Antimicrobial management in pediatric transplantation lacks standardized international guidelines, and current practices across European transplant centers remain poorly described. This study aimed to evaluate microbiological screening and peri-transplant antimicrobial strategies among centers participating in the European Reference Network on Transplantation in Children (ERN TransplantChild), including both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) programs. Between December 2022 and February 2023, healthcare professionals within the network completed a structured survey addressing microbiological screening practices and peri-transplant antimicrobial strategies in pediatric transplant recipients. Of 127 transplant programs invited, 76 (59.8%) responded, including 62 SOT and 14 HSCT programs from 36 centers across 16 European countries. Pre-transplant screening strategies, microbiological methods, and decolonization practices varied substantially between centers. Reported prevalence of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing organisms was below 10% in most programs. In SOT, perioperative prophylaxis varied according to transplanted organ type. Cephalosporins were most commonly used in kidney and heart transplantation, whereas broader-spectrum regimens, including piperacillin-tazobactam and vancomycin, were more frequently adopted in liver, intestinal, and lung transplantation. Postoperative prophylaxis was continued beyond 24 h in most SOT programs. Antifungal prophylaxis was more commonly adopted in liver, intestinal, and lung transplant recipients. In HSCT, antibacterial peri-transplant use was not routinely prescribed in a substantial proportion of programs, particularly in autologous transplantation, whereas antifungals were widely used in allogeneic HSCT. Marked heterogeneity in microbiological screening and peri-transplant antimicrobial strategies across European pediatric transplant centers underscores the need for transplant-specific, evidence-based guidelines distinguishing between SOT and HSCT settings. These findings provide a foundation for the development of shared clinical pathways and harmonized recommendations.
Kidney transplantation is the preferred treatment for suitable patients with end-stage renal disease; however, access to transplantation declines dramatically with increasing HLA sensitization. While the acceptable mismatch (AM) program by Eurotransplant improves transplantability for highly sensitized candidates, a clinically relevant subgroup with extremely low donor frequency or ineligible for AM remains disadvantaged. In carefully selected cases, the controlled delisting of unacceptable HLA antigens and the use of peri-transplant desensitization (e.g., imlifidase) may enable transplantation. In order to provide better guidance, this German expert consensus report was compiled by the Kidney and Immunology Commissions of the German Transplantation Society and the Organ Transplantation Commission of the German Society for Immunogenetics. Within the German legal framework of urgency and chances for success, the report proposes a practical guide for candidate selection, multidisciplinary governance, risk-adapted HLA delisting, assessment of organ offers, use of imlifidase, perioperative immunosuppression, prophylaxis for infection, post-transplant monitoring, and management of antibody-mediated rejection. These recommendations are intended for experienced transplant centers and aim to balance transplant opportunity against immunological risk in highly sensitized kidney transplant candidates. The primary scope of this article is highly sensitized adult wait-listed candidates considered for deceased-donor kidney transplantation after compatibility-preserving pathways have been exhausted or are unlikely to succeed; HLA-incompatible living-donor transplantation with imlifidase is addressed separately as a potential off-label scenario for selected highly sensitized patients.
Recent progress has been made toward introducing gene-edited (GE) pig heart and kidney xenotransplantation into clinical practice. In particular, the outcomes of GE pig kidney transplantation have been promising, with three recipients currently surviving between 3 and 9 months after transplantation. These encouraging results highlight the growing feasibility of xenotransplantation as a solution to the shortage of human donor organs. In the United States and many other countries, nearly half of all patients on kidney transplant waiting lists are diabetic. Individuals with diabetic nephropathy often achieve better outcomes when they receive both kidney and islet allotransplants, as this combination restores renal function and improves glucose control. Therefore, such patients would be ideal candidates for combined GE pig kidney and islet xenotransplantation. Because immunosuppressive therapy is essential to maintain a kidney graft, performing a simultaneous islet transplant is clinically justifiable. Studies in nonhuman primates have demonstrated that porcine islet transplantation can achieve long-term glucose regulation, supporting its translational potential. For the foreseeable future, until complications such as post-transplant proteinuria are fully resolved, we propose that patients with diabetic nephropathy receive a human kidney allotransplant in combination with a GE pig islet xenotransplant to optimize outcomes and improve long-term metabolic stability.
