Purpose The effect of SARS-CoV-2 vaccination on de novo donor specific antibodies (dnDSA) in lung transplant recipients (LTRs) is unknown. We reviewed dnDSA results following SARS-CoV-2 vaccination in LTRs based on SARS-CoV-2 IgG response. Methods LTRs were tested for SARS-COV-2 Multi-target IgG at 3 and 6 months post-vaccination. LTRs who received at least 1 dose of SARS-CoV-2 vaccine between 12/01/2020 to 07/01/2021 were included in this retrospective review. We compared patients based on anti-spike (S-IgG) results. Results We reviewed 55 LTR charts with S-IgG results. Only 24 (44%) developed S-IgG by 6 months after vaccination. Differences between S-IgG positive and negative groups are shown in the table. Those with positive S-IgG were further from transplant, had lower mycophenolate doses, more likely to have had COVID infection pre-vaccination, and had lower rates of hypogammaglobulinemia. Only 3 patients (5.5%) developed dnDSA after vaccination; all were S-IgG positive. One had history of antibody mediated rejection (AMR), while another was initially negative for dnDSA at 6 weeks post-vaccination, but turned positive at 7 months (low level Class II DSA). One patient who had prior DSA developed clinical rejection (AMR) with Class II dnDSA (DR7) and significant rise in prior DSA (DR53, DQ2) to >20,000 MFI at 6 months (negative at 3 months) post-vaccine in the setting of new viral infection. Another patient was excluded from this study as he died of AMR and dnClass II DSA (DQ8 > 10,000 MFI, DQ6, DR4 within 5 days of dose) 2 months after his first Pfizer/BioNTech dose, but before 3 month S-IgG testing. Conclusion In our cohort, dnDSA after SARS-CoV-2 vaccination was uncommon but observed in patients who developed S-IgG response. The single AMR case occurred late and may be related to infection. In the excluded patient with acute AMR early after vaccine, correlation to S-IgG is unknown as the patient did not survive to 3 months. Further studies are needed to determine the impact of additional vaccine doses and long-term outcomes and immune responses.

Purpose Prostacyclins are used to treat advanced pulmonary arterial hypertension as continuous intravenous or subcutaneous infusions. In the right clinical setting, parenteral Prostacyclins can be transitioned to newer oral Prostacyclins. There is a dearth of published guidance for this transition and is limited to inpatient setting. We present our experience with transitioning patients with WHO group 1 pulmonary arterial hypertension from parenteral Treprostinil to oral Treprostinil in the outpatient setting. Methods 6 patients with WHO group 1 pulmonary arterial hypertension on stable doses of intravenous or subcutaneous Treprostinil for at least 6 months were transitioned to oral Treprostinil as per published protocol albeit at a slower rate of transition at 6 ng/kg/min per day Results All the 6 patients were successfully transitioned from Parenteral Treprostinil to oral Treprostinil and 4 remain on oral therapy for 1- 4 years. The reasons for transition include complications of central line, side effects related to parenteral Prostacyclins and personal preference. Two patients deteriorated over 6-12 months after the transition requiring transition back to parenteral Treprostinil. No deterioration in PAH was noted during the transition. High 6 MWD, High WHO FC (1/2) and normal RV function on parenteral Prostacyclins are associated with successful results. Conclusion In the right clinical setting, patients can be successfully transitioned from parenteral Treprostinil to oral Treprostinil and this can be accomplished safely in the outpatient setting.

Purpose Medication non-compliance after cardiac transplantation may be improved by simplifying dosing frequency to once-a-day extended-release tacrolimus, potentially reducing rejection rate and improving patient outcomes. Of the 2 distinct proprietary formulations for extended-release tacrolimus that are FDA approved for renal transplant patients, Meltdose tacrolimus tablets (LCP-Tacro or LCPT) has enhanced bioavailability, including in rapid metabolizers. There is limited data supporting the use of extended release tacrolimus in heart transplant recipients. Here we report initial safety and efficacy findings with extended-release tacrolimus in this population. Methods In an ongoing, phase II, single-center, open-label study (NCT03373227), 20 de novo adult heart transplant recipients have been enrolled to receive LCPT. Primary endpoints included incidence of rejection and graft failure. Secondary endpoints included compliance, incidence of adverse effects, infections, re-admissions, and survival. Therapeutic tacrolimus levels were monitored for overall drug compliance. A CYP3A5 genotype sub-study has been added to examine the associations between genotype and efficacy and safety. Results Demographics and findings are shown in Table 1. During a median post-transplant follow-up of 22 weeks (range 2-45), no serious drug related adverse events were observed and no safety issues identified. Percent of time in therapeutic range was consistent with low incidence of rejection; 2 patients had an episode of treated rejection, which resolved with steroid therapy. Conclusion Our findings demonstrate favorable early safety and efficacy profile of LCPT in heart transplant recipients. Medication non-compliance after cardiac transplantation may be improved by simplifying dosing frequency to once-a-day extended-release tacrolimus, potentially reducing rejection rate and improving patient outcomes. Of the 2 distinct proprietary formulations for extended-release tacrolimus that are FDA approved for renal transplant patients, Meltdose tacrolimus tablets (LCP-Tacro or LCPT) has enhanced bioavailability, including in rapid metabolizers. There is limited data supporting the use of extended release tacrolimus in heart transplant recipients. Here we report initial safety and efficacy findings with extended-release tacrolimus in this population. In an ongoing, phase II, single-center, open-label study (NCT03373227), 20 de novo adult heart transplant recipients have been enrolled to receive LCPT. Primary endpoints included incidence of rejection and graft failure. Secondary endpoints included compliance, incidence of adverse effects, infections, re-admissions, and survival. Therapeutic tacrolimus levels were monitored for overall drug compliance. A CYP3A5 genotype sub-study has been added to examine the associations between genotype and efficacy and safety. Demographics and findings are shown in Table 1. During a median post-transplant follow-up of 22 weeks (range 2-45), no serious drug related adverse events were observed and no safety issues identified. Percent of time in therapeutic range was consistent with low incidence of rejection; 2 patients had an episode of treated rejection, which resolved with steroid therapy. Our findings demonstrate favorable early safety and efficacy profile of LCPT in heart transplant recipients.

