JHLT Open最新文献

{"title":"Thrombin generation in HeartMate 3 patients on apixaban and vitamin K antagonists: Variability limits clinical applicability","authors":"Charlotte J. Van Edom MD ,&nbsp;Walter Droogné MD ,&nbsp;Steven Jacobs MD, PhD ,&nbsp;Marc Jacquemin MD PhD ,&nbsp;Christine Van Laer PhD ,&nbsp;Joeri Van Puyvelde MD, PhD ,&nbsp;Dirk Vlasselaers MD, PhD ,&nbsp;Katrien Vandersmissen ,&nbsp;Thomas Vanassche MD, PhD ,&nbsp;Bart Meyns MD, PhD","doi":"10.1016/j.jhlto.2025.100447","DOIUrl":"10.1016/j.jhlto.2025.100447","url":null,"abstract":"<div><div>Apixaban is increasingly replacing vitamin K antagonists (VKAs) during HeartMate 3 (HM3) left ventricular assist device support, but its pharmacodynamics in this setting remain poorly understood. Thrombin generation assays (TGAs) allow for comparison of the overall anticoagulant effect. TGAs were performed in 24 HM3 patients on apixaban, dosed to maintain trough levels &gt;50 ng/liter, and 6 on VKAs with target INR 2 to 3, without recent coagulopathy. Apixaban was associated with shorter lag time and time-to-peak thrombin generation, indicating faster coagulation initiation. Endogenous thrombin potential (ETP) was higher with apixaban, but both peak thrombin and ETP showed high interindividual variability. Apixaban levels correlated modestly with initiation parameters, but not with ETP or peak thrombin. These findings demonstrate pharmacodynamic differences between apixaban and VKAs, but also highlight substantial variability and limited clinical applicability for apixaban dose titration. TGAs should therefore be regarded as research tools rather than monitoring assays in this setting.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100447"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival improvement with sirolimus plus tacrolimus immunosuppression for treatment of bronchiolitis obliterans syndrome after lung transplantation","authors":"Marniker Wijesinha PhD ,&nbsp;Michael Terrin MD ,&nbsp;Si Pham MD ,&nbsp;Aldo Iacono MD","doi":"10.1016/j.jhlto.2025.100469","DOIUrl":"10.1016/j.jhlto.2025.100469","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rejection, usually manifesting as bronchiolitis obliterans syndrome (BOS), is the leading cause of death among lung transplant patients. Prior lung transplant studies showed higher overall survival and lower BOS incidence associated with sirolimus (SIR) + tacrolimus (TAC) versus conventional mycophenolate mofetil (MMF) + TAC immunosuppression. However, after BOS occurs, it is unknown how immunosuppressive drugs may be linked to survival.</div></div><div><h3>Methods</h3><div>This study included U.S. lung transplant recipients in the Lung Allocation Score era (starting May 2005), with a BOS diagnosis documented from 2006 to 2020, in the Scientific Registry of Transplant Recipients dataset. Survival was compared between patients receiving MMF+TAC, SIR+TAC, or SIR+TAC+MMF/azathioprine (SIR+TAC+MMF/AZA) after BOS onset, using multivariable adjusted Cox regression and Inverse Probability of Treatment Weighting (IPTW)-adjusted Kaplan-Meier estimates.</div></div><div><h3>Results</h3><div>SIR+TAC+MMF/AZA (HR=0.60, p=0.03, n=47) and SIR+TAC (HR=0.67, p=0.04, n=95) were associated with better survival than MMF+TAC (n=1012); each group contained patients from &gt;15 centers. IPTW-adjusted survival probabilities for SIR+TAC+MMF/AZA, SIR+TAC, and MMF+TAC, respectively, were, 1-year: 91%, 84%, 80% and 5-year: 50%, 58%, 42%. Within severely affected BOS patients (BOS Grade 3, or FEV₁ decrease ≥30%/year, or FEV₁&lt;25% of predicted at BOS documentation), SIR+TAC+MMF/AZA (HR=0.32, p=0.03) and SIR+TAC (HR=0.50, p=0.05) had larger survival advantages over MMF+TAC; the respective survival probabilities were, 1-year: 91%, 70%, 59%, and 5-year: 41%, 35%, 20%.</div></div><div><h3>Conclusions</h3><div>Sirolimus + tacrolimus immunosuppression may improve survival in BOS patients, especially severely affected patients with BOS Grade 3, or rapidly declining or low FEV₁. Adding MMF or azathioprine to this combination may further increase short-term survival.