Clinical Transplantation最新文献_第8页

Solid Organ Malignancy After Pancreas Transplantation: A Four Decade Single-Center Experience 胰腺移植后实体器官恶性肿瘤：四十年的单中心研究

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-11 DOI: 10.1111/ctr.70381

Michael G. Megaly, Todd DeFor, Xianghua Luo, Michael Dryden, Joseph Sushil Rao, Matthew Wright, David Mathews, Karthik Ramanathan, Vanessa Humpreville, Erik B. Finger, Raja Kandaswamy, Abraham J. Matar

Background

Although advances in pancreas transplantation have improved patient survival, prolonged immunosuppression has increased the risk of post-transplant malignancies. This study aimed to examine the incidence, risk factors, and long-term outcomes of solid organ malignancies in pancreas transplant recipients at a single center.

Methods

All adult pancreas transplants between February 1, 1983, and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK).

Results

1729 pancreas transplant recipients were included with a median follow-up of 23 years. During this period, 152 (8.8%) developed a non-skin, non-hematologic malignancy at a median time of 12.6 years after transplant, with a cumulative incidence of 13% (95% CI 11%–16%) at 30 years post-transplant. The most common malignancies were colorectal (14.1%), renal cell (13.0%), breast (13.0%), and lung (9.7%) cancers. Functioning graft status (HR 0.67, 95% CI 0.47–0.95, p = 0.024), maintenance corticosteroid use (HR 1.51, 95% CI 1.00–2.27, p = 0.051), and transplant era (p = 0.015) were risk factors for development of a solid organ malignancy. Overall survival following malignancy diagnosis was poor, with a 10-year post-diagnosis survival rate of 24% (95% CI 17%–33%). No recipient or transplant-related factors were independently associated with mortality after malignancy diagnosis.

Conclusion

Solid organ malignancies constitute a substantial late complication in pancreas transplant recipients, with corticosteroid exposure and graft longevity as key risk factors. These findings underscore the need for long-term cancer surveillance and tailored immunosuppressive strategies in this population.

尽管胰腺移植技术的进步提高了患者的生存率，但长期的免疫抑制增加了移植后恶性肿瘤的风险。本研究旨在研究单一中心胰腺移植受者实体器官恶性肿瘤的发生率、危险因素和长期预后。方法回顾1983年2月1日至2023年12月31日在明尼苏达大学进行的所有成人胰腺移植手术，包括单独胰腺移植（PTA）、胰肾联合移植（SPK）和肾移植后胰腺移植（PAK）。结果纳入1729例胰腺移植受者，中位随访23年。在此期间，152例（8.8%）患者在移植后12.6年的中位时间内发展为非皮肤、非血液系统恶性肿瘤，移植后30年的累积发病率为13% （95% CI为11%-16%）。最常见的恶性肿瘤是结直肠癌（14.1%）、肾细胞癌（13.0%）、乳腺癌（13.0%）和肺癌（9.7%）。移植物功能状态（HR 0.67, 95% CI 0.47-0.95, p = 0.024）、维持皮质类固醇使用（HR 1.51, 95% CI 1.00-2.27, p = 0.051）和移植时间（p = 0.015）是发生实体器官恶性肿瘤的危险因素。恶性肿瘤诊断后的总体生存率较差，诊断后10年生存率为24% （95% CI 17%-33%）。没有受体或移植相关因素与恶性肿瘤诊断后的死亡率独立相关。结论实体器官恶性肿瘤是胰腺移植患者的重要晚期并发症，皮质类固醇暴露和移植物寿命是主要危险因素。这些发现强调了对这一人群进行长期癌症监测和量身定制的免疫抑制策略的必要性。

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引用次数: 0

Donation after Circulatory Death Donors Are Associated With Increased 1-Year Mortality After Lung Transplantation: A UNOS-Based Risk Stratification Study 循环性死亡后的捐赠与肺移植后1年死亡率增加相关：一项基于unos的风险分层研究

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-11 DOI: 10.1111/ctr.70399

Amit Banga, Brandon A. Guenthart, Song Zhang, John W. MacArthur, Gundeep S. Dhillon

Background

The use of donation after circulatory death (DCD) donors has significantly increased in recent years. The current study sought to risk-stratify transplants where DCD donors are utilized.

