BACKGROUND:ABO antigens are broadly expressed on endothelial and epithelial glycoproteins and modulate innate immune responses, complement activation, tissue immunogenicity, and endothelial-derived haemostatic factors. Their differential distribution across the specific diagnoses that lead to end-stage organ failure has been little explored in Latin American populations, where a high prevalence of group O provides a distinct genetic background to examine these associations. We report an exploratory analysis in national transplant waiting list of Ecuador. METHODS:We conducted a retrospective study of 4408 patients on Ecuador's national transplant waiting list (2017-2022) who had a known ABO group. The sample included kidney (n = 2326), cornea (n = 1733), liver (n = 323), heart (n = 22), and lung (n = 4) transplant candidates. We tested associations using Fisher's exact test (simulated p-values with 5000 replicates), Cramér's V with bootstrap 95% CI, binary logistic regression (O vs. nonO), and a goodness-of-fit test against Ecuadorian population frequencies. We corrected for multiple testing with the Benjamini-Hochberg method. RESULTS:Three ABO associations remained significant after correction: ABO with corneal diagnosis (p_BH = 0.007; V = 0.110), ABO with organ type (p_BH = 0.004; V = 0.059), and ABO with age at waitlist entry (p_BH = 0.014; V = 0.061). Residual analysis showed that groups A and AB were more frequent than expected among patients with type 2 diabetes as the cause of end-stage renal disease (r = +2.80 and +3.18), while group O was less common (r = -2.66). In corneal patients, group A was underrepresented in adherent leukoma (r = -2.26) and vesicular keratopathy (r = -2.04). Liver disease showed no ABO signal (p = 0.996). No Rh-related association survived multiple-testing correction, supporting the specificity of the ABO signal. CONCLUSIONS:The ABO blood group appears to have an uncharacterized, organ-specific effect on end-stage organ and corneal failure. In our analysis of transplant candidates, the corneal association survived multiple-testing correction and remained robust in the sensitivity analysis for missing ABO data. Groups A and AB were enriched among patients with type 2 diabetes as a cause of end-stage renal disease, and group A was underrepresented in adherent leukoma and vesicular keratopathy. No association was detected in hepatic disease, and no Rh-related association was significant after correction.
BACKGROUND:Chronic lung allograft dysfunction (CLAD) is a major cause of post-lung transplant mortality, with limited medical treatment options. This exploratory single-center real-world retrospective study aimed to evaluate the clinical outcomes and safety of belumosudil in lung transplant recipients with the bronchiolitis obliterans syndrome (BOS) phenotype of CLAD. METHODS:An exploratory single-center real-world retrospective study was conducted of lung transplant recipients with CLAD-BOS who received belumosudil for at least 3 months between September 2024 and November 2025. Primary endpoint was treatment response to belumosudil as classified based on changes in forced expiratory volume in 1 s (FEV1). RESULTS:A total of 17 CLAD-BOS patients were included (9 CLAD stage 1-2 patients and 8 CLAD stage 3-4 patients). Treatment response to belumosudil was assessed at 3, 6, and 12 months after initiating belumosudil. At 3 months, 17.6% of patients achieved a response, 64.7% remained stable, and 17.6% were non-responders. At 6 and 12 months, most patients showed stabilization or improvement in FEV1 (6 months: 68.8%, 11/16; 12 months: 70%, 7/10), while a minority exhibited a continued decline. All CLAD stage 1-2 patients achieved response or stabilization at 3 months, while no responses were observed in CLAD stage 3-4 patients. This stage-dependent pattern persisted at 6 and 12 months. Mixed-model analyses confirmed more favorable changes in FEV1 and forced vital capacity (FVC) in early-stage patients. No significant adverse events were observed. CONCLUSIONS:This exploratory single-center real-world study provides preliminary hypothesis-generating evidence that belumosudil may be associated with stabilization of pulmonary function in lung transplant recipients with CLAD-BOS, particularly when initiated during earlier disease stages. These findings require confirmation in larger prospective controlled studies.
BACKGROUND:Lung transplantation is a recognized treatment for children with end-stage lung disease that can prolong their life and improve their quality of life. Currently, there are few reports on the clinical efficacy of lung transplantation in children. METHODS:We retrospectively analyzed the clinical data of children who underwent lung transplantation at the Affiliated Wuxi People's Hospital of Nanjing Medical University between 2019 and 2022. The follow-up deadline was November 2023. RESULTS:Between 2019 and 2022, 13 pediatric patients underwent lung transplantation at our center. None of the patients tolerated the pulmonary function test and the 6-min walking test before surgery. All patients underwent double lung transplantation, and four patients underwent lung volume reduction prior to chest closure. All patients survived for more than 30 days except one patient who died 4 days after surgery. The forced expiratory volume in one second and the forced vital capacity after surgery were 84 ± 18% and 84 ± 11% of the predicted values, respectively. The result of the six-minute walking test was 417 ± 26 m. CONCLUSION:Pediatric lung transplantation is a feasible treatment option for children with end-stage lung disease that can extend their life and improve their quality of life.