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100469"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Listing patterns at the highest volume heart transplant centers: Multiple roads to transplant","authors":"Joshua A. Rushakoff MD, MPP ,&nbsp;Adam D. DeVore MD, MHS ,&nbsp;Richa Agarwal MD ,&nbsp;Joseph B. Lerman MD ,&nbsp;Karen Flores Rosario MD ,&nbsp;Jeffrey Keenan MD ,&nbsp;Jacob N. Schroder MD ,&nbsp;Carmelo A. Milano MD ,&nbsp;Chetan B. Patel MD","doi":"10.1016/j.jhlto.2025.100479","DOIUrl":"10.1016/j.jhlto.2025.100479","url":null,"abstract":"<div><div>The current heart transplantation (HT) allocation system added additional progressive statuses to differentiate the highest risk patients and decrease waitlist mortality. We analyzed United Network for Organ Sharing thoracic organ data (10/18/2018-6/30/2025) to assess listing practices at the 10 highest volume centers (5,466 total HT). We found variation in the final waitlist status across these centers (status 1 3.6% to 16.4%; status 6 0.5%-14.5%). Further, some centers had more even distributions across final status, while others had dominant status 2 patterns. As continuous distribution allocation is considered for HT, we feel it is critical to consider the practice patterns of these highest-volume centers. Notably, HT candidates may not conform to a prescribed course through escalating statuses.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100479"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaposi sarcoma in lung transplant recipients with public health service increased-risk donors: A retrospective cohort study and review of the literature","authors":"Shoaib Ahmad MD ,&nbsp;Curt Bay PhD ,&nbsp;Michael D. Nailor PharmD ,&nbsp;Christine Pham PharmD ,&nbsp;Ross M. Bremner MD, PhD ,&nbsp;Ali Imran Saeed MD ,&nbsp;Kellie J. Goodlet PharmD ,&nbsp;Sofya Tokman MD","doi":"10.1016/j.jhlto.2025.100468","DOIUrl":"10.1016/j.jhlto.2025.100468","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the relationship between Public Health Service (PHS) increased-risk donors and post-lung transplant (LT) Kaposi sarcoma (KS).</div></div><div><h3>Methods</h3><div>This retrospective cohort study included LT recipients (April 1, 2019-April 1, 2024) who had PHS increased-risk donors at our institution. Data were abstracted from UNOS and electronic medical records. Published post-LT KS cases were also reviewed. Descriptive statistics and Kaplan–Meier estimates were used.</div></div><div><h3>Results</h3><div>Of 467 LT recipients, 90 (23.9%) had PHS increased-risk donors, including 13 [14.4%] men who have sex with men (MSM). Four of these 13 (30.8%) recipients developed KS (median time to diagnosis, 365 days [IQR 276–502]). Basiliximab was the most common induction agent; all 4 patients were on standard 3-drug immunosuppression. All 4 recipients had pulmonary KS without extrapulmonary involvement and positive human herpes virus 8 (HHV-8) immunohistochemistry results. Pulmonary nodules were incidentally noted on chest CT in 3 asymptomatic patients; 1 patient presented with dyspnea and central airway obstruction. Immunosuppression was reduced and mTOR inhibitors were initiated for all 4 patients; 1 patient underwent stenting of the left main bronchus and radiation, and 1 was treated with liposomal doxorubicin. Three recipients improved, and 1 is awaiting follow-up imaging (median follow-up, 276 days [IQR 177–433]). In our data pooled with 15 published cases, mean survival time was lower in patients with disseminated KS (182 vs. 563 days, p=0.011).</div></div><div><h3>Conclusion</h3><div>LT recipients with MSM donors may be at an increased risk for post-LT KS from donor-derived HHV-8. Larger, more definitive, multicenter studies are needed.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100468"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Veno-venous versus Veno-arterial extracorporeal membrane oxygenation for the management of primary graft dysfunction following lung transplantation: A systematic review and meta-analysis","authors":"Erlon de Avila Carvalho MD, PhD ,&nbsp;Bruna Carregal Coelho MSc ,&nbsp;Rachid Eduardo Noleto da Nobrega Oliveira MD, MS ,&nbsp;Lucas Monteiro Delgado MSc ,&nbsp;Felipe S. Passos MD ,&nbsp;Tulio Caldonazo MD ,&nbsp;Marcelo Cypel MD, PhD","doi":"10.1016/j.jhlto.2025.100437","DOIUrl":"10.1016/j.jhlto.2025.100437","url":null,"abstract":"<div><h3>Background</h3><div>Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. In its severe forms, extracorporeal membrane oxygenation (ECMO) may be required. However, there is no consensus on whether venovenous (VV) or venoarterial (VA) ECMO modality provides superior outcomes. The objective of this meta-analysis is to compare the use of VV-ECMO versus VA-ECMO in the management of grade 3 PGD after lung transplantation.