Methods

We reviewed the UNOS database for adult patients who underwent lung transplantation (LT) using DCD donors between 2017 and 2022 (n = 948, 6.31% of all LT). One-year mortality was the primary dependent variable.

Results

The proportion of DCD donors is increasing (3.7% in 2017 to 7.6% in 2022, p < 0.001) and is associated with significantly higher 1-year mortality (13.9% vs. 10.7% among recipients of brain dead donors; p = 0.003). On Cox proportional hazard analysis with bootstrap validation, recipient age > 65 years (adjusted hazards ratio, 95% CI: 1.51, 1.05–2.2; p = 0.028), admission to the ICU at the time of transplant (2.11, 1.34–3.31; p = 0.001), estimated GFR < 75 mL/min/1.73 m² at the time of transplant (1.81, 1.23–2.67; p = 0.003), and organ out of body time >7 h (2.02, 1.39–2.94; p < 0.001) are associated with 1-year mortality. A composite variable, the recipient risk score, based on the number of above risk factors, is strongly associated with 1-year mortality.

Conclusions

The utilization of DCD donors is associated with worse 1-year mortality after LT. The recipient risk score based on the four simple-to-use recipient and procedure-related variables strongly predicts outcomes.

背景近年来，循环死亡（DCD）供者捐献的使用显著增加。目前的研究试图对使用DCD供体的移植进行风险分层。方法：我们回顾了UNOS数据库中2017年至2022年间使用DCD供体接受肺移植（LT）的成年患者（n = 948，占所有LT的6.31%）。1年死亡率是主要的因变量。结果DCD供体比例呈上升趋势（2017年为3.7%，2022年为7.6%,p < 0.001），且与较高的1年死亡率相关（脑死亡供体受者为13.9% vs. 10.7%, p = 0.003）。在采用bootstrap验证的Cox比例风险分析中，受者年龄>； 65岁（校正风险比，95% CI: 1.51, 1.05-2.2; p = 0.028）、移植时入住ICU （2.11, 1.34-3.31; p = 0.001）、移植时估计GFR <； 75 mL/min/1.73 m2 （1.81, 1.23-2.67; p = 0.003）、器官出体时间>；7 h （2.02, 1.39-2.94; p < 0.001）与1年死亡率相关。一个复合变量，即基于上述危险因素数量的受者风险评分，与1年死亡率密切相关。结论DCD供体的使用与lt后较差的1年死亡率相关。基于四个简单使用的受体和程序相关变量的受体风险评分强有力地预测了结果。

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引用次数: 0

Drone-Assisted Organ Transport: A Scoping Review of Clinical, Regulatory, and System Readiness 无人机辅助器官运输：临床，监管和系统准备的范围审查

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-11 DOI: 10.1111/ctr.70398

Robson G. Gilmour, Mekhola Hoff

Organ transport remains a critical determinant of transplant success, with delays during transfer prolonging cold ischemia time (CIT) and increasing the risk of delayed graft function or organ discard. Uncrewed aerial vehicles (UAVs) have emerged as a potential means to enhance the speed, predictability, and resilience of transplant logistics. This scoping review synthesized global evidence from 2010 to 2025 across biomedical, engineering, and regulatory domains, mapping research within six key themes: time sensitivity and clinical evidence, integration with preservation and perfusion technologies, technological and infrastructural readiness, regulatory and ethical frameworks, economic and environmental feasibility, and public and professional preparedness. Case studies from North America, Europe, and Asia demonstrate that UAVs can safely deliver donor organs while maintaining temperature and structural stability, with successful clinical transplantation reported. Their current value lies primarily in short-range transfers where direct routing and rapid handover are feasible; however, advances in heavy-lift aircraft, autonomous traffic management, and connected perfusion systems may soon enable longer, more complex missions. Major barriers include restrictions on beyond-visual-line-of-sight (BVLOS) operation, payload and endurance limitations, uncertain liability frameworks, and incomplete hospital-side infrastructure. Future priorities include comparative clinical and economic trials, harmonized international standards, and certified medical air corridors integrated with national allocation systems. With appropriate regulation, interoperability, and clinical validation, drones could become a safe and sustainable extension of existing transplant networks—improving efficiency, equity, and ultimately, patient survival.

