Transplantation and Cellular Therapy最新文献

{"title":"Hyponatremia After CAR T-Cell Therapy: Biomarker or Therapeutic Target?","authors":"Lawrence Cheng Kiat Ng, Tertius Tansloan Tuy, Jing Yuan Tan, Yunxin Chen, Francesca Wei Inng Lim","doi":"10.1016/j.jtct.2026.09.043","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.09.043","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyomavirus-Specific T Cells in Progressive Multifocal Leukoencephalopathy: A Multicenter Retrospective Analysis","authors":"Alexandre Chevalier,&nbsp;Baptiste Bonneau,&nbsp;Lea Grote-Levi,&nbsp;Nora Möhn,&nbsp;Paola Cinque,&nbsp;Jeremy D. Rubinstein,&nbsp;Rebecca Wicklein,&nbsp;Thomas Pfeiffer,&nbsp;Bilal Omer,&nbsp;Maximilian Steinhardt,&nbsp;Jean-Jacques Tudesq,&nbsp;Nathalie Testard,&nbsp;Patrice Chevallier,&nbsp;Raphael Bernard-Valnet,&nbsp;Marion Le Maréchal,&nbsp;Gaia Catalano,&nbsp;Béatrice Pignolet,&nbsp;Agnès Sommet,&nbsp;Britta Eiz-Vesper,&nbsp;Patrizia Comoli,&nbsp;Guillaume Martin-Blondel","doi":"10.1016/j.jtct.2026.06.015","DOIUrl":"10.1016/j.jtct.2026.06.015","url":null,"abstract":"<div><div>Progressive multifocal leukoencephalopathy (PML) is a rare brain infection caused by JC polyomavirus (JCPyV) in immunocompromised individuals, for which no effective antiviral therapy exists. Diverse cellular therapy approaches using polyomavirus-specific T cells (PyVST) has emerged as a therapeutic option. We aimed to evaluate the real-world effectiveness of PyVST in patients with PML. We retrospectively analyzed 64 patients from 13 centers who received PyVST alongside standard care. Conditions predisposing to PML included mainly hematologic malignancies (33/64, 51.6%). One-year survival was 62% (36/58) when excluding patients whose deaths were unrelated to PML. Most patients received BK virus–specific T cells (55/64, 84.6%), isolated mainly via Interferon-γ capture system (37/64, 57.8%), and from related donors (32/64, 50%). At therapy initiation, survivors had lower modified Rankin scale (3 [IQR 3 to 4] versus 4 [IQR 4 to 5], <em>P</em> = .0317) and lower cerebrospinal fluid (CSF) JCPyV DNA (3.03 [IQR 2.66 to 3.47] versus 4.29 [IQR 3.31 to 4.79] log₁₀ copies/mL, <em>P</em> = .0037) compared to non survivors. In multivariate analysis performed on 38 patients with complete data, only CSF JCPyV DNA level was associated with survival (<em>P</em> = .0266). No manufacturing characteristic or HLA-matching were associated with outcome. Adverse events were rare, with PML-associated immune reconstitution inflammatory syndrome reported in 5/64 patients (7.8%) and rash in 2/64 patients (3.1%). In this uncontrolled analysis, adoptive T cell therapy yielded encouraging 1-year survival rates in patients with PML and demonstrated a favorable safety profile. Important questions remain regarding the optimal strategy for T-cell generation, as well as the specific product and recipient characteristics most likely to influence treatment outcomes.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1315.e1-1315.e11"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neighborhood Socioeconomic Disadvantage and Distance From Treatment Center do not Impact Survival Outcomes of Patients With Non-Hodgkin Lymphoma and Multiple Myeloma Treated With CAR T-Cell Therapies","authors":"Agrima Mian,&nbsp;Rafaella Litvin,&nbsp;Danai Dima,&nbsp;Betty K. Hamilton,&nbsp;Allison Winter,&nbsp;Jack Khouri,&nbsp;Louis Williams,&nbsp;Shahzad Raza,&nbsp;Deepa Jagadeesh,&nbsp;Aaron T. Gerds,&nbsp;Robert M. Dean,&nbsp;Ronald M. Sobecks,&nbsp;Faiz Anwer,&nbsp;Matt E. Kalaycio,&nbsp;Claudio G. Brunstein,&nbsp;Craig S. Sauter,&nbsp;Marcelo Pasquini,&nbsp;Brian T. Hill,&nbsp;Paolo F. Caimi","doi":"10.1016/j.jtct.2026.05.039","DOIUrl":"10.1016/j.jtct.2026.05.039","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment of relapsed/refractory (r/r) hematologic malignancies but are largely delivered at specialized academic centers. Socioeconomic and geographic factors may influence access to these therapies and potentially impact outcomes. While neighborhood disadvantage has been associated with worse health outcomes, its impact on survival following CAR T-cell therapy remains unclear. We conducted a retrospective study of adult patients with r/r B-cell non-Hodgkin lymphoma (B-NHL) and multiple myeloma (MM) treated with CAR T-cell therapy at a single academic center. Neighborhood socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), with higher scores indicating greater disadvantage. Distance to treatment center (DTC) was calculated from patient residence. Overall survival (OS) and progression-free survival (PFS) were compared by ADI and DTC using Kaplan–Meier estimates and Cox proportional hazards models. A total of 124 B-NHL and 45 MM patients received CAR T-cell therapy between 2018 and 2023. Median ADI was 62.5 and median DTC was 42.5 miles. Longer DTC was associated with higher ADI (<em>P</em> &lt; .001). No significant differences in OS, PFS, or response rates were observed between high- and low-ADI groups for either B-NHL (median OS: 19 versus 14 mo; <em>P</em> = .50) or MM (median OS: 14 versus 18 mo; <em>P</em> = .60). Similarly, survival did not differ between patients with long versus short DTC for B-NHL (median OS: 19 versus 14 mo; <em>P</em> = .40) or MM (median OS: 14 versus 20 mo; <em>P</em> = .90). Dichotomizing ADI into the highest 15% versus lower 85% also showed no impact on outcomes. In this single-center cohort of patients who received CAR T-cell therapy, neighborhood disadvantage and distance to the treatment center were not associated with differences in survival outcomes. Although selection and referral biases likely influence which patients ultimately receive therapy, these findings suggest that once access to CAR T-cell therapy is achieved, outcomes may be comparable across socioeconomic and geographic groups. Improving equitable referral pathways and access to specialized centers remains essential.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1354.e1-1354.e6"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Analysis of Skin Responses per 2014 NIH Response Criteria and Modified 2025 NIH Skin Task Force Response Criteria in Patients With Sclerotic Chronic Graft-Versus-Host Disease","authors":"Amila Kapetanovic,&nbsp;Rania Hishmeh,&nbsp;Anita Stokes,&nbsp;Edward W. Cowen,&nbsp;Steven Z. Pavletic,&nbsp;Najla El Jurdi","doi":"10.1016/j.jtct.2026.06.019","DOIUrl":"10.1016/j.jtct.2026.06.019","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1359.e1-1359.e4"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide Centralized Manufacturing and Fresh Distribution of TCRαβ/CD19-DepletedGrafts: A Real-World French Experience","authors":"Ugo Chartral,&nbsp;Mony Fahd,&nbsp;Emma Gasperment,&nbsp;Charlotte Calvo,&nbsp;Martin Castelle,&nbsp;Elvira Duchesne,&nbsp;Aurélie Gabrion,&nbsp;Cécile Roudaut,&nbsp;Chloé Mollet,&nbsp;Brigitte Ternaux,&nbsp;Maxime Bouabdelli,&nbsp;Eden Schwartz,&nbsp;François Lefrère,&nbsp;Despina Moshous,&nbsp;Vincent Barlogis,&nbsp;Anne Charlotte Teyssier,&nbsp;Boris Calmels,&nbsp;Clemence Demerle,&nbsp;Anne-Line Chateau,&nbsp;Nimrod Buchbinder,&nbsp;Jean Sébastien Diana","doi":"10.1016/j.jtct.2026.05.035","DOIUrl":"10.1016/j.jtct.2026.05.035","url":null,"abstract":"<div><div>TCRαβ/CD19 depletion enables mismatched and haploidentical hematopoietic stem cell transplantation (HSCT) without the use of a post-transplant alkylating agent and is particularly relevant for pediatric nonmalignant disorders. However, the complexity of graft engineering limits its availability to specialized centers. Indeed, implementing such a process and obtaining regulatory approval are