BACKGROUND:Post-transplant cyclophosphamide (PTCy) is central to graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT); however, there remains an opportunity for further advancement. OBJECTIVE:This study aimed to evaluate the efficacy of dual T-cell depletion using low-dose PTCy and antithymocyte globulin (ATG) for GVHD prophylaxis in peripheral blood allo-HCT. METHODS:Patients with acute leukemia or myelodysplastic syndrome (MDS) who received either PTCy or ATG/PTCy for GVHD prophylaxis were included. Transplant outcomes were compared between the PTCy and ATG/PTCy groups. In the ATG/PTCy group, rabbit ATG (3.0-4.0 mg/kg according to recipient absolute lymphocyte count) and dose-attenuated PTCy (50 mg/kg on day +3 and 30 mg/kg on day +4) were administered. RESULTS:A total of 97 patients were included. Neutrophil engraftment was faster in the ATG/PTCy group. There were no significant differences between the two groups in overall survival, relapse-free survival, or GVHD-free, relapse-free survival. The cumulative incidences of relapse, non-relapse mortality, and grade III-IV acute GVHD were comparable between the two groups. In contrast, the ATG/PTCy group showed a lower incidence of moderate-severe chronic GVHD (2-year: 3.7% [95% CI, 0.7%-11.4%] vs. 17.0% [95% CI, 7.3%-30.2%], P = 0.046). On multivariate analysis, ATG/PTCy was independently associated with a lower risk of moderate-severe cGVHD, but not with relapse, non-relapse mortality, or survival outcomes. CONCLUSION:The addition of low-dose ATG to PTCy may further reduce moderate-severe chronic GVHD compared with PTCy alone, without increasing the risk of relapse or NRM, resulting in improved GRFS.
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for relapsed or refractory classical Hodgkin lymphoma (cHL); however, a substantial subset of patients ultimately requires allogeneic hematopoietic stem cell transplantation (allo-HCT) to achieve long-lasting disease control. The use of ICIs as a bridge to allo-HCT has therefore gained increasing clinical interest, though concerns persist regarding post-transplant complications and incompletely-defined safety profiles. Accordingly, this systematic review and meta-analysis was conducted to evaluate outcomes of ICIs administered prior to allo-HCT in cHL. Following PRISMA guidelines, a comprehensive literature search was conducted across online databases through January 2026. Eligible studies included observational designs reporting survival and transplant-related outcomes in cHL patients treated with ICIs followed by allo-HCT. Pooled proportions for overall survival, progression-free survival, non-relapse mortality, and graft-versus-host disease (GVHD) incidence were calculated using a random-effects model. Seven studies comprising 739 patients were included. Post-transplant survival outcomes were favorable, with high pooled estimates across timepoints. Transplant-related mortality remained low, with NRM rates consistently within an acceptable range through long-term follow-up. Acute GVHD was observed at a meaningful frequency, including a smaller subset of severe cases, while chronic GVHD occurred in approximately one-quarter of patients at follow-up. Overall, these findings suggest that ICI therapy prior to allo-HCT in cHL is associated with encouraging survival and disease control and does not appear to confer excessive non-relapse mortality, supporting its use as a feasible and effective bridging strategy, while underscoring the need for future prospective studies to clarify optimal timing, risk mitigation strategies, and patient selection.
Background Vascularized composite allotransplantation (VCA) offers life changing reconstructive options for patients with traumatic injuries or congenital defects, restoring function and appearance. Its success is limited by strong immune responses, and long-term immunosuppression carries significant risks. Emerging cellular therapies, particularly regulatory T cells (Tregs) offer promising strategies to mitigate rejection and reduce immunosuppression dependence. Preclinical studies in animal models suggest that Treg-based approaches may improve graft survival and potentially reduce the need for conventional immunosuppression in VCA. Methods An all-time literature search of Regulatory T cell therapy in Vascularized Composite Allotransplantation in animal models was performed on the following electronic databases: PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and TRIP Database until August 2025. Data was analyzed for graft survival, regulatory T cell activity, chimerism, and tolerance mechanisms. Results A total of 2182 studies were screened across six databases, of which 13 met eligibility criteria and 5 were selected focusing on Treg therapy in VCA animal models. Treg therapy consistently prolonged graft survival (>200 days), promoted chimerism, reduced inflammation, and induced donor specific tolerance. CAR-Tregs demonstrated antigen-specific tolerance, while mesenchymal stem cells (MSCs) enhanced immunomodulation, particularly under hypoxic preconditioning. Other cellular therapies, including hematopoietic stem cells (HSC), also improved graft acceptance, demonstrating their potential as adjuncts or alternatives to long term immunosuppression. Conclusion Cellular therapies, especially Treg based approaches such as adoptive transfer and local enrichment or induction of Tregs, consistently promote immune tolerance, suppress graft rejection, and extend allograft survival in VCA animal models. These approaches reduce the need for long term immunosuppression and create a pro-tolerogenic environment, supporting their translational potential. However, further clinical validation is required to optimize dosing, persistence and safety for application in human VCA recipients.