器官运输仍然是移植成功的关键决定因素，移植过程中的延迟延长了冷缺血时间（CIT），增加了移植功能延迟或器官丢弃的风险。无人驾驶飞行器（uav）已经成为提高移植物流速度、可预测性和弹性的潜在手段。这一范围综述综合了2010年至2025年生物医学、工程和监管领域的全球证据，绘制了六个关键主题的研究图谱：时间敏感性和临床证据、与保存和灌注技术的整合、技术和基础设施准备、监管和伦理框架、经济和环境可行性，以及公众和专业准备。来自北美、欧洲和亚洲的案例研究表明，无人机可以安全地运送供体器官，同时保持温度和结构稳定性，并有成功的临床移植报道。它们目前的价值主要在于短程传输，在这种情况下，直接路由和快速切换是可行的；然而，重型飞机、自主交通管理和连接灌注系统的进步可能很快就会使更长时间、更复杂的任务成为可能。主要障碍包括对超视距（BVLOS）操作的限制、有效载荷和续航力限制、不确定的责任框架以及医院侧基础设施不完整。未来的优先事项包括比较临床和经济试验、统一的国际标准以及与国家分配系统相结合的经认证的医疗空气走廊。通过适当的监管、互操作性和临床验证，无人机可以成为现有移植网络的安全和可持续的延伸——提高效率、公平性，并最终提高患者的存活率。

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引用次数: 0

Outcomes of Persistent Microvascular Inflammation in Repeated Kidney Allograft Biopsies 反复肾移植活检中持续微血管炎症的结果

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-11 DOI: 10.1111/ctr.70419

Sandesh Parajuli, Adam Bregman, Emily E. Zona, Megan Sokup, Neetika Garg, Weixiong Zhong, Didier Mandelbrot

Background

Microvascular inflammation (MVI) with sum glomerulitis and peritubular capillaritis (g+ptc) ≥ 2 is an integral component of kidney allograft antibody-mediated rejection (AMR). It is unclear what the outcomes are among those with persistent MVI, despite treatment.

Methods

We included all kidney transplant recipients (KTRs) with persistent MVI ≥ 2 on first and second allograft biopsies who had third biopsies within 2 years of the first biopsy. KTRs were categorized into two groups, MVI (+) and MVI (−) on third biopsy. Risk factors for persistent MVI ≥ 2 on third biopsy, and graft survival based on MVI (+) and MVI (−) at last follow-up were outcomes of interest.

Results

A total of 108 KTRs transplanted between 2013 and 2022 fulfilled our selection criteria, 75 (69%) were MVI (+) and 33 (31%) MVI (−). Most baseline characteristics were similar between the groups. In Cox regression analysis, none of the commonly assessed baseline characteristics, Banff scores, or DSA status at first or second biopsy were associated with persistent MVI on the third biopsy. Also, in Cox regression analysis, after adjusting for various characteristics, persistent MVI on third biopsy was not associated with increased or decreased risk for uncensored graft failure (aHR: 0.55, 95% CI: 0.23–1.29; p = 0.17).

Conclusion

The lack of difference in graft outcomes between the AMR patients who were MVI (+) versus MVI (−) on the third biopsy suggests that subsequent response to AMR treatment is less important for prognosis than the initial development of AMR. This reinforces the importance of the prevention of rejection.

微血管炎症（MVI）合并总肾小球炎和小管周围毛细血管炎(g+ptc)≥2是肾移植抗体介导的排斥反应（AMR）的一个组成部分。尽管接受了治疗，但仍不清楚持续性MVI患者的结果如何。方法我们纳入了所有在第一次和第二次同种异体移植活检中MVI持续≥2且在第一次活检后2年内进行了第三次活检的肾移植受者（KTRs）。ktr分为两组，第三次活检时MVI（+）和MVI（-）。第三次活检时持续MVI≥2的危险因素，以及最后随访时基于MVI（+）和MVI（-）的移植物存活是我们感兴趣的结果。结果2013 - 2022年间移植的108例ktr符合我们的选择标准，其中75例（69%）为MVI(+)， 33例（31%）为MVI（-）。两组间的大多数基线特征相似。在Cox回归分析中，通常评估的基线特征、Banff评分或第一次或第二次活检时的DSA状态与第三次活检时的持续性MVI无关。此外，在Cox回归分析中，在调整各种特征后，第三次活检时持续MVI与未审查移植失败风险的增加或降低无关（aHR: 0.55, 95% CI: 0.23-1.29; p = 0.17）。结论第三次活检时MVI（+）与MVI（-）的AMR患者移植物预后没有差异，这表明AMR治疗的后续反应对预后的影响不如AMR的初始发展重要。这加强了预防排斥的重要性。