Purpose While induction immunosuppression is commonly employed by heart transplant (HT) centers, its impact on patient survival remains controversial. Optimal use of a risk stratification methodology balancing risk versus benefit to determine induction is also unknown. Our team sought to analyze the impact of a risk stratified approach to induction on outcomes after HT. Methods Historically, our program has utilized basiliximab routinely on HT recipients. In 2017, we implemented a risk stratified approach to induction categorized into four groups. Stratification was based on age, race, re-transplant status, virtual crossmatch data, pre-transplant C1q data, panel reactive antibodies, and need for pre-transplant desensitization. Low risk patients received no induction, moderate risk basiliximab, specialty risk anti-thymocyte globulin and high risk plasmapheresis/bortezomib/IVIG/anti-thymocyte globulin. We performed a retrospective analysis of adult HTs performed in 2016 (historical cohort) and 2017 (risk stratified cohort). One-year outcomes compared included mortality, biopsy proven ACR and AMR, DSA, graft dysfunction, and infectious complications. Results Baseline demographics were similar between groups. The low risk category represented 91% of the risk stratified cohort. Use of basiliximab decreased by 65.2% in risk stratified group. Incidence of acute cellular rejection (ACR) was similar in both cohorts and there were no cases of antibody mediated rejection (AMR). There was a trend towards higher DSA development in the historical cohort. While the trend for treated CMV was higher in the risk-stratified cohort, there was no difference in rate of infections requiring hospitalizations. There was no significant difference in survival. Conclusion This personalized approach to induction in HT led to similar rejection, mortality and infectious outcomes, in addition to cost savings from decreased overall use of induction therapy. While induction immunosuppression is commonly employed by heart transplant (HT) centers, its impact on patient survival remains controversial. Optimal use of a risk stratification methodology balancing risk versus benefit to determine induction is also unknown. Our team sought to analyze the impact of a risk stratified approach to induction on outcomes after HT. Historically, our program has utilized basiliximab routinely on HT recipients. In 2017, we implemented a risk stratified approach to induction categorized into four groups. Stratification was based on age, race, re-transplant status, virtual crossmatch data, pre-transplant C1q data, panel reactive antibodies, and need for pre-transplant desensitization. Low risk patients received no induction, moderate risk basiliximab, specialty risk anti-thymocyte globulin and high risk plasmapheresis/bortezomib/IVIG/anti-thymocyte globulin. We performed a retrospective analysis of adult HTs performed in 2016 (historical cohort) and 2017 (risk stratified cohort). One-year outcomes compared included mortality, biopsy proven ACR and AMR, DSA, graft dysfunction, and infectious complications. Baseline demographics were similar between groups. The low risk category represented 91% of the risk stratified cohort. Use of basiliximab decreased by 65.2% in risk stratified group. Incidence of acute cellular rejection (ACR) was similar in both cohorts and there were no cases of antibody mediated rejection (AMR). There was a trend towards higher DSA development in the historical cohort. While the trend for treated CMV was higher in the risk-stratified cohort, there was no difference in rate of infections requiring hospitalizations. There was no significant difference in survival. This personalized approach to induction in HT led to similar rejection, mortality and infectious outcomes, in addition to cost savings from decreased overall use of induction therapy.

Hepatitis C virus (HCV) nucleic acid test (NAT) positive cardiac donors are rarely utilized given increased morbidity and mortality risk after orthotopic heart transplantation (OHTx). However, impact of highly effective HCV antivirals on donor-derived HCV outcomes remain unclear. We report successful transplantation with a high risk HCV NAT-positive donor into a HCV antibody negative OHTx recipient, and a sustained virologic response at 1 month of anti-HCV therapy.