The liver transplant waitlist mortality for infants (age < 1 year) is currently the highest, listed at 20 per 100 years of waiting time. ABO incompatible (ABOi) liver-transplantation is one of the strategies to increase transplantation rate in infants but utilized only in 5.6% of infants. At our center, all children < 1 year are listed for ABOi liver transplants. If the anti-ABO titers are less than 1:8, no plasmapheresis was used. Thymoglobulin is used for induction. We analyzed the transplant outcomes of patients that received ABOi livers compared to ABOc livers. Sixteen infants, who received ABOi liver-transplants are compared to 56 ABO-compatible (ABOc) infant liver transplants. ABOi group utilized AB or B blood type livers 81%, compared to none in the ABOc group. The 1-, 5-, and 10-year survival in the ABOi group remains at 81% and is comparable to survival in the ABOc group. None of the ABOi patients developed antibody-mediated rejection or intrahepatic biliary strictures. None of the ABOi patients had hepatic artery thrombosis, compared with 4 (7.1%) in the ABOc group (p = 0.64). There is no difference in infectious complications. The median wait times for patients < 1 year for blood types A, B, AB, and were 96, 109, 82 days and 126 respectively. The patients listed to accept ABOi livers had a shorter waiting time (p = < 0.001). This study shows that ABOi liver transplants can be safely performed in children less than1 year of age without plasmapheresis, with excellent long-term outcomes.
Cytomegalovirus (CMV) is a major determinant of post-transplant morbidity in solid organ transplant recipients, not only through direct viral disease but also through a broad spectrum of indirect effects that may adversely influence graft and patient outcomes. This review summarizes current clinical and mechanistic evidence regarding the mechanisms of CMV-associated indirect injury in transplantation, drawing on human observational studies together with supporting in vitro and animal-model data. CMV establishes lifelong latency with intermittent reactivation and exerts sustained immunomodulatory effects on both innate and adaptive immunity, which may persist even during low-level viral replication. The mechanisms discussed include monocyte reprogramming, altered antigen presentation, T-cell and natural killer cell dysregulation, endothelial activation and dysfunction, chronic inflammatory signaling, impaired antimicrobial defense, and disturbances in metabolic regulation. The review considers how these mechanisms have been proposed to translate into major post-transplant complications, including acute rejection, chronic allograft dysfunction, cardiovascular and thrombotic disease, post-transplant diabetes, and increased susceptibility to secondary bacterial, fungal, and viral infections. It also addresses current preventive strategies, although evidence regarding their effectiveness in reducing indirect clinical outcomes remains limited and largely observational. Much of the supporting evidence is associative, and the contribution of CMV is often difficult to separate from that of the overall immunosuppressive burden and the comorbidities of transplant recipients. With these considerations, the available evidence supports regarding CMV not merely as an opportunistic pathogen, but as a persistent immunobiological driver of long-term transplant injury. Improved understanding of these indirect effects may enhance risk stratification, support biomarker-guided prevention, and inform future strategies aimed at reducing long-term graft dysfunction and patient morbidity after transplantation.