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引用次数: 0

Neighborhood Deprivation Linked to Medication Level Variability in Liver Transplant Recipients 邻里剥夺与肝移植受者药物水平变化有关

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-11 DOI: 10.1111/ctr.70412

Laila Fozouni, Giuseppe Cullaro, Ann Lazar, Jennifer C. Lai, Sharad I. Wadhwani

Background

Neighborhood deprivation is associated with adverse outcomes post-liver transplantation in pediatric recipients. We examined the association between neighborhood deprivation index (NDI) and medication level variability index (MLVI), T-cell mediated rejection (TCMR), and graft failure/death in adult liver transplant recipients.

Methods

We conducted a retrospective cohort study of 1485 adult liver-transplant recipients with >1 year follow-up. NDI was calculated at the census tract level. MLVI, the standard deviation of ≥3 sequential tacrolimus troughs, was dichotomized at MLVI > 2. Hospitalization was analyzed as a binary variable.

Results

The median age was 65, and 36% were female. In multivariate regression, increased NDI was associated with 20% increased odds of MLVI > 2 between 1–3 years post-transplant (95% CI 1.1–1.3) but not MLVI > 2 between 3–5 years. NDI was associated with a 2.2 times higher hazard of hospitalization between 1–3 years post-transplant (95% CI 1.1–4.4); but not between 3–5 years (HR 1.9, 95% CI 1.0–3.7). NDI was not significantly associated with increased hazard of rejection or graft failure/death. Adjusting for NDI, MLVI > 2 between 1–3 and 3–5 years was associated with a 30% higher hazard of rejection (95% CI 1.1–1.6), and between 1–3 years, a 40% increased hazard of graft failure/death (95% CI 1.2–1.5). We found geospatial hotspots of rejection with positive autocorrelation at Years 1–3 and 3–5 post-transplant (Geary's C 0.97, p = 0.01).

Conclusions

Efforts to understand why individuals from disadvantaged neighborhoods experience poorer immunosuppression adherence may uncover targeted strategies to improve medication adherence for high-risk groups.

背景：邻里剥夺与儿童肝移植后不良后果相关。我们研究了成人肝移植受者的邻里剥夺指数（NDI）、药物水平变异性指数（MLVI）、t细胞介导的排斥反应（TCMR）和移植物衰竭/死亡之间的关系。方法对1485例成人肝移植受者进行回顾性队列研究，随访1年。NDI按人口普查区水平计算。MLVI，即≥3个序贯他克莫司波谷的标准差，在MLVI >； 2处进行二分类。住院率作为二元变量进行分析。结果中位年龄65岁，女性占36%。在多变量回归中，NDI的增加与移植后1-3年内MLVI >； 2的几率增加20%相关（95% CI 1.1-1.3），但与3-5年内MLVI >； 2无关。移植后1-3年内，NDI与住院风险增加2.2倍相关（95% CI 1.1-4.4）；但在3-5年之间没有（HR 1.9, 95% CI 1.0-3.7）。NDI与排斥反应或移植物衰竭/死亡风险增加无显著相关。调整NDI后，1-3年至3-5年的MLVI >； 2与排斥反应风险增加30%相关（95% CI 1.1-1.6）， 1-3年的移植失败/死亡风险增加40% （95% CI 1.2-1.5）。我们发现，在移植后1-3年和3-5年，排斥反应的地理空间热点具有正自相关（Geary’s C = 0.97, p = 0.01）。结论：努力理解为什么弱势社区的个体免疫抑制依从性较差，可能会发现有针对性的策略来提高高危人群的药物依从性。

