Faculty Bibliography

INTRODUCTION/BACKGROUND:Sensitization to human leukocyte antigens has long posed an obstacle to organ transplantation. With desensitization protocol refinement, new drug development, and organ allocation policy changes, access to transplant for sensitized patients has never been greater. Yet in spite of these advances the problem of donor specific antibody remains incompletely solved, and many patients remain poorly served by the therapies that do exist. Area covered: Imlifidase is a new drug with a mechanism of action that enables it to transiently yet efficiently eliminate donor specific antibody over a much more rapid time course than any heretofore existing therapy. This unique property suggests that imlifidase may have far reaching potential for patients in whom donor specific antibodies may preclude successful transplantation. Below follows a review of the clinical experience with imlifidase to date as well as a discussion the transplant applications that eagerly await the availability of this novel agent. Expert opinion: Imlifidase is a first-in-class pharmaceutical agent that safely and efficiently cleaves IgG, and holds promise to be a game changer for sensitized patients in need of lifesaving organ transplants.

BACKGROUND:The use of direct acting antivirals (DAA) has expanded transplantation from hepatitis C viremic donors (HCV-VIR). Our team has conducted an open-label, prospective trial to assess outcomes transplanting HCV-viremic hearts. Glecaprevir/Pibrentasvir (GLE/PIB) was our sole DAA. METHODS:Serial quantitative hepatitis C virus (HCV) RNA PCR was obtained to assess HCV viral titers. Between January 2018 to June 2019, a total of 50 recipients were transplanted. Of these, 22/50 (44%) were from HCV-VIR, the remaining 28 from non-viremic (HCV NON-VIR) donors. An 8 week course of GLE/PIB was initiated at 1 week post-transplant. RESULTS:There was no difference in demographic or clinical parameters between groups. All 22 recipients of HCV-VIR transplants became viremic. GLE/PIB was effective in decreasing viremia to undetectable levels by 6 weeks post-transplant in all patients. The median time to first undetectable HCV quantitative PCR was (4.3 weeks, IQR: 4-5.7 weeks). All patients demonstrated sustained undetectable viral load through 1 year follow up. There was no difference in survival at one year between HCV NON-VIR 28/28: (100%) vs. HCV-VIR 21/22 (95%) recipients. CONCLUSIONS:Our center reports excellent outcomes in transplanting utilizing hearts from HCV-VIR donors. No effect on survival or co-morbidity was found. An 8 week GLE/PIB course was safe and effective when initiated approximately 1 week post-transplant.

BACKGROUND:Several studies have described improved survival with double lung transplantation (DLT) compared to single lung transplantation (SLT) in pulmonary fibrosis. To avoid the innate selection bias of including patients exclusively listed for SLT or DLT, this study analyzed those deemed appropriate for either procedure at time of listing. METHODS:All consecutive adult lung transplants for idiopathic pulmonary fibrosis (IPF) provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (N=11), or patients listed only for SLT (N=1834) or DLT (N=2372) were excluded. Group stratification was based on the ultimate procedure (SLT vs DLT). Group propensity matching was performed based on 24 recipient/donor characteristics. Recipient demographics, donor demographics, and outcomes were compared between groups. RESULTS:During the study period, 45% (974/2179) and 55% (1205/2179) of patients ultimately received SLT and DLT, respectively. After propensity matching, 466 matched patients remained in each group. SLT patients were less likely to require prolonged (>48 hours) ventilator support than DLT patients. There was also a trend towards reduced rates of post-transplant renal failure and hospital length of stay in SLT recipients. Whether analyzed by time of listing or time of transplant, survival was similar between groups. CONCLUSIONS:In recipients concurrently listed for SLT and DLT, overall survival was similar regardless of the eventual procedure. These data suggests that the previously purported survival advantage for DLT may purely represent selection bias, and should not preclude the use of SLT in appropriately-selected IPF patients.

