial pressure (97.5 vs 92.1 P = 0.38) were not different. Progression of CLAD occurred in 2 patients. At the end of follow-up, 7 of 11 patients were alive. CONCLUSIONS: Belatacept-based ISR appear to produce reasonable results in LTRs who fail CNI-based ISR. Larger prospective trials appear warranted in lung transplantation.