resource-intensive endeavors that require sufficient patient volume. To address these limitations, we established a centralized platform for the real-time nationwide distribution of fresh TCRα/β/CD19-depleted grafts in France, prioritizing bringing the cells to the patients, rather than the patients to the cells. This study aimed to evaluate the feasibility and challenges of this unique model of centralized, nationwide manufacturing of fresh TCRαβ/CD19-depleted grafts. In this retrospective cohort study (2014 to 2025), after on-site or off-site collections, all haploidentical or mismatched unrelated donors that underwent TCRα/β/CD19 depletion were manufactured at a single academic facility and delivered to nationwide transplant centers. Manufacturing performance, product compliance, logistics (vein-to-vein and delivery times), and early hematologic recovery were analyzed and compared for 10 transplant centers. A total of 55 products were distributed after undergoing TCRα/β/CD19 depletion for Inborn Errors of Immunity (n = 36), DNA repair/bone marrow failure (n = 15), and malignancies (n = 4). Despite significant heterogeneity in starting apheresis materials across different collection centers, manufacturing performance was robust and reliable, with comparable CD34+ recovery, TCRαβ, and CD19 depletion efficacy between on-site and off-site collections. Infused CD34 dose was similar between on-site and off-site apheresis (9.81 × 10⁶/kg versus 9.91 × 10⁶/kg), and TCRα/β doses were &lt;1 × 10⁵ in 96% of products. Vein-to-vein time met the &lt;36-h target in 52/55 cases (95%), including the majority of off-site collection and infusion procedures. Delivery time remained within the &lt;6-h specification for all on-site infusions and 14/16 off-site infusions. Early neutrophil and platelet recovery were comparable between groups, with identical 50% recovery times of 15 days post-HSCT. Centralized fresh manufacturing and nationwide distribution of TCRαβ/CD19-depleted grafts are feasible, safe, and logistically robust. This approach represents a valuable intermediate model between local fresh production and centralized cryopreserved manufacturing, particularly in light of the reported limitations of cryopreservation on graft quality and immune effector cell integrity. It may provide a scalable organizational framework for other academic cellular therapy and ATMP platforms.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1252.e1-1252.e12"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Transplantation in the Rare Disease Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Neutrophilia: Age and Disease Burden Determine Outcome","authors":"Annemarie Mohring,&nbsp;Katja Sockel,&nbsp;Christian Thiede,&nbsp;Jan Schröder,&nbsp;Daniel Wolff,&nbsp;Marina Kadantsev,&nbsp;Marek Werth,&nbsp;Markus Schneider,&nbsp;Tabea Globuschuetz,&nbsp;Georg Nikolaus Franke,&nbsp;Sebastian Klein,&nbsp;Joachim Göthert,&nbsp;Cort Hendrik Claassen,&nbsp;Gesine Bug,&nbsp;H. Christian Reinhardt,&nbsp;Anna Hecht-So,&nbsp;Katharina S. Götze,&nbsp;Sarah Flossdorf,&nbsp;Wolfgang Bethge,&nbsp;Martin Bornhäuser,&nbsp;Christina Rautenberg","doi":"10.1016/j.jtct.2026.06.027","DOIUrl":"10.1016/j.jtct.2026.06.027","url":null,"abstract":"<div><div>Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with neutrophilia, as termed by the World Health Organization (WHO) in 2022 [<span><span>1</span></span>], formerly known as <em>atypical chronic myeloid leukemia</em> (aCML) [<span><span>2</span></span>], is a rare hematologic malignancy with a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative treatment, but prognostic factors for post-transplantation outcomes are poorly defined.