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引用次数: 0

A Comparison Study of the Roles and Responsibilities, Compensation, and Job Satisfaction of the Medical Directors of Kidney/Kidney-Pancreas, Liver, Lung, and Heart Transplant in the United States 美国肾/肾-胰、肝、肺和心脏移植医疗主任的角色和职责、薪酬和工作满意度的比较研究

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-11 DOI: 10.1111/ctr.70411

Deepika Devuni, Katherine M. Cooper, Alexander Wiseman, Marie M. Budev, Ashrith Guha, Bekir Tanriover, Neeraj Singh

This national cross-sectional survey evaluated the roles, responsibilities, compensation, and job satisfaction of medical directors in adult solid organ transplant programs in the United States. Responses were collected from 210 (34.5%) medical directors representing kidney/kidney-pancreas, liver, heart, and lung transplant centers. The findings reveal wide variation in compensation models and medical director duties across organ types. Kidney/kidney-pancreas directors reported lower compensation, despite leading higher-volume programs. Less than half of respondents reported that these duties were adequately recognized in their compensation. Only 40% of participants perceived their total compensation package as fair, and less than 50% understood how their compensation was determined. A third reported decreased job satisfaction compared to post-fellowship levels. Nearly half of respondents reported symptoms of burnout, with higher rates among women. Perceived fairness of compensation, adequate time with patients, and institutional support for non-clinical duties were associated with job satisfaction, while excessive calls and administrative burden were associated with burnout. These findings suggest more transparent and equitable compensation structures are needed. Incorporating the economic value assessment of transplant providers into institutional planning may strengthen justification for fair compensation models. These data provide a foundation for policy development aimed at enhancing workforce satisfaction and stability across transplant disciplines.

这项全国性的横断面调查评估了美国成人实体器官移植项目中医疗主任的角色、职责、报酬和工作满意度。问卷收集了210名（34.5%）代表肾/肾胰、肝、心和肺移植中心的医疗主任的回复。研究结果显示，不同器官类型的医疗主管在薪酬模式和职责方面存在很大差异。肾脏/肾脏-胰腺主任报告的薪酬较低，尽管他们领导的项目规模较大。不到一半的受访者报告说，这些职责在他们的薪酬中得到了充分的承认。只有40%的参与者认为他们的总体薪酬方案是公平的，不到50%的人了解他们的薪酬是如何确定的。三分之一的人报告说，与获得奖学金后的水平相比，工作满意度有所下降。近一半的受访者表示有倦怠症状，女性比例更高。薪酬公平感、与患者相处的充足时间以及对非临床职责的机构支持与工作满意度相关，而过多的电话和行政负担与职业倦怠相关。这些发现表明，需要更透明和公平的薪酬结构。将移植提供者的经济价值评估纳入制度规划可能会加强公平补偿模式的合理性。这些数据为旨在提高跨移植学科劳动力满意度和稳定性的政策制定提供了基础。

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引用次数: 0

The Role of Albuminuria in Diagnosing and Stratifying Kidney Disease in Heart Transplant Recipients: A KDIGO Criteria-Based Analysis 蛋白尿在心脏移植受者肾脏疾病诊断和分层中的作用：一项基于KDIGO标准的分析

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-10 DOI: 10.1111/ctr.70347

Pedro Caravaca-Pérez, Anthony Salazar Rodriguez, José Jesús Broseta, Eduard Solé Gonzalez, María Ángeles Castel, Juan José Rodriguez, Elena Cuadrado-Payán, Diana Rodriguez-Espinosa, Elena Sandoval, Aleix Cases, Ana García-Álvarez, Marta Farrero

Background

Chronic kidney disease (CKD) is a common but poorly characterized complication in heart transplant (HT) recipients due to limited use of renal damage markers, such as albuminuria. Our aim is to determine CKD prevalence based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, assess CKD risk stratification according KDIGO guidelines, and describe the use of cardiorenal protective drugs in a contemporary HT cohort.

Methods

A cross-sectional, single-center study was conducted in stable HT recipients under follow-up in 2023. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m² (using CKD-EPI) and/or albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Patients were stratified into KDIGO risk categories based on eGFR and UACR thresholds.

