Multicenter analysis of immunosuppressive medications on the risk of malignancy following adult solid organ transplantation.

Objective: This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types. Methods: This is a retrospective cohort study from a multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and post-transplant malignancy. Results: A total of 5,591 patients, 6,142 transplanted organs, and 517 post-transplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia. Conclusion: Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients.

Impact of Delayed Chest Closure on Surgical Site Infection After Lung Transplantation.

BACKGROUND: Delayed chest closure is an increasingly used approach in the management of bleeding and hemodynamic instability after lung transplantation. We sought to evaluate the impact of delayed chest closure on surgical site infection. METHODS: We performed a single-center retrospective cohort study and included adult patients who received a lung transplant at our center between January 1, 2010, and July 31, 2014. We defined surgical site infection as a thoracotomy incision wound or pleural space infection. Follow-up was complete through 6 months after transplantation. We used logistic regression models to examine the impact of delayed chest closure on surgical site infection and to identify other potential risk factors. RESULTS: During the study period, 67 of the 232 transplant procedures (29%) required delayed chest closure, and surgical site infection developed in 22 recipients (9%). Among the patients with surgical site infection, 18 experienced a wound infection, and 8 experienced a pleural space infection; 4 experienced concomitant wound and pleural space infection. Among the 67 who underwent delayed chest closure, 13 patients (19%) experienced a surgical site infection compared with 9 of the 165 patients (5%) who underwent primary closure (p = 0.001). In multivariate analysis, delayed chest closure was an independent risk factor for surgical site infection. CONCLUSIONS: Although delayed chest closure may have an important role in the immediate management of recipients of a lung transplant, it is an independent risk factor for surgical site infection, and this is associated with increased morbidity.

The impact of pre-transplant allosensitization on outcomes after lung transplantation.

BACKGROUND: Allosensitization can be a significant barrier to transplantation for some patients, and previous studies suggested that pre-transplant allosensitization was associated with worse outcomes after lung transplantation. However, human leukocyte antigen (HLA) antibody testing has evolved significantly over the past 10 years, and current assays are highly sensitive and specific. METHODS: We examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays in this retrospective, single-center study of 304 adult transplant recipients between January 1, 2006, and December 31, 2012. We accepted donor organs for allosensitized patients if a virtual crossmatch was compatible with all previously identified antibodies. RESULTS: In univariate and multivariate Cox proportional hazards models, pre-transplant allosensitization, the calculated panel reactive antibody, and the number of pre-transplant HLA antibodies were not associated with the development of acute cellular rejection, lymphocytic bronchiolitis, donor-specific HLA antibodies, chronic lung allograft dysfunction, or graft failure. CONCLUSIONS: Pre-transplant allosensitization does not adversely affect outcomes after lung transplantation when the potentially reactive HLAs are avoided in the donor by a virtual crossmatch with the recipient.

Antibody-mediated Rejection in Lung Transplantation.

There has been increasing awareness of antibody-mediated rejection (AMR) as an important cause of graft failure after lung transplantation in recent years. However, the diagnostic criteria for pulmonary AMR are not well defined. All four tenets of AMR in kidney and heart transplantation, graft dysfunction, complement component deposition, circulating donor-specific antibodies (DSA), and histopathologic changes consistent with AMR, are infrequently present in lung transplantation. Nonetheless, the lung transplant community has made important progress recognizing cases of AMR and developing a definition. However, AMR is often refractory to therapy resulting in graft failure and death. In this review, we discuss the progress and challenges in the diagnosis and therapeutic options for pulmonary AMR. In addition, we briefly examine emerging paradigms of C4d-negative AMR and chronic AMR, and conclude that significant progress is needed to mitigate the effects of humoral immune responses after lung transplantation.