</div><div>This retrospective multicenter analysis included 85 patients receiving allografts over a 30-year period at 8 German centers, representing the largest cohort reported at this writing. Univariable and multivariable analyses were performed to identify prognostic factors for post-transplantation outcome. Endpoints were overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM). After a median follow-up of 7.6 years, 5-year OS, RFS, CIR, and NRM were 47%, 37%, 32%, and 29% respectively. Age ≥50 years and bone marrow (BM) blasts ≥5% were associated with inferior OS and RFS in univariable analyses, whereas a hemoglobin level of &lt;8 g/dL adversely affected RFS. In our multivariable analysis, younger age remained an independent predictor for improved OS and RFS, whereas a higher Hb level was associated with superior RFS. Additionally, <em>EZH2</em> and <em>TET2</em> mutations were linked to increased relapse risk and inferior RFS, whereas <em>TET2</em> mutations also negatively impacted OS. Although limited by its retrospective character, small sample size, and incomplete molecular data, this study shows that long-term survival after allo-HCT is achievable in patients with MDS/MPN with neutrophilia, particularly in younger individuals with low disease burden. However, relapse and NRM remain major challenges, underscoring the need for optimized post-transplantation strategies.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1301.e1-1301.e10"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Evaluation of Single-Dose and Split-Dose Melphalan Conditioning Concerning Toxicity Profiles and Engraftment Kinetics: A Propensity Score-Matched Analysis","authors":"Ceren Uzunoğlu Güren,&nbsp;Derya Demirtaş,&nbsp;Ezel Elgün,&nbsp;Tuğçe Bulun,&nbsp;Elif Suyanı,&nbsp;Bilal Aygün,&nbsp;Didar Yanardağ Açık,&nbsp;Fahir Özkalemkaş,&nbsp;Vildan Özkocaman,&nbsp;Asu Fergün Yılmaz,&nbsp;Ayşe Tülin Tuğlular,&nbsp;Işık Atagündüz,&nbsp;Tayfur Toptaş","doi":"10.1016/j.jtct.2026.05.044","DOIUrl":"10.1016/j.jtct.2026.05.044","url":null,"abstract":"&lt;div&gt;&lt;div&gt;High-dose melphalan (HDM) remains the gold-standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), significantly improving response depth and long-term survival. However, HDM is associated with substantial toxicities, notably oral mucositis and gastrointestinal complications. To mitigate these, centers vary the administration schedule between a single bolus (200 mg/m²) or a split-dose approach over 2 days. Existing literature comparing these methods is limited and inconsistent regarding both toxicity and engraftment kinetics. This study compares the safety profiles, hematologic recovery kinetics, and long-term clinical outcomes (progression-free survival and overall survival) of single-dose versus split-dose HDM administration in patients with MM undergoing ASCT, utilizing a propensity score-matched analysis to minimize baseline imbalances. This multicenter retrospective cohort study included 262 patients across 3 tertiary centers between 2016 and 2026. To ensure comparability, 202 patients were selected through 1:1 propensity score matching (PSM). PSM was performed using logistic regression including age, sex, ECOG status, ISS stage, and renal function (eGFR &lt;40 versus ≥40 mL/min/1.73 m²). The primary safety endpoint was severe gastrointestinal (GI) toxicity (grade ≥3 mucositis and/or diarrhea). Secondary endpoints included infections, organ toxicities, engraftment timing, and survival. To delineate the independent contributions of dosing schedule and melphalan to cell infusion timing (24 versus 48 hours), multivariable linear regression and Cox proportional hazards models were employed, adjusting for CD34⁺ cell dose and maintenance therapy. Single-dose administration was associated with a significantly lower incidence of severe GI toxicity (19.8% versus 36.6%; odds ratio [OR] .43, 95% confidence interval [CI] .21–.84; &lt;em&gt;P&lt;/em&gt; = .012), primarily