Nuances in the interpretation and utility of donor-derived cell-free DNA in lung transplantation following allogeneic hematopoietic stem cell transplantation - Case report.

Respiratory complications following allogeneic HSCT can lead to severe morbidity and mortality. Lung transplantation (LT) is a potential treatment for select patients with late-onset non-infectious pulmonary complications post-HSCT. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for monitoring the health of allografts following LT. However, its utility in a multi-genome setting of LT after HSCT has not yet been clinically validated. Here we describe a case of a 75-year-old, male patient who underwent single-lung transplantation for BOS related to chronic GVHD and presented with persistently elevated dd-cfDNA levels. In a surveillance biopsy, the patient was diagnosed with mild acute cellular rejection at three months. The patient's lung function remained stable, and the reported dd-cfDNA levels decreased after the rejection episode but remained elevated above levels that would be considered quiescent for LT alone. In this unique setting, as 3 different genomes contributed to the dd-cfDNA% reported value, valuable insight was obtained by performing further analysis to separate the specific SNPs to identify the contribution of recipient, lung-donor, and HSCT-donor cfDNA. This study highlights the potential utility of dd-cfDNA in the multi-genome setting of lung transplant post-HSCT, nuances that need to be considered while interpreting the results, and its value in monitoring lung rejection.

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

A pandemic of acute respiratory distress syndrome-role of lung transplant in coronavirus disease-2019-associated respiratory failure.

Lung transplantation may be appropriate, and may offer benefit only to a carefully selected subset of morbidly ill patients afflicted by coronavirus disease-2019. Identifying the appropriate recipient for the allocation of scarce resources, by safely navigating through the challenges that are unique to lung transplantation for coronavirus disease-2019-associated acute respiratory distress syndrome, demands a conscientious and meticulous approach. Categorizing the respiratory failure in coronavirus disease-2019 may facilitate the process of evaluation for the purpose of transplant. The progress in rescue transplants over the past two decades has greatly improved our ability to successfully perform high-risk lung transplantation.

Pathophysiology of respiratory failure and physiology of gas exchange during ECMO.

Lungs play a key role in sustaining cellular respiration by regulating the levels of oxygen and carbon dioxide in the blood. This is achieved by exchanging these gases between blood and ambient air across the alveolar capillary membrane by the process of diffusion. In the microstructure of the lung, gas exchange is compartmentalized and happens in millions of microscopic alveolar units. In situations of lung injury, this structural complexity is disrupted resulting in impaired gas exchange. Depending on the severity and the type of lung injury, different aspects of pulmonary physiology are affected. If the respiratory failure is refractory to ventilator support, extracorporeal membrane oxygenation (ECMO) can be utilized to support the gas exchange needs of the body. In ECMO, thin hollow fiber membranes made up of polymethylpentene act as blood-gas interface for diffusion. Decades of innovative engineering with membranes and their alignment with blood and gas flows has enabled modern oxygenators to achieve clinically and physiologically significant amount of gas exchange.