Balasubramanian, P.

Abstract Rationale Acute cellular rejection (ACR) within first-year post-lung transplantation has important implications for prognosis. Calcineurin inhibitors (CNI), including tacrolimus or cyclosporine, along with cell cycle inhibitors (CCI) and steroids, remain the standard immunosuppression regimen post-transplant. Although tacrolimus is used as the primary CNI, target therapeutic levels vary across recipients due to adverse effects and tolerability, sometimes requiring switching over to Cyclosporine. We hypothesized that ACR within the first year is associated with switching CNI from Tacrolimus to Cyclosporine. Methods We performed a cross-sectional study of 255 adult lung transplant recipients between June 2019 to November 2024 at Mayo Clinic, Florida. Demographics, induction regimens, CNI type and their levels (average low and high levels) were compared between the 2 groups. The institutional maintenance immunosuppression regimen is Tacrolimus, Mycophenolate Mofetil (MMF) and prednisone, but could be switched to Cyclosporine if the previous regimen is not tolerated. The primary outcome was ACR <1 year diagnosed based on biopsy and/or clinical criteria. Comparisons between groups were performed using Chi-Square test for categorical variables and t-test or Wilcoxon Rank sum test for continuous variables. Multivariable regression analysis was performed with ACR <1 year as the outcome to adjust for the confounders. Results Our cohort included 255 lung transplant recipients with median age of 63 years, 61% Male, 84% Caucasians, 88% bilateral lung transplant (Further details elucidated in Table 1). A total of 173 (67%) out of 255 patients had ACR <1 year. The group with ACR < 1 year had higher proportion of Interstitial Lung Disease (ILD) (81% vs 68%, p = 0.044), use of Basiliximab for induction (70% vs 55%, p = 0.018), and cyclosporine instead of tacrolimus (23% vs 11%, p = 0.027). Group with ACR <1 year also had higher Antibody Mediated Rejection (AMR) < 1year (15% vs 6.1%, p = 0.041) and higher CLAD (BOS 0p-3: 43% vs 25.6%, p = 0.033) compared to the group without ACR < 1 year (Table 1.1). Multivariate regression analysis showed ILD (adjusted odds ratio, aOR 2.84, 95% CI 1.31 - 6.27, p = 0.008) and use of cyclosporine (aOR 2.55, 95% CI 1.07 - 6.78, p = 0.034) as independent predictors of ACR < 1 year (Table 2). Conclusions The presence of ACR < 1 year was associated with the use of Cyclosporine over Tacrolimus as a maintenance regimen. Also, ACR < 1year was associated with higher AMR and CLAD. Further prospective studies are needed to study this long-term given its significant prognostic implications. This abstract is funded by: Not Applicable