driven by reduced grade ≥3 diarrhea (OR .40, 95% CI .19 to .81; &lt;em&gt;P&lt;/em&gt; = .009). Single-dose dosing also provided significant protection against organ toxicities, specifically reducing creatinine elevation (OR .31; &lt;em&gt;P&lt;/em&gt; = .025) and hepatic transaminase elevation (OR .40; &lt;em&gt;P&lt;/em&gt; = .043). Although split-dose conditioning initially showed faster neutrophil (11 versus 12 days; &lt;em&gt;P&lt;/em&gt; &lt; .001) and platelet engraftment (11 versus 13 days; &lt;em&gt;P&lt;/em&gt; &lt; .001), multivariable models revealed this was exclusively driven by the 48-hour melphalan to cell infusion interval used in a subgroup of the split-dose cohort. No significant differences were observed between single-dose and split-dose 24-hour subgroups. At Day +90, overall response rates (94.1% versus 93.8%) and CR rates (71.3% versus 64.4%) were comparable (&lt;em&gt;P&lt;/em&gt; = .48). With a median follow-up of 36.5 months, no significant differences were found in median PFS (33.6 versus 34.7 months; &lt;em&gt;P&lt;/em&gt; = .552) or OS (&lt;em&gt;P&lt;/em&gt; = .598). Single-dose HDM provides a superior saf","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1283.e1-1283.e11"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Early Immunosuppression as CRS Prophylaxis in Outpatient Haploidentical Transplants: A Randomized Phase II Study”","authors":"Candana Maji,&nbsp;Hariharan Srinivasan,&nbsp;Aishwarya Biradar,&nbsp;Reenoo Jauhari","doi":"10.1016/j.jtct.2026.02.003","DOIUrl":"10.1016/j.jtct.2026.02.003","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1356.e1-1356.e2"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Acute Graft-Versus-Host Disease and Delayed Hematopoietic Recovery on the Incidence and Clinical Burden of Late Cytomegalovirus Reactivation and Disease after Letermovir Prophylaxis during the First 100 Days after Cord Blood Transplantation","authors":"Naoki Okada,&nbsp;Hiroyuki Muranushi,&nbsp;Junya Kanda,&nbsp;Tadakazu Kondo,&nbsp;Yasuyuki Arai,&nbsp;Takeshi Maeda,&nbsp;Yasuko Miyahara,&nbsp;Haruka Okamoto,&nbsp;Hiroki Amagase,&nbsp;Akihito Yonezawa,&nbsp;Toshiyuki Kitano,&nbsp;Kazuhiro Yago,&nbsp;Kazunori Imada,&nbsp;Tomoharu Takeoka,&nbsp;Ikue Okamura-Shiki,&nbsp;Takashi Ikeda,&nbsp;Kouhei Yamashita,&nbsp;Akifumi Takaori-Kondo,&nbsp;Kyoto Stem Cell Transplantation Group (KSCTG)","doi":"10.1016/j.jtct.2026.06.020","DOIUrl":"10.1016/j.jtct.2026.06.020","url":null,"abstract":"<div><div>Cord blood transplantation (CBT) is associated with a particularly high risk of cytomegalovirus (CMV) complications due to delayed immune reconstitution. While letermovir (LTV) prophylaxis is effective in the CBT setting, late CMV reactivation following LTV completion is frequent, and late CMV disease is a serious clinical concern. However, specific risk factors for late CMV reactivation or disease following LTV discontinuation within the CBT population remain poorly defined. We conducted a multicenter retrospective study of 109 CMV-seropositive adult patients from the Kyoto Stem Cell Transplantation Group who underwent CBT between 2018 and 2023, and completed LTV prophylaxis during the first 100 days after transplantation. Patients who experienced CMV reactivation, CMV disease, or death before day 100 were excluded. We evaluated the 1-yr cumulative incidences of late CMV reactivation and disease after transplantation, and assessed their risk factors and subsequent clinical impact. The 1-yr cumulative incidence of late CMV reactivation was 47.9%, occurring at a median of 37.5 days after LTV completion. Multivariate analysis identified grade II to IV acute graft-versus-host disease (aGVHD) (hazard ratio [HR] 1.95; <em>P</em> = .022) and delayed neutrophil recovery (&gt;18 days) (HR 1.81; <em>P</em> = .046) as independent risk factors for