Background: Clinical trials have demonstrated the safety of utilizing hepatitis C viremic donors (HCV+) to expand the donor pool through transplantation into hepatitis C naive recipients (HCV-). However, there has been a lack of enthusiasm to of er HCV+ pancreas grafts to HCV- recipients. We of ered HCV- pancreas patients the option to list for HCV+ donor organs.
Material(s) and Method(s): Patients undergoing pancreas transplant evaluation had informed consent by a transplant physician to receive HCV+ donor organs. We ensured patients had pharmacy coverage for post-transplant HCV anti-retroviral therapy prior to listing. In our early experience, 4 of our 8 transplant recipients elected to list for HCV+ donor organs.
Result(s): In the first 8 months, the average time to transplant from listing was 41 days for patients with standard listing and 21 days for patients listing for HCV+ organs (p<0.05). Of note, 2 of the 4 HCV- recipients were blood type AB and had shorter match time due to their blood type. For all HCV+ donors, COD was anoxia/drug OD, all were HCV antibody and NAT positive, PHS IR, and national imports, with average rank of 3 on the match run. All HCV- donors were local donors with average rank of 21 on the match run. HCV+ donors were younger (28 years) in contrast to HCV- donors (35 years). All recipients have excellent graft function with no signif cant dif erences in complications, LOS, or readmissions.
Conclusion(s): Utilization of HCV+ pancreas donors has allowed our patients increased access to high quality pancreas donors with signif cantly shorter wait times

Desensitization using plasma exchange can remove harmful antibodies prior to transplantation and mitigate risks for hyperacute and severe early acute antibody-mediated rejection. Traditionally, the use of plasma exchange requires a living donor so that the timing of treatments relative to transplant can be planned. Non-HLA antibody is increasingly recognized as capable of causing antibody-mediated renal allograft rejection and has been associated with decreased graft longevity. Our patient had high-strength non-HLA antibody deemed prohibitive to transplantation without desensitization, but no living donors. As the patient was eligible to receive an A2 ABO blood group organ and was willing to accept a hepatitis C positive donor kidney, this afforded a high probability of receiving an offer within a short enough time frame to attempt empiric desensitization in anticipation of a deceased donor transplant. Fifteen plasma exchange treatments were performed before the patient received an organ offer, and the patient was successfully transplanted. Hepatitis C infection was treated posttransplant. No episodes of rejection were observed. At one-year posttransplant, the patient maintains good graft function. In this case, willingness to consider nontraditional donor organs enabled us to mimic living donor desensitization using a deceased donor.

BACKGROUND:The national opioid epidemic may have expanded the donor pool for lung transplantation, but concerns remain regarding infectious risks and allograft function. This study compared donor/recipient characteristics, outcomes, and reasons for organ discard between overdose death donors (ODD) and all other mechanism-of-death donors. METHODS:Data on adult lung transplants from 2000-2017 were provided by the Scientific Registry of Transplant Recipients. Pulmonary allografts used in multiple organ transplantations were excluded. Donor/recipient demographics, outcomes, and organ discard were analyzed with regards to ODD since 2010. Discard analysis was limited to donors who had at least one organ transplanted but their pulmonary allografts discarded. RESULTS:From 2010-2017, 7.3% (962/13,196) of lung transplantations were from ODD, over a 3-fold increase from the 2.1% (164/7,969) in 2000-2007. ODD were younger but more likely to have a history of smoking, hepatitis C, or an abnormal bronchoscopy finding. Overall survival was similar between ODD and non-ODD groups. ODD of discarded pulmonary allografts were younger and more likely to be hepatitis C positive, but were less likely to have a history of smoking than their non-ODD counterparts. CONCLUSIONS:Rates of ODD utilization in lung transplantation have increased in accordance with the opioid epidemic, but there remains a significant pool of ODD pulmonary allografts with favorable characteristics that are discarded. With no significant difference in survival between ODD and non-ODD recipients, further expansion of this donor pool may be appropriate and pulmonary allografts should not be discarded based solely on ODD status.

BACKGROUND:Anastomotic complications occur in 7% to 18% of lung transplant recipients, among which airway dehiscence (AD) is particularly catastrophic. Using multi-institutional registry data, this study compared preoperative recipient/donor risk factors and outcomes in patients with and without AD and analyzed the effect of extracorporeal membrane oxygenation (ECMO) on the incidence of AD. METHODS:Data on adult lung transplants from 2007 to 2017 were provided by the Scientific Registry of Transplant Recipients. Patients receiving isolated lobar transplantation and patients with unknown AD status were excluded. Multivariable logistic regression identified independent risk factors for AD. Kaplan-Meier curves and log-rank tests describe mortality and graft survival. RESULTS:Of 18 122 lung transplants, 275 (1.5%) experienced AD. While the incidence of ECMO steadily increased from 0.7% to 5.9% over the study period, the incidence of AD remained relatively constant. Multivariable analysis revealed recipient male gender and prolonged ( > 48 hours) posttransplant mechanical ventilation as independent predictive factors for AD, while advanced donor age and single left lung transplant were protective factors. Recipient chronic steroid use, recipient diabetes, donor diabetes, and donor smoking history were not predictive of AD. Mortality and graft failure were significantly worse in the AD group. CONCLUSIONS:Despite increased ECMO utilization, the incidence of AD has remained stable. Multiple independent risk factors for AD were identified and poor postoperative outcomes confirmed. However, many known impediments to wound healing such as recipient chronic steroid use, recipient and donor diabetes, and donor smoking were not identified as risk factors for AD, reinforcing the critical role of technical performance.

