Transplantation and Cellular Therapy最新文献

{"title":"Advances in CAR-T and CAR-NK cell therapy in follicular lymphoma: a review.","authors":"Sijia Yan, Wanying Liu, Mi Zhou, Yi Xiao","doi":"10.1016/j.jtct.2026.10.001","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.001","url":null,"abstract":"<p><p>Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma and is characterized by prolonged survival but recurrent relapses. The unmet need is greatest among patients with high-risk disease, including progression of disease within 24 months of first-line immunochemotherapy (POD24), double-refractory disease, histologic transformation, and exposure to multiple previous lines of therapy. In pivotal single-arm studies enrolling heavily pretreated patients, CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies produced overall response rates of 86-97% and complete response rates of 68-94%, with durable disease control in a substantial proportion of patients. However, autologous CAR-T therapy is limited by individualized manufacturing, the potential need for bridging therapy, intensive monitoring, unique toxicities, and restricted access outside specialized centers. This review summarizes the efficacy and safety of approved CAR-T products in relapsed/refractory FL, explains how differences in receptor architecture and costimulatory signaling may affect cellular kinetics and toxicity, and discusses emerging alternative targets, dual-target constructs, combination strategies, and CAR-natural killer (CAR-NK) cell platforms. CAR-NK cells represent a promising investigational off-the-shelf platform; however, current clinical evidence is derived predominantly from early-phase studies involving heterogeneous B-cell malignancies, with limited FL-specific data. Their efficacy, durability, safety, and scalability in FL therefore remain to be established in dedicated clinical studies.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172064","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":"Considerations for Improving Equity and Access to CAR-T Therapies.","authors":"Eddie Hp Tan, Mickey Bc Koh","doi":"10.1016/j.jtct.2026.10.011","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.011","url":null,"abstract":"<p><p>There are significant barriers to equitable access to cell therapies among which include the high costs of treatment, complex logistics from manufacture to bedside and the substantial economic gradients that exist between health systems of countries. Beyond the immediate issues of cost and safety balanced with efficacy, there exists a multifactorial interplay of factors which include patient and caregiver, provider and institutional, manufacturer and supply-chain, as well as regulatory or payer factors which all contribute to equity and access. With the continued evolution of advanced therapy offerings, a paradigm shift in thinking is required among policy makers, beyond the traditional drug product based regulatory frameworks and health systems. Four Key Drivers of the Paradigm shift: (1) New Manufacturing Models, (2) Technological Advancements, (3) Innovative Regulatory Approaches and (4) International Cooperation.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168596","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":"Abatacept in combination with ATLG reduces acute GvHD incidence and improves outcomes of children transplanted from mismatched unrelated donors: a real-world, multicenter, retrospective study.","authors":"Francesco Quagliarella, Matteo Becci, Jochen Buechner, Marco Becilli, Marco Zecca, Maria Ester Bernardo, Giovanna Lucchini, Riccardo Masetti, Salvatore Perdichizzi, Maura Faraci, Manuela Tumino, Franca Fagioli, Maria Giuseppina Cefalo, Ingvild Heier, Emilia Boccieri, Marco Andreani, Daria Pagliara, Franco Locatelli, Mattia Algeri, Pietro Merli","doi":"10.1016/j.jtct.2026.10.009","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.009","url":null,"abstract":"<p><strong>Background: </strong>The use of HLA-mismatched donors has been associated with increased risk of both acute and chronic Graft versus Host Disease (GvHD). The use of abatacept (ABA) reduces the risk of acute GvHD. ABA data in pediatric patients and in combination with serotherapy are limited.</p><p><strong>Objective: </strong>We hypothesized that adding ABA to the standard European GvHD prophylaxis with calcineurin inhibitor (CNI), short-course methotrexate (MTX) and anti-T-lymphocyte globulins (ATLG) would result in a lower incidence of acute GvHD and improve survival outcomes.