</div></div><div><h3>Methods</h3><div>Three databases were assessed. Primary outcome was overall survival (OS). Secondary outcomes included cerebrovascular complications, incidence of pneumonia, reintubation, acute kidney injury, ICU length of stay and ECMO duration. Hazard ratios (HR), odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated. Reconstruction of time-to-event data and sensitivity analyses were performed for the primary endpoint.</div></div><div><h3>Results</h3><div>Four studies including 210 patients (VV-ECMO: 142; VA-ECMO: 68) were analyzed. VV-ECMO was associated with improved early survival (HR 0.41; 95%CI 0.22 to 0.76; p=0.005) within the first 2 months after transplantation, although no significant difference was observed in long-term survival (HR 0.72; 95%CI 0.46 to 1.15; p=0.168). Cerebrovascular complications occurred significantly more often in the VA-ECMO group (OR 18.33; 95%CI 3.62 to 92.81; p=0.0004), while no significant differences were found in pneumonia, reintubation, acute renal failure, ICU length of stay, or ECMO duration.</div></div><div><h3>Conclusion</h3><div>VV-ECMO appears to be associated with better short-term survival and fewer neurological complications compared to VA-ECMO in patients with grade 3 PGD after lung transplantation.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100437"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venous thromboembolism in lung transplant recipients: timing and clinical impact, a 10-year cohort analysis","authors":"Dieuwertje Ruigrok MD, PhD ,&nbsp;Lucie E. Boersma MD ,&nbsp;Jon Admiraal MD ,&nbsp;Ares M. Rasoul MD ,&nbsp;Nuray Kusadasi MD, PhD ,&nbsp;Sue A. Braithwaite MD ,&nbsp;Linda M. de Heer MD, PhD ,&nbsp;Bart Luijk MD, PhD ,&nbsp;Rob Schönwetter MD ,&nbsp;Marco C. Post MD, PhD","doi":"10.1016/j.jhlto.2025.100458","DOIUrl":"10.1016/j.jhlto.2025.100458","url":null,"abstract":"<div><h3>Introduction</h3><div>The burden of venous thromboembolism (VTE) in lung transplant (LTx) recipients is not fully elucidated despite its frequent occurrence. We report the incidence of VTE and characteristics of VTE in a large LTx cohort, assess severity using risk stratification algorithms, and explore associations with graft survival and chronic lung allograft dysfunction (CLAD).</div></div><div><h3>Methods</h3><div>A retrospective cohort analysis was performed on LTx recipients transplanted between July 2012 and August 2022 in our center. Primary outcome was incidence of VTE. Three groups were compared as follows: patients with early VTE (i.e<em>.,</em> within the first 6 months after LTx), late VTE (i.e<em>.,</em> beyond the first 6 months after LTx), and no VTE.</div></div><div><h3>Results</h3><div>About 94/286 patients (33%) were diagnosed with VTE (median follow-up of 4.3 years): 67/94 (71%) early VTE and 27/94 (29%) late VTE. 66/94 (70%) of VTE events were pulmonary embolism (PE). In the early VTE group, none of the PE cases were classified as intermediate-high risk PE and 1 patient had high-risk (fatal) PE. Graft survival was not different between groups; median CLAD-free survival was shorter in patients with late VTE (6.2 years) compared to patients without VTE during follow-up (9.8 years) (<em>p</em> = 0.044).</div></div><div><h3>Conclusions</h3><div>Thirty-three percent of LTx recipients developed VTE, 71% within the first 6 months after LTx. Seventy percent of cases were acute PE, but fatal or severe nonfatal PE were rare. No effect of VTE on graft survival was seen; CLAD-free survival was shorter in patients with late VTE compared to patients without VTE.