Abstract Background Lung transplantation remains the accepted treatment modality of choice for life-threatening advanced lung disease due to established benefits of improving survival and functional status of the patients. However, the annual mortality of lung waitlist candidates remains high, reflecting ongoing donor-recipient mismatches and prolonged wait times. Modalities such as extracorporeal membrane oxygenation (ECMO) have been effectively used as a “bridge to transplant” (BTT) in high-risk patients on waitlist. Objective To evaluate trends in ECMO utilization, waitlist dynamics, and outcomes among lung transplant candidates between 2018 and 2024, with emphasis on the use of ECMO as a bridge to transplantation. Methods We conducted a retrospective chart review of all ECMO runs performed between 2018 to 2024 at the Mayo Clinic Florida Hospital. Among these, patients who underwent evaluation for lung transplantation were identified, and their waitlisting patterns, transplant outcomes, and peri-transplant ECMO status were described. Results Between 2018 and 2024, a total of 348 ECMO runs were recorded among 293 patients. Annual ECMO runs increased steadily from 17 in 2018 to 83 in 2024 (2019: 33, 2020: 30, 2021: 61, 2022: 56, 2023: 68, 2024: 83). Out of these patients, 142 underwent evaluation for lung transplantation and 133 (93.67%) were placed on the waitlist. Among waitlisted patients, 105 (78.9%) were listed before ECMO initiation, 23 (17.3%) during ECMO, and 5 (3.8%) after decannulation. Waitlist outcomes included 116 (87.2%) transplanted, 16 (12.0%) deaths before transplant, and 1 (0.8%) clinical improvement precluding transplant. Among 116 transplanted patients, 36 patients (31.03%) received ECMO as a bridge to lung transplantation. The annual patients bridged with ECMO demonstrated a progressive rise: 1 (2019), 3 (2020), 9 (2021), 6 (2022), 9 (2023), and 8 (2024). Among these 36 patients, 29 (80.56%) remained on ECMO support in the immediate post-transplant period. At the latest follow-up, mortality among BTT recipients was 9 (25%). Conclusion ECMO utilization has expanded substantially over the past several years reflecting its expanding role in supporting critically ill patients. There has been increased utilization of ECMO as a bridge to lung transplantation in order to support high risk candidates awaiting donor organs. The post-transplant mortality among BTT recipients was 25%, which highlights the importance of peri-transplant management to optimize long-term outcomes in this high-risk cohort. This abstract is funded by: None

Abstract Introduction: The data on outcomes comparing lung transplantation with ABO-identical versus ABO-compatible blood group is limited. Composite Allocation Score(CAS) was introduced on March 9th, 2023, and has considered additional points for the difficult-to-match blood group. We aimed to study the trend and outcomes of patients who underwent lung transplants with ABO identical versus compatible blood groups. Methods: We queried the United Network of Organ Sharing (UNOS) database of those who underwent lung transplantation between 10/1/1987 to 3/31/2024 and compared the outcomes between those who had ABO-identical vs ABO-compatible blood groups. Combined organ transplants and recipients age <18 were excluded. Results: A total of 50,406 patients were included in our study, out of which 4,111 (8.15%) were ABO-compatible and 47,347 (91.85%) were ABO-identical. Among the recipient demographics, the ABO-compatible group compared to the ABO-identical group showed a lesser lung allocation score (40 ± 16 vs 42 ± 16), but higher A-blood group (59% vs 38%), obstructive lung disease (38% vs 33%), CAS (49 ± 13 vs 47 ± 10), mechanical ventilator support pre-transplant (6.2% vs 5.2%), need for ex-vivo lung perfusion (9.6% vs 5.8%) and listing for single lung transplant (39% vs 34%), all p<0.05. The donors for the ABO-compatible group had a closer distance to the transplant center (205 ± 285 vs 226 ± 265 nautical miles), lesser white race (61% vs 64%), and gender mismatch (30% vs 32%) but higher male gender (64% vs 61%), O-blood group (81% vs 49%) and ethnicity mismatch (45% vs 41%), all p<0.05. The univariate analysis showed a higher 30-day (7.2% vs 5.8%), 1-year (22% vs 19%), and 5-year (54% vs 50%) mortality among patients with ABO-compatible compared to ABO-identical recipients, all p<0.001. However, the adjusted odds ratio of 30-day (0.76, 95% CI 0.36-1.47, p=0.4), 1-year (1.07, 95% CI 0.69-1.66, p=0.7) and 5-year (0.69, 95% CI 0.46-1.05, p=0.081) mortality were not statistically significant with ABO-identical when compared to ABO-compatible group on adjusting to the covariates in the multivariate analysis. The trend of ABO-compatible lung transplantation has been increasing with the introduction of CAS (figure 1). Conclusion: Patients who underwent lung transplantation with the ABO-compatible blood group donor organs had similar outcomes compared to the ABO-identical blood group. The findings of our study reinforce the importance of increasing the use of ABO-compatible organs to enhance the lung transplantation rate, aligning with the observed trend following the introduction of CAS.