Small bowel obstruction (SBO) is a common surgical emergency. In transplant recipients, atypical etiologies may delay diagnosis and lead to suboptimal management. We report a case of phytobezoar-induced SBO in a liver transplant recipient and conducted a focused narrative literature review (PubMed/MEDLINE, Embase, Cochrane Library, Google Scholar, OpenEvidence, Litmaps) of adult transplant patients with mechanical SBO reported up to January 2026. A 60-year-old man with two prior liver transplantations (2012, 2022) presented with acute abdominal pain and vomiting after ingestion of wild mushrooms. Initial contrast-enhanced CT suggested adhesional SBO. After failure of conservative management, exploratory laparoscopy identified an intraluminal mass in the distal jejunum. Mini-laparotomy with enterotomy allowed extraction of a phytobezoar composed of Craterellus cornucopioides. Despite marked bowel congestion and equivocal conventional viability criteria, intraoperative indocyanine green (ICG) fluorescence confirmed adequate perfusion and avoided resection. Postoperative course was complicated by paralytic ileus, successfully reversed with neostigmine. The patient was discharged on postoperative day 14. The literature review retrieved one retrospective study and seven adult case reports; bezoars accounted for 5/7 cases, predominantly located at Roux-en-Y enteric anastomoses. ICG fluorescence had not been used in any previously reported case. Bezoars are a rare but clinically relevant cause of SBO in transplant recipients. Early surgical exploration is warranted when conservative management fails or imaging is ambiguous. Intraoperative ICG fluorescence is a useful adjunct to assess bowel viability and may avoid unnecessary resection. Individualized dietary counseling adapted to regional habits should be considered in long-term transplant follow-up. Larger contemporary series are needed to refine the etiologic spectrum and preventive strategies in this population.
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. 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. 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). 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.
Acute T cell-mediated rejection (TCMR) continues to be a major cause of graft dysfunction and loss despite advances in diagnostic methods and immunosuppression. Clinical practices regarding the treatment and follow-up of TCMR differ widely across transplant centers. The aim of our study was to describe current practices in Argentina concerning protocol biopsies, diagnosis, treatment, and follow-up of TCMR in kidney transplant patients. A national survey was conducted, promoted by the Sociedad Argentina de Trasplantes. All 58 certified kidney transplant centers in the country were invited to participate. The questionnaire, based on international surveys and adapted by local experts, explored the clinical strategies used to address TCMR. Forty-nine centers responded (84% response rate), showing high variability in the frequency of biopsies -including protocol biopsies- in the therapeutic regimens used, and in the definitions of borderline rejection and corticosteroid resistance. There is a notable heterogeneity in the management of TCMR among transplant centers in Argentina. Reaching consensus on definitions and therapeutic strategies will be essential to improve homogeneity of care and comparability across studies in our transplant centers. Introducción: El rechazo celular mediado por linfocitos T (TCMR) continúa siendo una causa relevante de disfunción y pérdida del injerto renal. A pesar de los avances en los métodos de diagnóstico y de inmunosupresión, las prácticas clínicas respecto al tratamiento y seguimiento del TCMR varían considerablemente entre distintos centros de trasplante. El objetivo de nuestro trabajo fue describir las prácticas actuales en Argentina en relación con las biopsias de protocolo (o vigilancia), el diagnóstico, el tratamiento y el seguimiento del TCMR en pacientes con trasplante renal. Materiales y métodos: Se realizó una encuesta nacional en formato digital, promovida por la Sociedad Argentina de Trasplante. Se invitó a participar a los 58 centros habilitados de trasplante renal del país. El cuestionario, basado en encuestas internacionales y adaptado por expertos locales, indagó sobre las estrategias clínicas empleadas frente al TCMR. Resultados: Respondieron 49 centros (84% de respuesta), y se evidenció gran variabilidad en la frecuencia de biopsias, incluyendo las biopsias de protocolo, en los esquemas terapéuticos utilizados y en las definiciones de rechazo borderline y de resistencia a los corticoesteroides. Conclusión: Existe una notable heterogeneidad en el manejo del TCMR entre los centros de trasplante de Argentina. Un consenso en las definiciones y las estrategias terapéuticas resultará esencial para mejorar la homogeneidad en la atención y la comparabilidad de los resultados clínicos entre los distintos centros de trasplante del país.