late CMV reactivation. The 1-yr cumulative incidence of late CMV disease was 5.2%. Risk factors for late CMV disease included grade II to IV aGVHD (<em>P</em> = .0045), delayed platelet recovery of 50 × 10⁹/L (&gt;43 days) (<em>P</em> = .014), and higher-dose corticosteroids at day 100 (<em>P</em> = .047). Furthermore, grade II to IV aGVHD, delayed neutrophil recovery, and delayed platelet recovery of 50 × 10⁹/L were significantly associated with recurrent late CMV reactivation (<em>P</em> = .013, 0.041, and 0.049, respectively), and grade II to IV aGVHD and delayed neutrophil recovery showed a trend toward prolonged duration of anti-CMV therapy (<em>P</em> = .092 and 0.070, respectively). Grade II to IV aGVHD and delayed hematopoietic recovery are major risk factors for late CMV reactivation and disease in CBT recipients following LTV prophylaxis during the first 100 days post-transplantation. These factors are associated with an increased clinical burden, characterized by recurrent late CMV reactivation and prolonged duration of anti-CMV therapy. Extended LTV prophylaxis is recommended for the CBT population and is particularly essential for patients harboring these high-risk clinical factors.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1307.e1-1307.e15"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and Safety of a Novel CD19-Directed CAR T-Cell Therapy in Patients with R/R B-Cell Non-Hodgkin Lymphoma","authors":"Steven M. Bair,&nbsp;Navin Pinto,&nbsp;Andrew Roth,&nbsp;Michael Verneris,&nbsp;Bradley Haverkos,&nbsp;Andrew Nicklawsky,&nbsp;Angela Ohm,&nbsp;Kimberly Jordan,&nbsp;Lindsey A. Murphy,&nbsp;Russell Marians,&nbsp;Rebecca Mallo,&nbsp;Rimas Orentas,&nbsp;Cheri Adams,&nbsp;Manali Kamdar,&nbsp;Terry Fry","doi":"10.1016/j.jtct.2026.06.002","DOIUrl":"10.1016/j.jtct.2026.06.002","url":null,"abstract":"<div><div><em>Relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (NHL)</em> present significant treatment challenges for both patients and clinicians. Despite advances in therapeutic approaches, including the approval of several chimeric antigen receptor (CAR) T-cell products in recent years, there remains a need for more effective options that improve upon existing therapies. To address this, we tested a CAR T-cell construct (UCD19) that incorporates a novel TNFRSF19 transmembrane domain alongside the FMC63 variable region and 4-1BB and CD3-zeta domains that have been used in approved CAR T-cell products manufactured in IL-7 and IL-15 in patients with R/R NHL. The primary aim of this phase 1 clinical trial was to evaluate the manufacturing feasibility and safety profile of the UCD19 product. The secondary aim was to evaluate preliminary efficacy. <em>This trial was an</em> open-label, single arm, single site, phase 1 study designed to assess the safety and feasibility of manufacturing and administration of UCD19 CAR T-cells. Ten patients ≥18 years with R/R B-cell NHL were infused with a fixed dose of UCD19 CAR T-cells (two dose levels) following standard lymphodepleting chemotherapy. Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were observed in 30% and 10% of subjects, respectively; all were grades 1 or 2. There were no grade 3 or higher CRS/ICANS. Overall response rate was 90% across the cohort, with a CR rate of 70% at 90 days, with 60% remaining in remission at 12 months. These results demonstrate favorable safety and preliminary efficacy, supporting further investigation of the novel UCD19 CAR T-cell therapy in larger clinical trials to confirm its safety and efficacy in patients with R/R B-cell NHL. This trial was registered at <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span> as #NCT04240808.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 10","pages":"Pages 1268.e1-1268.e12"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}