Results

Among 207 patients (median age 65 years; 29% women; median time since transplant: 8 years), the median eGFR was 51 mL/min/1.73m², with 58.9% having an eGFR < 60 mL/min/1.73m² and median UACR was 45 (8–173) mg/g, with 57% showing elevated UACR. The prevalence of CKD was 79.2%, with 36 (17.4%) patients exhibiting elevated UACR despite an eGFR ≥ 60 mL/min/1.73m². A total of 23.7%, 19.8%, 21.7%, and 34.8% were classified as low, moderate, high, and very high KDIGO risk categories, respectively. Among patients meeting the CKD criteria, 37.2% were on ACEi/ARBs and 26.2% on SGLT2i.

Conclusions

CKD is highly prevalent in HT recipients, with UACR improving diagnostic accuracy. Over half of patients fell into high-risk KDIGO categories, indicating substantial CKD severity. However, the underuse of renal-protective therapies highlights the need for better alignment with current clinical guidelines.

背景：慢性肾脏疾病（CKD）是心脏移植（HT）受者常见的并发症，但由于肾损害标志物（如蛋白尿）的使用有限，CKD的特征尚不明确。我们的目的是根据肾脏疾病改善全球结局（KDIGO）标准确定CKD患病率，根据KDIGO指南评估CKD风险分层，并描述当代HT队列中心肾保护药物的使用情况。方法：采用横断面、单中心研究，于2023年对稳定的HT受体患者进行随访。CKD被定义为肾小球滤过率（eGFR） 2（使用CKD- epi）和/或白蛋白与肌酐比值(UACR)≥30mg /g。根据eGFR和UACR阈值将患者分为KDIGO风险类别。结果：在207例患者中（中位年龄65岁；29%为女性；移植后中位时间：8年），中位eGFR为51 mL/min/1.73m2, 58.9%为eGFR 2，中位UACR为45 (8-173)mg/g， 57%为UACR升高。CKD患病率为79.2%，尽管eGFR≥60 mL/min/1.73m2，但仍有36例（17.4%）患者UACR升高。分别有23.7%、19.8%、21.7%和34.8%的人被划分为低、中、高和非常高的KDIGO风险类别。在符合CKD标准的患者中，37.2%接受ACEi/ arb治疗，26.2%接受SGLT2i治疗。结论：慢性肾病在HT患者中非常普遍，UACR提高了诊断的准确性。超过一半的患者属于高风险KDIGO类别，表明CKD严重程度很高。然而，肾保护疗法的使用不足突出表明需要更好地与当前的临床指南保持一致。

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引用次数: 0

Belatacept-Based Immunosuppression and Donor-Specific Antibodies in Lung Transplant: A Multi-Institutional Retrospective Study 肺移植中基于belatacept的免疫抑制和供体特异性抗体：一项多机构回顾性研究。

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-10 DOI: 10.1111/ctr.70415

Moustafa Younis, Christopher I. Mederos, Cecelia. M. Miller, Pooja Kumar, Ariana Ishaq, Amy Mu, Cynthia Gries, Victoria Reams, Mohammad A. Aladaileh, Mindaugas Rackauskas, Vaidehi Kaza, Srinivas Bollineni, Fernando Torres, Amir Emtiazjoo, Irina Timofte

Background

Belatacept use in renal transplant is associated with similar graft survival and elimination of preexisting donor-specific antibodies (DSA). We aim to describe the impact of Belatacept use on de novo DSA in lung transplant (LTx).

Methods

A multi-institutional retrospective review of LTx patients with de novo DSA who received Belatacept (January 2018–August 2023) was performed. The primary outcome is the change in DSA post Belatacept initiation. Changes in mean fluorescence intensity (MFI) before and after Belatacept administration were analyzed using a linear mixed-effects model. Secondary outcomes included antibody-mediated rejection (AMR).

Results

Forty-four patients with DSA received Belatacept. Most DSA were class II (n = 41, 93%), with a median (IQR) MFI of 4000 (2500–7000) at Belatacept initiation. Following Belatacept initiation, DSA resolved in (n = 25, 57%) patients, decreased in (n = 7, 16%), and remained unchanged in (n = 12, 27%). No de novo DSA developed during Belatacept therapy. There was no significant change in MFI pre Belatacept administration (change = −38, 95% CI: −267 to 191, p = 0.745), whereas MFI decreased significantly post Belatacept administration (change = −334, 95% CI: −449 to −219, p < 0.001). A total of (n = 25, 57%) patients experienced AMR prior to initiating Belatacept. None of the patients developed AMR while on Belatacept.