BACKGROUND:Epstein-Barr virus (EBV) infection or reactivation is an emerging but underrecognized complication following chimeric antigen receptor T-cell (CAR-T) therapy and is likely associated with treatment-induced immune dysregulation. Data regarding its clinical impact remain limited. OBJECTIVE:To evaluate the reported occurrence, clinical manifestations, and outcomes of EBV infection or reactivation in adults undergoing CAR-T therapy. METHODS:A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, and Cochrane CENTRAL were searched from inception to March 2025 for studies reporting EBV infection or reactivation after CAR-T therapy in adults. Due to limited and heterogeneous data, results were synthesized descriptively. RESULTS:Five studies comprising 80 patients were included (median age, 55 years; 52.6% male among patients with reported sex data [10/19]). Across the included studies, 11 EBV infection/reactivation events were identified among 80 described CAR-T recipients, representing 13.8% of the reported sample rather than a true incidence estimate. Among events with usable individualized timing data, the median interval from CAR-T infusion to EBV detection/reactivation was 9.8 months (approximate range, 1-44 months). Because EBV surveillance strategies and definitions were inconsistently reported across studies, this proportion should not be interpreted as a true incidence estimate. Four patients (36.4%) developed EBV-associated disease, including three cases of EBV-related lymphoproliferative disorder and one case of EBV-associated diffuse large B-cell lymphoma. Among seven patients with reported post-CAR-T treatment response, four achieved Complete Remission/ Continuous Complete Remission; treatment response should be interpreted separately from final survival status. Confirmed EBV-related mortality occurred in 2/11 patients with reported EBV infection/reactivation and in 2/4 patients with EBV-associated disease; all-cause mortality could not be reliably estimated because patient-level vital status could not be fully attributed to the EBV-reactivated subgroup. Reported toxicities predominantly consisted of low-grade cytokine-release syndrome; however, toxicity data were limited. CONCLUSION:Although infrequently reported, EBV infection or reactivation after CAR-T therapy may be associated with substantial morbidity and mortality among affected patients. However, the available evidence is limited by the small sample size, heterogeneous study designs, and inconsistent EBV surveillance practices.
Antibody-mediated rejection (ABMR) remains a leading cause of renal allograft failure, characterized by peritubular capillaritis and endothelial inflammation. M1-polarized macrophages are abundantly recruited to allograft tissues during ABMR. However, the role of their secreted exosomes in vascular injury remains insufficiently defined. Here, we demonstrate that exosomes derived from M1 macrophages (M1-Exos) potently induce endothelial activation and inflammatory injury. Through transcriptomic and exosomal proteomic analyses, spleen tyrosine kinase (Syk) was identified as a protein significantly enriched in M1-Exos. Functional assays showed that M1-Exos promote the upregulation of ICAM-1, VCAM-1, and inflammatory cytokines in endothelial cells, while genetic knockdown of Syk in M1 macrophage reduced these effects. Mechanistically, exosomal Syk is transferred to endothelial cells and associates with NLRP3, driving inflammasome activation and caspase-1 cleavage. In a murine model of renal transplant, Syk-enriched exosomes aggravated endothelial injury. Meanwhile, Syk-deficient exosomes attenuated endothelial inflammation signs of ABMR in grafts. These findings identify exosomal Syk as a novel mediator of endothelial inflammation and provide insights into macrophage-endothelium communication in the setting of allograft rejection.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose by promoting urinary glucose excretion and also exert anti-inflammatory and organ-protective effects. This study examined the effects of short-term peri-operative SGLT2 inhibition with ipragliflozin on islet transplantation in a mouse model of diabetes. Streptozotocin-induced diabetic mice underwent portal vein islet transplantation and received either ipragliflozin (Tx + Ip, n = 16) or no treatment (Tx, n = 16) during the perioperative period. At 4 weeks after transplantation, outcomes assessed included blood glucose normalization, body weight, glucose tolerance, insulin secretion, and hepatic expression of inflammatory markers and islet-specific genes. The Tx + Ip group showed a higher rate of blood glucose normalization (75% vs. 25%, p < 0.05), improved glucose tolerance, and higher fasting insulin levels compared with the Tx group. Early hepatic expression of inflammatory markers (tumor growth factor-β, interferon-γ, and interleukin-6) was lower in the Tx + Ip group, whereas expression of the islet survival gene Pdx1 was higher on day 5, suggesting enhanced islet engraftment. These findings indicate that short-term perioperative ipragliflozin improves islet transplantation outcomes in diabetic mice by attenuating early inflammation and supporting islet survival and function, with potential translational relevance for clinical islet transplantation strategies.