Intestinal transplantation requires high levels of long-term immunosuppression, putting recipients at high risk of developing malignancies. Factors influencing the incidence and outcomes of these malignancies remain poorly understood. We conducted a retrospective multicenter study surveying 11 of 15 intestinal transplantation (ITx) centers in the United States, including 336 of 451 transplants performed between 2020 and 2025. Forty-four patients developed de novo malignancies, including 34 posttransplant lymphoproliferative disorder, 5 skin carcinomas and 5 other carcinomas. Malignancy incidence was 13.1% at a mean follow-up time of 2.33 y. Overall survival did not significantly differ between all intestinal transplant recipients and those who developed malignancies. Malignancy incidence was significantly influenced by maintenance immunosuppression: tacrolimus + Steroids was associated with increased odds of malignancy and tacrolimus + mycophenolate mofetil + steroids with decreased odds. Subsequently reducing immunosuppression did not impact the incidence or severity of rejection. However, concurrent infection-especially opportunistic infection-was associated with higher mortality in the malignancy group. Malignancy after ITx is likely related to greater T-cell immunosuppression with increased incidence associated with tacrolimus-predominant maintenance regimens and improved outcomes with multimodal regimens and the absence of infections. Our results suggest that reduced T-cell suppression and maintenance of some level of immunocompetence may decrease the incidence, morbidity, and mortality of malignancy after ITx without increasing rejection rates.
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. 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). 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%. 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.
Sickle cell disease (SCD) is a chronic and life-limiting hemoglobin and systemic vascular disease. While over 1000 people have undergone hematopoietic cell transplantation (HCT) over the last 40 years, long-term disease-specific and health-related quality of life data are lacking. The American Society of Hematology 2021 Guidelines for SCD emphasized the need for more detailed registry data to inform patients and providers with decision-making and practice recommendations. In January 2021, the Sickle Cell Transplant Advocacy and Research Alliance (STAR) launched Project Sickle Cure (PSC). This multi-center, prospective study of patients who have undergone HCT for SCD includes baseline demographics and SCD-specific post-HCT outcomes, serial neurocognitive testing, health-related quality of life measures, health equity evaluations, a neuroimaging bank, detailed evaluation of neurologic status pre- and post-transplant, and chronic pain evaluation. A biorepository is in the planning stage of development. As of November 2025, 115 participants have enrolled at 18 STAR sites with enrollment ongoing. PSC is a STAR prospective study which will address a major gap in our understanding of outcomes post-HCT specific to SCD. WeDecide, a larger study comparing HCT health-related quality of life outcomes to those who receive non-transplant disease modifying therapy (NT-DMT) is in development, and PSC will provide the HCT comparator data. These data will also be highly relevant as other curative and transformative therapies, such as gene therapy, become more widely used.
Early allograft injury during the first year after kidney transplantation is a major determinant of long-term graft survival. Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) quantify donor-derived human leucocyte antigen (HLA) peptides presented to recipient CD4+ T cells via the indirect pathway and may capture alloimmune risk beyond conventional HLA mismatch. In this single-center retrospective cohort study, we evaluated adult kidney transplant recipients transplanted between 2021 and 2024. Five-locus PIRCHE-T2 (T-cell epitope load) and PIRCHE-B (surface-accessible amino acid mismatch) scores were calculated using high-resolution HLA typing with imputation when necessary. The primary endpoint was a composite of post-transplant allograft injury within one year, including donor-specific antibody (DSA) development, histologic or molecular rejection, or elevation of donor-derived cell-free DNA (dd-cfDNA). Secondary endpoints were each component analyzed separately. Predictive performance was assessed using receiver operating characteristic analysis and compared to the only HLA A/B/DR antigen mismatch model, and associations were evaluated using Cox proportional hazards models. Among 683 recipients, 250 (37%) experienced the primary endpoint. Higher five-locus PIRCHE-T2 and PIRCHE-B scores were significantly associated with the composite outcome [adjusted hazard ratio (HR)(95% confidence interval (CI)] per point increase 1.009(1.004-1.014) and 1.043(1.027-1.060), and adjusted HR low versus high risk 1.653(1.254-2.180) and 2.280(1.664-3.123), respectively). Both scores demonstrated modest discriminatory performance (area under the curve (AUC) 0.575-0.621). Higher PIRCHE scores were also independently associated with increased risk of de novo or recurrent DSA, dd-cfDNA elevation, and showed trends toward increased rejection risk. Sensitivity analyses incorporating six-locus PIRCHE-T2 (including DQA1) yielded consistent results. Compared with HLA A/B/DR antigen-mismatch models, PIRCHE-B scores improved prediction primarily for DSA, whereas PIRCHE-T2 did not add predictive value for outcomes. Higher PIRCHE scores are associated with increased risk of early alloimmune injury after kidney transplantation across multiple complementary biomarkers. Although discriminatory performance was modest, PIRCHE provides mechanistically grounded risk stratification and may complement existing immunologic assessment strategies.