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100458"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of severe obesity on heart transplantation outcomes: A meta-analysis of survival and complications","authors":"Ana Maria Bicudo Diniz MD ,&nbsp;Adriana Loricchio Veiga MD ,&nbsp;Sofia Wagemaker Viana ,&nbsp;Anaís Concepcion Marinho Andrade de Moura MD ,&nbsp;Beatriz Laus P. Lima ,&nbsp;Niti Dalal MBBS MD ,&nbsp;Aabha Divya MBBS, MCh","doi":"10.1016/j.jhlto.2025.100404","DOIUrl":"10.1016/j.jhlto.2025.100404","url":null,"abstract":"<div><h3>Background</h3><div>Heart transplantation (HT) is the standard treatment for end-stage heart failure, but severe obesity (Body Mass Index [BMI] ≥ 35 kg/m²) is linked to worse outcomes and is considered a relative contraindication. Obese patients face increased perioperative risks, longer wait times, and reduced survival, though improved clinical care may mitigate some effects. As obesity rates rise, the suitability of the current BMI is increasingly debated. Evidence remains limited and inconsistent, highlighting a need for clearer guidance. This systematic review and meta-analysis assess the impact of severe obesity on survival and post-transplant complications in HT recipients.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and was registered in PROSPERO (CRD420251036442). We included cohort studies and randomized controlled trials (RCTs) (2000–2025) comparing outcomes in adult heart transplant recipients with a BMI ≥ 35 kg/m² vs lower BMI. Primary outcomes were mortality and post-transplant complications. Searches were conducted in PubMed, Scopus, Embase, and Cochrane CENTRAL. Multiple reviewers did data extraction and bias assessment (ROBINS-I) independently. Random-effects models were used for statistical analysis, with heterogeneity assessed via I², and sensitivity analyses performed. Publication bias was evaluated using funnel plots.</div></div><div><h3>Results</h3><div>The search strategy retrieved 1,697 articles or abstracts, 595 were excluded for being duplicates, and 59 full-text articles were selected for full-text analysis. Of these, 9 cohorts were included, 7 from the United States and 2 from Canada, with 218,272 patients, of whom 206,459 had a BMI &lt; 35 and 11,813 had a BMI ≥ 35kg/m².</div></div><div><h3>Conclusion</h3><div>This meta-analysis shows that severe obesity (BMI ≥ 35 kg/m²) remains associated with higher rates of infection, graft failure, and post-transplant mortality, despite advances in care. These outcomes likely reflect underlying immune and metabolic dysfunctions in obese patients, emphasizing the need for tailored strategies to improve long-term survival after heart transplantation.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100404"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathologists’ experience and routine practice in high-volume lung transplant centers: An international survey","authors":"Fiorella Calabrese MD ,&nbsp;David M. Hwang MD ,&nbsp;Francesca Lunardi MD, ScD, PhD ,&nbsp;Riccardo Iannaco MPharm ,&nbsp;Julien Adam MD ,&nbsp;Levent M. Akyürek MD ,&nbsp;Benjamin Adam MD ,&nbsp;Balko Jan MD, PhD ,&nbsp;Gerald Berry MD ,&nbsp;Lauren D’Sa MD ,&nbsp;Aurelie Fabre MD ,&nbsp;Antonin Fattori MD ,&nbsp;Gregory A. Fishbein MD ,&nbsp;Kristianna M. Fredenburg MD, PhD ,&nbsp;Teresa Hermida Romero MD ,&nbsp;Aliya N. Husain MD ,&nbsp;Kirk Jones MD ,&nbsp;Izidor Kern MD ,&nbsp;Chieh-Yu Lin MD ,&nbsp;Rita Louis MD ,&nbsp;Deborah J. Levine MD","doi":"10.1016/j.jhlto.2025.100415","DOIUrl":"10.1016/j.jhlto.2025.100415","url":null,"abstract":"<div><div>Lung allograft pathology encompasses a wide spectrum of disorders, with new entities and emerging diagnostic technologies. The main goal of this study was to document pathologists’ current global practices and highlight areas of consensus and divergence worldwide. A 24-item survey was distributed to transplant centers and responses were received from 35 specialists (51% European, 49% non-European). Most centers used both surveillance and symptom-driven assessments (77%), mainly with transbronchial biopsies (86%) and bronchoalveolar lavage (83%). Non-European centers were more likely to adopt digital pathology (OR 3.03), to use donor-derived cell-free DNA (dd-cfDNA) (OR 2.94), and supported large airway sampling (OR 2.27). Larger centers used dd-cfDNA (OR 2.75) more frequently and consider large airway sampling (OR 2.18). Responders largely supported standardized reporting (86%), reintroducing grade AX (94%), and independent bronchial lesion scoring (82%). Most endorsed an “indeterminate” category for acute and chronic rejection. These findings reflect evolving practices in the field and will inform the ongoing revision of the Lung Allograft Pathology Working Classification.