OBJECTIVE:The aim of this study was to evaluate the efficacy and safety of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL), focusing on immune interventions' impact on long-term prognosis. METHODS:16 adult patients (≥18 years; 11 male, 5 female; median age 28 years [range 18-50]) with R/R T-ALL/LBL undergoing salvage allo-PBSCT at the Chinese PLA General Hospital between 2013 and 2022 were retrospectively analyzed. All patients were in partial remission (PR) or disease progression (PD) pre-transplant. Primary endpoints were overall survival (OS), progression-free survival (PFS), and relapse rate (RR); secondary endpoints included GVHD incidence and immune intervention efficacy. Median follow-up was 15.5 months (range 2-69). RESULTS:5 patients (31.3%) survived at last follow-up. At 3-month post-transplantation assessment, 9 patients achieved CR and 5 maintained PR, while 2 patients died of PD within 2 months post-transplant. Among the 14 evaluable patients, CR patients (n = 9) received immunosuppressant tapering without additional intervention: 4 sustained CR, 2 died of relapse, 3 of transplant-related mortality. PR patients (n = 5) underwent initial immunosuppression withdrawal followed by: donor lymphocyte infusions (DLI, n = 3), chemotherapy (n = 1), or DLI + radiotherapy (n = 1). 4 patients ultimately died of relapse, and 1 attained CR. The 1-year OS and PFS were both 56.3%, 1-year RR was 22.1%, and non-relapse mortality rate (NRM) was 27.1%. CONCLUSION:Myeloablative allo-PBSCT is a feasible salvage therapeutic option for R/R T-ALL/LBL patients. Furthermore, immune interventions, such as DLI, may improve outcomes, particularly in patients with PR.
Human Leucocyte Antigen (HLA) sensitisation following red cell transfusion can disrupt planned transplantation and impair outcomes. We conducted a prospective, randomised controlled, double blinded, parallel arm study to evaluate the efficacy of HLA selected red cell transfusions in preventing blood donor specific HLA antibodies (bDSA). Participants were recruited to two groups: adults requiring transfusion or surgery, and paediatric cardiac surgery patients; and randomised to receive red cells selected for HLA compatibility from HLA-typed blood donors, or unselected red cells. Exclusion criteria included recent transfusions, immunoglobulin or B cell depleting treatments, and requirement for additional blood products. The primary outcome was cumulative incidence of de novo bDSA, by HLA antibody testing pre- and post-transfusion. 73 adult participants and 68 paediatric participants were randomised, with 26 and 52 respectively completing the study. Many randomised participants (40% and 59% in adult and paediatric groups respectively) received non-trial products, and there was no significant difference between treatment groups in the intention-to-treat analyses. No de novo bDSA were detected in participants who had received trial products only, while de novo bDSA were detected in participants who received unselected red cell products. Larger studies could confirm the potential to avoid HLA sensitisation by blood donor selection.
OBJECTIVE:Hemophagocytic lymphohistiocytosis (HLH) is an immune dysregulation syndrome with an extremely poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative treatment for high-risk HLH. This study aimed to evaluate the efficacy, safety, prognostic factors, and bridging value of novel targeted therapies in adolescent and adult patients with HLH. METHODS:We retrospectively analyzed the clinical data of 35 adolescents and adults with HLH who underwent individualized myeloablative conditioning (MAC)-based allo-HSCT between April 2019 and November 2025. RESULTS:Sustained hematopoietic engraftment was achieved in 34 of 35 patients (97.1%). With a median follow-up of 17 months, the estimated 1- and 2-year overall survival (OS) rates were 78.2% and 74.1%, respectively, and the 1- and 2-year relapse-free survival (RFS) rates were 73.0% and 69.0%, respectively. Notably, patients in an inactive disease state (complete or partial remission) prior to transplantation demonstrated a significantly superior 1-year RFS rate compared with those in an active state (86.3% vs. 48.6%, P = 0.022). Furthermore, Cox regression analysis identified elevated pre-transplant serum creatinine as a significant adverse prognostic factor for OS (HR = 1.02, P = 0.004). CONCLUSION:Allo-HSCT achieved high engraftment rates and acceptable a safety profile across different HLH subtypes. Achieving at least partial remission (in an inactive state) before transplantation significantly improves survival. For critically ill patients with an extremely high inflammatory burden, emapalumab serves as an effective salvage strategy for bridging transplantation. Furthermore, the cellular tracing of EBV-R using advanced sorting technologies is of great clinical value for differentiating simple viremia from early tumor relapse.