</p><p><strong>Study design: </strong>We retrospectively analyzed data from 8 pediatric centers on consecutive patients transplanted from an HLA-mismatched unrelated donor who received ABA. The drug was added to standard GvHD pharmacological prophylaxis, including CNI, MTX and ATLG. Besides the classical 4-dose schedule, extended administration was performed (6 total doses).</p><p><strong>Results: </strong>Between February/2021 and July/2025, 91 pediatric/young adult patients with malignant or non-malignant diseases received ABA. The cumulative incidence (CI) of grade II-IV and grade III-IV acute GvHD were 24.4% and 6.9%, respectively. CI of grade II-IV acute GvHD was higher, but not statistically significant, in patients who received four doses of ABA as compared to those treated with six doses (38.1% vs 19.9%, p=0.08). CI of chronic GvHD was 29.6%, with no difference according to ABA schedule. In children with malignant diseases, relapse incidence was lower in patients receiving extended-course ABA compared to those who received 4 doses (6.9% vs 39.7%, p=0.008), resulting in improved 3-year event-free survival (88.2% vs 44.9%, p=0.001) and overall survival (OS, 91% vs 72.8 p=0.008). Among the 35 patients with non-malignant diseases, OS was 95.7%. No increased incidence of infections was observed, with the exception of EBV reactivation. Finally, we compared the outcomes of the malignant group with those of a comparable cohort from AIEOP-HSCT network, transplanted with the same approach (with the exception of ABA). Three-year GVHD/Relapse-Free Survival was 59.3% for the present cohort and 35.8% for the historical one (p=0.006).</p><p><strong>Conclusions: </strong>Our data indicate that in patients undergoing mismatched HSCT, ABA, added to a standard GvHD prophylaxis, is a suitable option for preventing GvHD, without impairing the graft-versus-leukemia effect.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149321","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 Donor Age on Transplant Outcomes in Matched Unrelated Donor Transplantation for Myelofibrosis.","authors":"Kazuki Sakatoku, Yutaka Shimazu, Makoto Murata, Tetsuya Nishida, Shuichi Shirane, Keisuke Kataoka, Naoyuki Uchida, Masashi Sawa, Jun Ishikawa, Masaya Maegaki, Yoshinobu Kanda, Shingo Yano, Masatsugu Tanaka, Shohei Yoshida, Yasuo Mori, Makoto Yoshimitsu, Hideki Nakasone, Takahiro Fukuda, Marie Ohbiki, Yoshiko Atsuta, Takayoshi Tachibana","doi":"10.1016/j.jtct.2026.10.007","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.007","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF), and donor selection remains one of the few modifiable determinants of outcome. As the unrelated donor pool ages, the impact of donor age in matched unrelated donor (MUD) HCT for MF has become increasingly relevant but remains undefined.</p><p><strong>Objective: </strong>To evaluate the impact of donor age on engraftment, graft-versus-host disease (GVHD), and survival after MUD HCT for primary MF, and to examine whether any association could be attributed to an identifiable mechanism.</p><p><strong>Study design: </strong>We retrospectively analyzed 132 adults who underwent their first MUD HCT for primary MF between 2000 and 2021 using the Japanese nationwide transplant registry, dichotomized at the median donor age of 41 years (younger, n = 65; older, n = 67). Engraftment, GVHD, non-relapse mortality (NRM) and relapse were analyzed by the Fine-Gray method, and overall survival (OS), disease-free survival (DFS) and GVHD-free, relapse-free survival (GRFS) by the Kaplan-Meier method. Multivariable models were adjusted for prespecified covariates and baseline imbalances. Missing data were handled by multiple imputation.</p><p><strong>Results: </strong>Donor age increased over the study period (r = 0.332, P < 0.001). Day-50 neutrophil engraftment was similar (89.2% vs 89.6%, P = 0.868), but after adjustment older donor age predicted slower neutrophil (hazard ratio [HR] 0.65, 95% CI 0.45-0.95, P = 0.027) and platelet (HR 0.41, 95% CI 0.23-0.72, P = 0.002) recovery; the nucleated cell dose of marrow declined with donor age and accounted for this association. Grade III-IV acute GVHD at day 100 was higher with older donors (15.1% vs 1.6%, P < 0.001; adjusted HR 13.73, 95% CI 1.87-100.76, P = 0.010), although events were few. Three-year NRM was 34.4% vs 21.4% (adjusted HR 1.76, 95% CI 0.91-3.40, P = 0.093) and 3-year relapse 35.4% vs 26.3% (adjusted HR 1.36, 95% CI 0.73-2.54, P = 0.329). Older donor age was associated with inferior 3-year OS (35.1% vs 62.4%; adjusted HR 2.07, 95% CI 1.19-3.62, P = 0.010), DFS (HR 1.73, 95% CI 1.04-2.90, P = 0.036) and GRFS (HR 1.86, 95% CI 1.17-2.96, P = 0.009).