Conclusion

This is the largest cohort to date of LTx patients with DSA who received Belatacept. Belatacept use was associated with a reduction in DSA.

背景：Belatacept在肾移植中的应用与相似的移植物存活率和先前存在的供者特异性抗体（DSA）的消除有关。我们的目的是描述使用Belatacept对肺移植（LTx）中新生DSA的影响。方法：对2018年1月至2023年8月期间接受Belatacept治疗的LTx新发DSA患者进行多机构回顾性分析。主要观察结果是belataccept起始后DSA的变化。采用线性混合效应模型分析了给药前后平均荧光强度（MFI）的变化。次要结局包括抗体介导的排斥反应（AMR）。结果：44例DSA患者接受Belatacept治疗。大多数DSA为II级（n = 41, 93%）， belataccept起始时的中位（IQR） MFI为4000（2500-7000）。开始使用Belatacept后，患者的DSA消退（n = 25,57%），下降（n = 7,16%），保持不变（n = 12,27%）。治疗期间无新发DSA。Belatacept给药前MFI无显著变化（变化= -38,95% CI: -267至191，p = 0.745），而Belatacept给药后MFI显著下降（变化= -334,95% CI: -449至-219，p）结论：这是迄今为止接受Belatacept治疗的LTx DSA患者中最大的队列。使用Belatacept可降低DSA。

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引用次数: 0

The Impact of CYP3A4, CYP3A5, and ABCB1 Polymorphisms on Cyclosporine Concentration in Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation CYP3A4、CYP3A5和ABCB1多态性对异基因造血干细胞移植后白血病患者环孢素浓度的影响

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-10 DOI: 10.1111/ctr.70413

Zahra Salehi, Amirhossein Shahsavand, Mohammad Mehdi Naghizadeh, Molouk Hadjibabaie, Shahrbano Rostami, Habibeh Ghadimi, Ahmad Reza Shamshiri, Kamran Alimoghaddam, Fahimeh Rabianataj, Ardeshir Ghavamzadeh, Mohammadreza Ostadali Dehaghi

Cyclosporine A (CsA) is used as graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT). While polymorphisms in CYP3A4, CYP3A5, and ABCB1 genes influence CsA metabolism, their role in HSCT remains underexplored. We investigated the impact of these polymorphisms on CsA pharmacokinetics, early toxicity, and clinical outcomes in 86 leukemia patients undergoing HSCT (IR.TUMS.HORCSCT.REC.1402.07). CsA levels were monitored via radioimmunoassay, and genotyping for CYP3A4, CYP3A5, and ABCB1 polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Carriers of the rs2740574 (CYP3A4*1B, −392A>G) and the rs776746 (CYP3A5*3, 6986A>G) exhibited significantly higher mean trough concentrations compared to the wild-type genotypes (112.6 ± 52.1 versus 75.6 ± 31.0; p = 0.003, 126.1 ± 55.0 versus 89.5 ± 41.8; p < 0.001, respectively). No significant difference was observed for the rs1045642 variants. Both rs776746 and rs2740574 variants were associated with increased markers of nephrotoxicity and hepatotoxicity within 3 days post-HSCT. None of these polymorphisms showed significant associations with transplant outcomes. In conclusion, patients carrying rs776746 or rs2740574 achieved higher CsA trough levels and may require lower initial dosing. Future research should assess whether genotype-guided CsA dosing improves achieving therapeutic levels and reduces early toxicity or suboptimal immunosuppression post-HSCT.