Tertiary care centres offering pediatric kidney transplantation in Asia remain limited in numbers and peri-operative practices are often guided by individual experiences rather than robust evidence. Scientific analysis and sharing of these experiences across centres can help improve outcomes and guide healthcare authorities to develop context-specific, evidence-informed guidelines in limited resource settings. A cross-sectional, anonymous electronic survey was conducted via Google Forms (January-December 2025) across pediatric kidney transplant centres in South Asian lower-middle income countries (LMICs) to capture peri-operative practices. Descriptive statistics were used for analysis. A total of 22 responses were analyzed; respondents being physicians involved in pediatric kidney transplantation. The most frequently reported invasive monitoring was central venous pressure (90%) and arterial blood pressure (86%). High-volume centres (HVC- performing > 10 pediatric kidney transplants per year; n = 4) reported postoperative ICU stay of less than 24 h (p = 0.045), acceptable preoperative hemoglobin levels above 8 g/dL, target CVP of 10-12 mmHg and use of regional analgesia (p > 0.05). Eleven centres (including 50% HVC) reported using stroke volume variation or pulse pressure variation (SVV/PPV) to guide peri-operative fluid management. HVC managing younger (< 5 years) recipients (n = 4) reported CVP targets above 12 mmHg and donor-specific blood pressure goals during reperfusion. This survey highlights lack of agreement between evidence and practices regarding the use of advanced invasive monitoring (SVV/PPV), reperfusion targets, analgesic approaches and duration of postoperative ICU stay.
Although transplantation is the preferred treatment for end-stage organ disease, long-term outcomes are limited by immunosuppressive drug toxicity and immune-mediated injury. Selective in vivo expansion of regulatory T cells (Tregs) using interleukin-2 (IL-2) analogs has emerged as a strategy to induce antigen-specific transplant tolerance with fewer side effects. Herein, we investigate the therapeutic efficacy of an IL-2 mutein molecule (mIL-2) with enhanced receptor specificity and extended half-life in murine models of solid organ transplantation. mIL-2 therapy significantly improves allograft survival in an antigen-specific manner, accompanied by increased Treg activation, decreased effector T cell activation and reduced donor-specific antibody production. Transcriptional profiling reveals expansion of Tregs expressing the suppression of tumorigenicity 2 (ST2) Tregs with heightened activation status and suppressive function. Accordingly, the mIL-2-induced long-term allograft survival is abrogated in Treg-specific ST2 knockout graft recipients, underscoring the critical role of ST2+ Tregs. These findings identify mIL-2 as an approach to promote long-term transplant tolerance while reducing reliance on conventional immunosuppression.