</p><p><strong>Conclusion: </strong>In MUD HCT for MF, older donor age was associated with slower engraftment, more severe acute GVHD and inferior survival. The engraftment findings were explained by the lower nucleated cell dose of marrow from older donors, but no mechanism could be identified for the survival difference, and residual confounding cannot be excluded. Donor age should therefore be regarded as an independent prognostic marker available at donor selection rather than a demonstrated causal determinant. In a steadily ageing donor registry, the magnitude of this association supports giving donor age explicit weight when equivalent HLA matches are available.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148146","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":"Cystatin C Based eGFR Identifies Clinically Significant Acute Kidney Injury Missed by Serum Creatinine in Pediatric Transplant-Associated Thrombotic Microangiopathy.","authors":"Taylor Fitch, Erin Frost, Tahsin Rajabali, Suhag Parikh, Muna Qayed, Adrianna Westbrook, Satheesh Chonat, Kirsten M Williams, Michelle L Schoettler","doi":"10.1016/j.jtct.2026.10.006","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.006","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138478","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 \"Reduced Cumulative Post-Transplant Cyclophosphamide Exposure is Associated with Increased Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation\".","authors":"Tomohiro Nagano, Takumi Kondo, Yoshinobu Maeda","doi":"10.1016/j.jtct.2026.10.008","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.008","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138548","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":"Preemptive and therapeutic donor lymphocyte infusion for acute leukemia or myelodysplastic syndromes: a real-world single-center study.","authors":"Luiz Frederico Bezerra Honorato Junior, Mariana Lorenzi Savioli, Andreza Feitoza Ribeiro, Andrea Kondo, Fabio Pires de Souza Santos, Mariana Nassif Kerbauy, Cinthya Correa da Silva, Guilherme Fleury Perini, Gabriele Zamperlini Netto, Juliana Folloni Fernandes, Jose Mauro Kutner, Nelson Hamerschlak, Leonardo Javier Arcuri","doi":"10.1016/j.jtct.2026.10.005","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.10.005","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Allogeneic hematopoietic cell transplantation (HCT) remains a potentially curative therapy for a broad range of hematologic malignancies. Early attempts to reduce graftversus-host disease (GVHD), particularly through in vitro T-cell depletion, underscored the central role of donor immune cells in disease control but also increased infectious complications and compromised the graft-versus-leukemia (GvL) effect. Donor lymphocyte infusion (DLI) is a strategy to enhance the GvL effect by adoptively transferring donor-derived immune effector cells. This single-center, retrospective study at Hospital Israelita Albert Einstein in São Paulo, Brazil, evaluated clinical outcomes among patients receiving preemptive or therapeutic DLI after HCT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We included patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or acute lymphoblastic leukemia (ALL) who received DLI after HCT between January 2010 and December 2025 for MRD+ or relapse. A formal comparison between preemptive and therapeutic DLI was not performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Forty-five patients were included, with a median age of 47 years and a median followup of 18 months. Of these, 34 received therapeutic DLI, and 11 received preemptive DLI. The mean initial dose was 5×106 CD3/kg for therapeutic DLI and 1×106 CD3/kg for preemptive DLI. Patients with MSD received 1×107 CD3/kg; URD, 5×106 CD3/kg; and Haplo, 1×106 CD3/kg. Seventeen patients were receiving concurrent immunosuppression at the time of DLI. Overall, 34 of 45 patients (76%) also received additional disease-directed pharmacologic therapy. The response rate (RR) after thefirst DLI dose was 67% (30 of 45), with 82% (9 of 11) in the preemptive group and 62% (21 of 34) in the therapeutic group, including 23 MRD-negative responses (51%). Progression-free survival (PFS) at 1 year was 73% (95% CI 51-100%) with preemptive therapy and 38% (24-58%) with therapeutic strategy (Figure 2). Overall survival rates were 73% (51-100%) and 51% (36-72%), respectively. One-year relapse rates were 18% (5-64%) for preemptive therapy and 53% (39-73%) for therapeutic therapy. Nonrelapse mortality was 9% for both groups (4-23%). All patients were free of active GVHD. The cumulative incidence of clinically significant GVHD (grade III-IV acute GVHD or moderate-to-severe chronic GVHD) was 