环孢素A （CsA）用于同种异体造血干细胞移植（HSCT）的移植物抗宿主病（GVHD）预防。虽然CYP3A4、CYP3A5和ABCB1基因的多态性影响CsA代谢，但它们在HSCT中的作用仍未得到充分研究。我们研究了这些多态性对86例接受HSCT的白血病患者的CsA药代动力学、早期毒性和临床结果的影响。通过放射免疫法监测CsA水平，并使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对CYP3A4、CYP3A5和ABCB1多态性进行基因分型。rs2740574 （CYP3A4*1B, -392A>G）和rs776746 （CYP3A5* 3,6986a >G）基因型的平均谷浓度显著高于野生型基因型(112.6±52.1 vs 75.6±31.0;p = 0.003, 126.1±55.0 vs 89.5±41.8

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引用次数: 0

Low-Dose Valganciclovir for Primary Cytomegalovirus Prophylaxis After Heart Transplant: A 10-Year Experience 低剂量缬更昔洛韦用于心脏移植后原发性巨细胞病毒预防：10年经验

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation

Pub Date : 2025-12-10 DOI: 10.1111/ctr.70408

Kennedy Concannon, Robert Page, Rebecca Swayngim, Amrut V. Ambardekar, Chia-Yu Chiu, Kelly Schoeppler, Emily Sartain

Background

Due to the hematologic toxicities associated with standard-dose valganciclovir (VGCV), low-dose (LD) VGCV has been proposed as an alternative, primarily in abdominal transplant recipients. Data on LD VGCV outcomes in heart transplant recipients (HTR) remain limited.

Methods

This single-center, retrospective, stimulating cohort study describes adult, cytomegalovirus (CMV) D+/R− and R+ HTR transplanted between January 1, 2013 and September 30, 2022 and maintained on, at most, VGCV 450 mg daily for primary CMV prophylaxis.

Results

A total of 338 HTR were reviewed, of whom 80 CMV D+/R− and 154 R+ HTR met criteria for inclusion. Of the 234 HTR, the median age was 56 years, the mean body mass index (BMI) was 26.9 kg/m², and 93 (39.7%) had an estimated glomerular filtration rate ≥60 mL/min/1.72 m² at post-transplant month 12. Breakthrough (BT) CMV occurred in six (2.6%) individuals, exclusively among CMV D+/R− HTR. Two cases were complicated by CMV end-organ disease (retinitis, colitis) with ganciclovir (GCV) resistance. Leukopenia occurred in 67.1% of the total cohort, necessitating frequent VGCV and mycophenolate adjustments.

Conclusions

This is the largest report of LD VGCV use in HTR. Despite reduced VGCV exposure, HTR remain at high risk for cytopenias. Regardless of potential risk factors, including a high prevalence of overweight BMI and adequate renal function, LD VGCV was associated with expected rates of BT CMV and CMV resistance, suggesting LD VGCV could be considered in HTR. Identification of CMV end-organ disease and GCV resistance suggests that LD VGCV could be considered cautiously in CMV D+/R− HTR.

背景：由于与标准剂量缬更昔洛韦（VGCV）相关的血液学毒性，低剂量（LD） VGCV已被提议作为替代方案，主要用于腹部移植受者。心脏移植受者（HTR）的ldvgcv结局数据仍然有限。方法：这项单中心、回顾性、刺激队列研究描述了2013年1月1日至2022年9月30日期间移植的成人巨细胞病毒（CMV） D+/R-和R+ HTR，并维持每日最多450 mg的VGCV，用于初级CMV预防。结果：共审查了338例HTR，其中80例CMV D+/R-和154例R+ HTR符合纳入标准。在234例HTR中，中位年龄为56岁，平均体重指数（BMI）为26.9 kg/m2，移植后12个月肾小球滤过率≥60 mL/min/1.72 m2的患者有93例（39.7%）。突破性巨细胞病毒（BT）发生在6例（2.6%）个体中，仅发生在CMV D+/R- HTR中。2例合并CMV终末器官疾病（视网膜炎、结肠炎）伴更昔洛韦（GCV）耐药。在整个队列中，有67.1%的患者出现白细胞减少，需要频繁地调整VGCV和霉酚酸盐。结论：这是HTR中最大的ldvgcv使用报告。尽管VGCV暴露减少，HTR仍有发生细胞减少的高风险。不考虑潜在的危险因素，包括BMI超重和肾功能正常的高患病率，LD VGCV与BT CMV和CMV耐药性的预期率相关，提示LD VGCV可在HTR中考虑。CMV终末器官疾病和GCV耐药性的鉴定表明，在CMV D+/R- HTR中，可以谨慎考虑LD VGCV。

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引用次数: 0