Epstein-Barr virus (EBV) is a common trigger of secondary hemophagocytic lymphohistiocytosis (HLH), particularly in transplant recipients. Adoptive cellular therapy with EBV-specific T cells is an emerging option for refractory EBV-driven disease but may precipitate cytokine toxicities. We report a boy with a history of congenital nephrotic syndrome who in infancy underwent maternal kidney transplantation. At the age of 6 years, he developed monomorphic EBV-positive post-transplant lymphoproliferative disorder, followed by EBV-driven HLH. Despite etoposide- and steroid-based HLH therapy, IVIG, anakinra, and a maternal virus-specific T-cell infusion, he showed recurrent hyperinflammation. After a single dose of the allogeneic EBV-specific T-cell product tabelecleucel (Ebvallo) and exacerbation of HLH, he experienced cytokine release syndrome and neurotoxicity with acute liver failure, coagulopathy, and renal failure. He died from refractory lactic acidosis and multiorgan failure. This case highlights the therapeutic complexity of EBV-HLH in a solid-organ transplant recipient and underscores both the rationale for and risks of cellular immunotherapy amid severe hyperinflammation and organ dysfunction.
Immunological risk prediction in solid organ transplantation has long depended on threshold-based representation of histocompatibility data: donor-specific antibodies (DSA) reported as positive or negative, mean fluorescence intensity (MFI) assessed by fixed cutoffs, molecular mismatch assigned at transplantation, and assays interpreted at a single time point. Although practical, these conventions simplify the complex and dynamic nature of the immune response. In this perspective, we argue that as machine learning (ML) algorithms and computational approaches enter the field of transplant immunology, we need to focus on whether the inputs that feed into these tools and models reflect how alloimmunity actually behaves. We propose treating alloimmune risk as a time-indexed alloimmune state, updated whenever new data are available, across four domains: antibody profile, molecular mismatch and predicted immunogenicity, recipient immune context, and graft context. Within this framework, the features that experienced clinicians and histocompatibility experts already track (e.g., DSA velocity, persistence, epitope spreading, concordance with graft injury) become computable rather than implicit. We discuss how moving from thresholds to trajectories impacts model design, why HLA laboratory expertise becomes more important rather than less, and why interpretability, regulation, and external validation should precede clinical adoption.
Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and outcome. Results: The patient developed rapidly progressive epidermal detachment with severe oral, ocular, and genital mucosal involvement shortly after exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Disease severity was reflected by a SCORTEN score of 5, corresponding to a very high predicted mortality risk. The clinical picture raised concern for both TEN and severe acute GVHD, while histopathological findings favored TEN but were not definitive. Management included systemic corticosteroids, intravenous immunoglobulin, ruxolitinib, and intensive supportive care. The patient gradually re-epithelialized and recovered without long-term sequelae. Conclusions: This case underscores the diagnostic difficulty of distinguishing TEN from severe acute GVHD in the early post-transplant period. Careful assessment of drug exposure, clinical evolution, and multidisciplinary evaluation are essential to guide timely and appropriate management.
Cardiovascular disease remains the leading cause of mortality in kidney transplant recipients (KTRs). Arterial hypertension is present in a vast majority of patients after kidney transplantation, constituting the most prevalent cardiovascular comorbidity, and is a significant modifiable risk factor for other cardiovascular complications and graft loss. The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not address blood pressure control strategies in KTRs, and the prior 2021 KDIGO recommendations targeting values below 130/80 mmHg rely primarily on data extrapolated from non-KTR populations. This represents an existing evidence gap in the management of post-transplant hypertension. Dihydropyridine calcium channel blockers and angiotensin receptor blockers remain first-line antihypertensive medications, although most studies assessing their effectiveness in KTRs date back more than 15 years. The current treatment guidelines are based largely on limited and outdated data. Optimal selection and individualization of immunosuppressive therapy and-when feasible-its modification in some KTRs may be important in improving blood pressure control. This includes, for example, a reduction in the calcineurin inhibitor or steroid dose, as well as the use of mTOR inhibitors or belatacept. The lack of large, up-to-date randomized trials in the KTR population underscores the pressing need for further extensive research focused on this patient group.
