Lung transplant physician-researchers on the medical staff at Baylor University Medical Center at Dallas (Baylor Dallas), part of Baylor Scott & White Health, attended the 2024 American Transplant Congress (ATC) in Philadelphia, PA. ATC is the most prominent annual forum for the entire international transplant community to present new findings and engage with colleagues on the latest trends in the field. ATC is the joint meeting of the AST and the American Society of Transplant Surgeons (ASTS).
At ATC 2024, Michael Duncan, MD, chief of Pulmonary Medicine at Baylor Dallas, was named to the American Society of Transplantation (AST) Thoracic and Critical Care Executive Committee.
The latest findings from key research studies intended to improve lung transplant outcomes are described below:
Donor-derived cell-free DNA to assess lung allograft status
Donor-derived cell-free DNA (dd-cfDNA) assessment is emerging as a game-changing technology for non-invasive monitoring of allograft status. When a transplant is injured, the damaged cells release DNA into the peripheral circulation, and this DNA can be detected in serum or plasma samples. cfDNA is commonly used for prenatal screening and dd-cfDNA shows promise for assessing the graft status for various solid tumors. There is great interest in understanding how dd-cfDNA can be used to monitor lung transplants since current monitoring methods require bronchoscopy, which is an invasive procedure. Physician-researchers associated with Baylor Dallas are contributors to a large study to evaluate dd-cfDNA and lung transplant outcomes in the diverse population of patients who access care from Baylor Scott & White in North and Central Texas, and the researchers described early results of a focused substudy at ATC 2024.
Primary graft dysfunction (PGD) is an acute ischemia/reperfusion injury of the allograft and is the leading cause of early mortality after a lung transplant. To understand if dd-cf-DNA is a biomarker of PGD status, the researchers performed a retrospective analysis of dd-cfDNA levels in blood samples collected at follow-up visits from patients who experienced mild-or-moderate PGD (Grades 0 and 1; n=15) or severe PGD (Grades 2 and 3; n=10) at 72 hours post-transplant. Overall, the dd-cf-DNA levels were highest in blood samples collected during the first 90 days after transplant relative to samples collected later in the first year. Given the small sample size, this ongoing study did not yet meet statistical significance criteria, but there was a numerical trend toward elevated dd-cfDNA in patients with severe PGD.
According to Todd Grazia, MD, chief of Transplant Pulmonology at Baylor Dallas, “This study highlights that the interpretation of dd-cf-DNA results can be complex and may rely on consideration of other markers and clinical parameters as part of a suite of precision medicine tools. We are enrolling patients prospectively and look forward to more thoroughly evaluating dd-cf-DNA as a candidate marker of acute PGD status. We will also be interested to see if a higher acute dd-cf-DNA signal correlates to a higher incidence of negative outcomes such as chronic rejection.” The Baylor Dallas researchers are also contributing to the Trifecta-Lung study, which will evaluate additional cell-free DNA markers for allograft monitoring.
Long-term oral prophylaxis with itraconazole outperforms short-term inhaled amphotericin for preventing fungal infections after lung transplant
Invasive fungal infections (IFIs) are an important risk factor for lung transplant recipients because, unlike other solid organ transplants, the lung is directly exposed to airborne pathogens. However, more research is needed to compare prophylactic strategies to reduce fungal infections.
Dr. Grazia says, “The ISHLT guidelines suggest using antifungal prophylaxis, but there is a lot of variation among practices. Here in Texas, there are many endemic fungal pathogens and high mold spore counts, so we wanted to optimize our prophylactic regimen.”
The transplant team at Baylor Dallas was previously using short-term inhaled amphotericin (30 days) with the rationale that this regimen should prevent infection at the anastomosis, which is an at-risk area during healing. Dr. Grazia says, “This short-term inhaled regimen protects the allograft during a critical period, but may not effectively prevent later infections or distant infections, which may also impact transplant success. For this reason, we shifted our prophylactic regimen to a long-term oral therapy. We chose itraconazole, which is a well-established antifungal that can be easily obtained at a low cost for our patients. The current study was designed to tell us which regimen performs better.”
At ATC 2024, the physician-researchers presented the results of a retrospective review of 203 patients treated either with short-term inhaled amphotericin (n=108) or long-term oral itraconazole (n=95). They found a 26% reduction in IFI incidence in the itraconazole group compared to the amphotericin group (76.9% vs. 56.8%; p=0.002) and a longer time to IFI (p=0.009). When the data were separated by pathogen, the itraconazole group outperformed the amphotericin group for Aspergillus spp., Penicillium spp., yeast, and other IFIs. Itraconazole was well-tolerated and there were even fewer discontinuations for intolerance than in the amphotericin group (12% vs 3.2%, p=0.019).
Dr. Grazia says, “This was a remarkable result, especially given the modest sample size of this retrospective study. We are pleased that a long-term oral prophylactic regimen that is easy to obtain, affordable, and well-tolerated also outperforms our historical approach to antifungal prophylaxis.”
Transplant Services at Baylor Dallas
Lung transplant at Baylor Dallas is performed in the Baylor Scott & White Annette C. and Harold C. Simmons Transplant Institute, a world-renowned high-volume center for multi-organ transplant care and one of the largest transplant programs in the nation. The lung transplant program at Baylor Dallas was established 25 years ago, and the multi-disciplinary team of pulmonary care experts prides itself on personalized care and leadership in research.