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100415"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limitations of ventricular assist devices in pediatrics: When one size does not fit all","authors":"Áine Lynch ,&nbsp;Aamir Jeewa","doi":"10.1016/j.jhlto.2025.100428","DOIUrl":"10.1016/j.jhlto.2025.100428","url":null,"abstract":"<div><div>Ventricular assist device (VAD) use in pediatric heart failure is an evolving field with increasing volume and case complexity of patients supported. Despite this, limited VADs used are developed for infants and children, with significant numbers supported using adult devices. While outcomes on support are influenced by a variety of factors, including illness severity at VAD implant, need for additional right heart support, and presence of congenital heart disease, body size remains an independent predictor of mortality and adverse events on VAD support. Those patients able to accommodate adult-designed implantable continuous-flow VADs experience markedly improved survival outcomes and lower complication rates with improved rehabilitation potential. For the remaining cohort, device choices are limited to extracorporeal VAD support with inferior outcomes and care limited to hospital settings. The deficit in pediatric-specific VAD devices is a well-recognized need to optimize care for this complex cohort.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100428"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary approach to desensitization: Targeted therapies for HLA sensitized pediatric heart transplant candidates – Study design and rationale","authors":"Lakshmi R. Gokanapudy Hahn MD, MSCI ,&nbsp;Marlena Habal ,&nbsp;Adriana Zeevi ,&nbsp;Kathleen E. Simpson ,&nbsp;Warren Zuckermann ,&nbsp;Kevin Daly ,&nbsp;Chad Mao ,&nbsp;Joseph Rossano ,&nbsp;James K. Kirkin ,&nbsp;Charles E. Canter","doi":"10.1016/j.jhlto.2025.100429","DOIUrl":"10.1016/j.jhlto.2025.100429","url":null,"abstract":"<div><h3>Purpose</h3><div>HLA sensitization significantly limits donor availability and increases waitlist mortality in pediatric heart transplantation (HT). Current desensitization strategies are largely ineffective or equivocal. Recent adult studies show that a dual approach with Carfilzomib (CFZ), a proteasome inhibitor, and Belatacept (BELA), a costimulation blocker, reduces class I and II HLA antibodies (Abs). This study will evaluate the clinical utility of CFZ and BELA in reducing HLA antibody type and strength in pediatric and young adult patients.</div></div><div><h3>Methods</h3><div>This prospective, observational study will include about 30 patients from 6 pediatric clinical sites, an HLA core and a mechanistic core lab. Patients aged 10–24 years, highly sensitized with class I and/or class II cPRA ≥ 50% (MFI &gt; 4000), will be included. Exclusion criteria: EBV seronegative, HIV+, and a history of hematologic malignancy. Secondary endpoints include mechanistic studies on how desensitization affects cellular subsets producing HLA Abs, whether reductions in antibody strength persist until transplant, and post-transplant outcomes such as antibody mediated rejection and graft survival.</div></div><div><h3>Results</h3><div>The study’s unique design harmonizes the use of a novel protocol across sites using a central IRB and is the first prospective, registry-based investigation in pediatric HT using the Pediatric Heart Transplant Society (PHTS) registry. The HLA core will measure antibody response through MFIs, titers, and cPRA, while the mechanistic core will use advanced investigations to support the trial's clinical endpoints.</div></div><div><h3>Conclusion</h3><div>This multicenter study aims to establish a transformative, standardized approach to desensitization and antibody evaluation.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100429"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}