Baz, Maher A.

Abstract Rationale This Registry was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to arrest the rate of FEV1 decline (FEV1 decline) and prolong survival in lung allograft recipients with Bronchiolitis Obliterans refractory to standard of care therapy. Methods After IRB approval, 258 lung transplant recipients were enrolled from 20 US lung transplant centers. Subjects were assigned to ECP treatment (ECPRx) (i.e., 24 procedures over 6 months) at or a few months after enrollment based on spirometric criteria. Maintenance ECPRx (mECP) was at the discretion of managing clinicians. Rate of FEV1 decline in mL/month (FEV1 decline) was compared between 6 months prior to and 6 & 12 months after ECPRx initiation using linear mixed effects models. Time 0 for survival was set as the start of ECPRx for generation of Kaplan-Meier curves. Hazard Ratios (HR) with 95% confidence intervals (lower-upper) were generated using Cox Proportional Hazards Regression to characterize significant (p < 0.05) independent associations of mECP and/or any other covariates (i.e., demographic, operative, enrollment site, spirometric ) and survival. Results An 89% (78%-96%) decrease in the FEV1 decline was observed 12 months after ECPRx initiation in 191 participants assigned to ECPRx. FEV1 decline (-164 mL/month: 144-185) was greater (p < 0.001) in participants who expired within six months of Time 0 (n = 28) vs participants (-111 mL/month: 101-120) who died six months after Time 0 (n = 77). Of 159 participants who survived for at least six months after ECPRx initiation, 40 participants without mECP, who had up to 24 ECPRx (ECPRx: n = 19), had a lower survival HR: 2.43(1.75-3.4) (p < 0.001) relative to 119 participants who received mECP (ECPRx: n = 86)(see Figure). The response to ECPRx (% Change in FEV1 decline prior to and 6 months after 1st ECP) was similar between subcohorts (No mECP: -81 decrease vs mECP: -85%, p = 0.3). The association of mECP persisted after multivariate adjustment HR 1.8 (1.8-2.7)(p = 0.002) using significant covariates: FEV1 HR 0.37 (0.3-0.5), FEV1 decline HR 0.001 (0.001-0.04), Male Gender HR 2.4 (1.7-3.4); Reflux Disease HR 1.8 (1.2-2.8); Coronary Disease HR 1.8 (1.2-2.7). Conclusions This analysis indicates that mECP is independently associated with enhanced survival most likely due to attenuation of relapse six months after ECP initiation based on similar initial response to ECPRx. A risk-adjusted, control cohort is being pursued to facilitate submission of a scientifically rigorous petition to CMS to expand the ECP National Coverage Decision to include BOS predicated on CMS 2024 scientific guidelines. This abstract is funded by: Therakos Inc

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 Treating Mycobacterium avium complex (MAC) infection pre‐lung transplant (LT) can be challenging to treat, given prolonged therapy and side effects. The impact of pre‐transplant MAC treatment on recurrence and outcomes post‐LT remains unclear, especially in patients with interstitial lung disease (ILD) who have a median survival of less than 2 years. Methods We performed a retrospective cohort study of adult LT patients at the Mayo Clinic who had positive MAC sputum cultures pre‐LT. The cohort was stratified and compared based on the type of treatment (complete, partial, or no treatment) for MAC pulmonary infection. The primary outcome was MAC recurrence post‐LT, and secondary outcomes were mortality, FEV‐1, and FVC at 1‐year post‐LT. Results Among the cohort of 47 patients, 9 (19.1%) were partially treated and 11 (23.4%) were completely treated for MAC infection pre‐LT. Post‐transplant MAC pulmonary infection recurrence occurred in eight (17%) of the total cohort, with four (14.8%) in the non‐treated, four (44.4%) in the partially‐treated, and none (0%) in the completely treated patients ( p = 0.026). There was no difference in mortality in patients who had MAC recurrence post‐transplantation (13% vs. 9.7%, p > 0.9) and those who were completely or partially treated, compared to non‐treated (0% vs. 13% vs. 13%, p > 0.9). The FEV1 and FVC at 1‐year post‐LT did not differ by the pre‐transplant treatment or post‐transplant MAC recurrence status. Conclusion The role of treatment for MAC infection pre‐transplant is questionable, especially in patients with diseases like ILD who may not have enough wait time to complete therapy.

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.

Objective To observe the effect of naloxone on the lung function of potential lung transplant donors with neurogenic pulmonary edema. Design and Interventions Donors aged 16 to 55 years without any factors to contraindicate lung donation (pneumonia, pulmonary contusion, etc) were included. Ventilator settings were standardized to a tidal volume of 10 to 12 mL/kg, an FiO 2 of 0.40, and a respiratory rate that kept PCO 2 between 35 and 45 mm Hg. Chest physiotherapy, nebulizer treatments, and frequent suctioning were undertaken. Baseline arterial blood gas analysis and an oxygen challenge were performed. The patients were then given 8 to 10 mg of naloxone. Oxygen challenges and arterial blood gas analyses were repeated every 4 to 6 hours. The data were analyzed by using a paired t test, and each patient served as his or her own control. Setting These interventions were performed on the 19 LifeQuest donors who met the set criteria from July 2002 to July 2004. Results The PaO 2 on the oxygen challenge immediately after administration of naloxone increased from 329 (SD 177) to 363 (SD 191) mm Hg, although the increase from baseline was not significant. The PaO 2 from the second oxygen challenge (median time, 7 hours after administration of naloxone) increased to 413 (SD 177) mm Hg ( P < .01).