Background Cytomegalovirus (CMV) infection is a major contributor to morbidity and mortality in recipients of hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), and chimeric antigen receptor T-cell (CAR-T) therapy. While antiviral agents remain the cornerstone of treatment, CMV-specific immunoglobulins (CMVIG) have been utilized as adjunct therapy with variable outcomes. This study aims to evaluate the virological response and tolerability of CMVIG in cases of severe or refractory CMV viremia, with or without CMV disease. We conducted a single-center retrospective case series of adult recipients of SOT, allogeneic HSCT, and/or CAR-T cell therapy who developed CMV viremia or disease and received at least one dose of CMVIG between May 2017 and May 2023 at our center. Virological improvement within 14 days of starting CMVIG and tolerability of CMVIG are the primary outcome of this study. A total of 33 patients were included. Of these, 29 underwent transplantation [SOT: 48.2%, HSCT: 51.7%], and five underwent CAR-T cell therapy (one post-HSCT). High-risk CMV serostatus was present in 12%. CMV viremia was documented in 32 patients (97%), and tissue-invasive disease was present in 11 patients (33.3%). Virological response, was observed in 65.6% of the cohort. The median time to undetectable CMV viral load following CMVIG initiation was 28 days. CMVIG was well-tolerated. All-cause mortality at 90 days remained high (57%). In this case series, CMVIG demonstrated a virological response rate of 65.6% in patients with severe or refractory CMV infection. While CMVIG was well-tolerated with minimal adverse events, the high mortality rate despite virological response suggests that CMVIG may be insufficient for this critically ill population. Our findings should be interpreted as observational data from a small case series, and prospective controlled trials are needed to establish the true benefit of CMVIG in combination with standard antiviral therapy.
Advancements in frontline therapies have substantially improved outcomes in newly diagnosed multiple myeloma (NDMM); however, many patients will not achieve deep responses and will relapse. Teclistamab, a BCMA×CD3 bispecific antibody, in combination with daratumumab, has demonstrated strong efficacy in relapsed/refractory multiple myeloma versus standard of care as early as first relapse. This ongoing phase 2 GMMG-HD10/DSMM-XX (MajesTEC-5) study evaluates teclistamab-based regimens in transplant-eligible NDMM. In this prespecified pooled analysis of three cohorts, 49 patients received teclistamab/daratumumab/lenalidomide (Tec-DR; arms A and A1) or Tec-DR with bortezomib (Tec-DVR; arm B). Primary endpoints were incidence and severity of adverse events (AEs) and serious AEs; secondary endpoints included overall response rate (ORR), minimal residual disease (MRD) negativity and MRD-negative complete response (CR). The current analysis spans the induction and autologous stem cell transplantation phases until the premaintenance timepoint. Grade 3 or 4 treatment-emergent AEs (TEAEs) occurred in 91.8% (45/49); most were hematologic (lymphopenia (59.2%; 29/49), neutropenia (59.2%; 29/49) and leukopenia (18.4%; 9/49)). No grade 5 TEAEs were reported. Serious AEs occurred in 55.1% (27/49); pyrexia (12.2% (6/49)) was most common. Any-grade and grade 3 or 4 infections occurred in 81.6% (40/49) and 36.7% (18/49), respectively, the most common grade 3 or 4 infections being COVID-19 and pneumonia (6.1% (3/49) each). Cytokine release syndrome occurred in 67.3% (33/49); all were grade 1 or 2, all resolved and none led to discontinuation of any study treatment. No treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) events occurred. Across arms, the MRD-negative CR rate was 91.8% (45/49) by the premaintenance timepoint; the MRD negativity rate was 100% in evaluable samples at postinduction cycle 3 (1 × 10-5 (46/46)), cycle 6 (1 × 10-5 (46/46) and 1 × 10-6 (46/46)) and premaintenance (1 × 10-5 (40/40)); the ORR was 100% (49/49). Total median stem cell yield was 8.1 × 106 per kg. Data support the feasibility of Tec-D(V)R induction in transplant-eligible NDMM, with a consistent safety profile compared with individual regimen components and notable early MRD negativity rates. ClinicalTrials.gov identifier: NCT05695508 .