BACKGROUND:The national opioid epidemic has expanded the donor pool for heart transplantation, but concerns remain regarding infectious risk and allograft function. This study compared donor and recipient characteristics, outcomes, and reasons for organ discard between overdose-death donors (ODDs) and donors with all other mechanism of death. METHODS:Data on adult cardiac transplants from 2010 to 2017 were provided by the Scientific Registry of Transplant Recipients. Cardiac allografts used in multiple organ transplantations were excluded. Recipient and donor characteristics and organ discard were analyzed with regard to ODDs. Kaplan-Meier curves and log-rank tests described mortality survival. RESULTS:A total of 1,710 of 15,904 (10.8%) cardiac transplantations were from ODDs, approximately a 10-fold increase from 2000 (1.2%). ODDs were more frequently older than 40 years of age (87.2% vs 70.1%; p < 0.001), had higher rates of substance abuse, were more likely hepatitis C positive (1.3% vs 0.2%; p < 0.001), and less frequently required inotropic support at the time of procurement (38.4% vs 44.8%; p < 0.001). Overall survival was not different between the groups (p = 0.066). Discarded ODD allografts were more likely to be hepatitis C positive (30.8% vs 5.3%; p < 0.001) and to be identified as conveying increased risk by the Public Health Services (63.3% vs 13.2%; p < 0.001), but they were less likely to be discarded because of a diseased organ state (28.2% vs 36.1%; p < 0.001). CONCLUSIONS:Rates of ODDs have increased corresponding with the worsening opioid epidemic. Even though ODDs have higher rates of hepatitis C, cardiac allograft quality indices are favorable, and recipient outcomes are similar when compared with non-ODDs, a finding indicating that greater use of this donor pool may be appropriate.

Objective: Anastomotic complications occur in 77%-18% of lung transplants, but no large multi-institutional analyses to determine risk factors for airway dehiscence (AD) exist. Using national registry data, we compared pre-operative recipient/donor risk factors and post-operative outcomes in patients with and without AD.
Method(s): Data on adult lung transplants between 2007 and 2017 were provided by the Scientifc Registry of Transplant Recipients. Recipient/donor demographics were compared with regards to AD, and multivariable logistic regression identifed independent risk factors for AD. Kaplan-Meier curves and log-rank tests described mortality and graft survival.
Result(s): Two hundred and seventy-fve/18,122 recipients (1.5%) experienced AD. These recipients were more often male (71.6% vs. 59.6%, P < 0.001), obese (20.1% vs. 15.6%, P = 0.041), transplanted from intensive care unit (17.5% vs. 1 1 . 0 % , P = 0.001), and mechanically ventilated (11.6% vs. 6.9%, P = 0.002). AD was not associated with recipient steroid use (51.9% vs. 47.7%, P = 0.194) or lung disease diagnosis group. Donor diabetes (8.0% vs. 7.0%, P = 0.482) and donor smoking (7.4% vs. 9.0%, P = 0.449) were also not associated with AD. Patients with AD were more likely to have received bilateral lungs (78.5% vs. 68.3%, P < 0.001) and less likely to have received a single left lung (6.5% vs. 17.3%, P < 0.001). Cold ischemia time between 2 and 4 hours was less common in the AD group (17.2% vs. 23.7%, P = 0.013). Multivariable analysis revealed recipient obesity and donor gunshot death as independent predictive factors for AD, while donor age >40 and single left lung transplant were negative predictive factors (Table SA10-1). Mortality and graft failure were both signifcantly higher in the AD group (Fig. SA10-1).
Conclusion(s): We identifed independent risk factors for AD and confrmed poor post-operative outcomes. However, many known impediments to wound healing such as chronic steroid use, diabetes, and smoking did not appear to be associated with AD