9% (1-59%) with preemptive treatment and 18% (9-37%) with therapeutic treatment. Of these, 58% had steroidrefractory disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;In conclusion, our findings support the effectiveness of preemptive, MRD-based DLI strategies. However, the durability of response remains strongly influenced by underlying disease biology. Therapeutic DLI for overt relapse continues to yield suboptimal results, reinforcing the need for clinical trials testing combined approaches. The role of prophylactic DLI was not addressed in the current study and can only be reliably assessed in ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128667","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 Early Bloodstream Infections on Clinical Outcomes Following Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GVHD Prophylaxis.","authors":"Moazzam Shahzad, Muhammad Kashif Amin, Amna Bint I Munir, Shajadi Patan, Shah Rukh, Amir Reza Akbari, Aroog Khaliq, Laiba Yaseen, Muhammad Abdullah Humayun, Amna Zaheer, Vanessa Kennedy, Anson E Snow, Mehdi Hamadani, Joseph McGuirk, Muhammad Umair Mushtaq","doi":"10.1016/j.jtct.2026.07.004","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.07.004","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Bloodstream infections (BSIs) remain a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT), particularly during the post-transplant neutropenia and immune reconstitution phase. Notably, studies have identified high rates of BSI in the early post-transplant period with PTCy regimens, including single-center cohorts that have highlighted Candida, Enterococcus, and gram-negative rods (GNRs) as predominant pathogens. However, the broader clinical impact of pathogen-specific BSI on post-HCT outcomes in PTCy recipients remains incompletely defined. We aimed to study allo-HCT outcomes in patients who developed BSI in the first 100 days.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a retrospective, registry-based cohort analysis using dataset P-5242 from the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult patients who underwent allo-HCT with PTCy-based GVHD prophylaxis between 2009 and 2016 were included. Microbiologically confirmed BSIs within the first 100 days post-HCT were categorized by pathogen. Multivariable Cox proportional hazards models were used to evaluate associations between specific pathogens and acute GVHD (grade II-IV), chronic GVHD, time to neutrophil engraftment (ANC ≥ 500), overall survival (OS), and Non-relapse mortality (NRM). Adjusted covariates included patient age, gender, disease type, conditioning intensity, graft source, donor type, Hematopoietic Cell Transplantation-Comorbidity Index, and Karnofsky performance score.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 385 patients who developed BSI within the first 100 days post-transplant were included. The mean age was 50.0 years (SD 18.6), and 60.5% were male. 49.1% had acute myeloid leukemia (AML), 15.8% had acute lymphoblastic leukemia (ALL), 26.5% had myelodysplastic syndrome (MDS), and 8.6% had non-malignant diseases. Total body irradiation (TBI) was used in 56.4% patients, and only 5.7% received anti-thymocyte globulin. Graft sources were peripheral blood stem cells (PBSC) in 54.8%, bone marrow in 45.2%, and cord blood in 0.3%. 51.2% had a Karnofsky Performance Score of &lt;90, and 53.8% had an HCT-comorbidity index score&gt;3. In multivariable analysis, Candida infections and Enterococcus were associated with inferior survival (HR 3.369, 95% CI, p &lt; 0.001, and HR 1.497, 95% CI, p = 0.049, respectively). Non-Enterobacteriaceae gram-negative rod BSI was also independently associated with inferior non-relapse mortality (HR 2.198; 95% CI, p = 0.003).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This analysis demonstrates that early bloodstream infections significantly alter clinical outcomes in allogeneic hematopoietic stem cell transplant recipients receiving PTCy-based GVHD prophylaxis. Infections caused by Candida, Enterococcus species, and non-Enterobacteriaceae GNRs were associated with poorer survival. These findings highlight the importance of enhanced antimicrobial s","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128705","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":"Infused CD34+ cell dose predicts response to stem cell boost in children with poor graft function following allogeneic hematopoietic stem cell transplantation: a multicenter study from the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).","authors":"María Isabel Benítez-Carabante, Marina Ortiz-Palacios, Juan Antonio Carbonell-Asins, Sara Vinagre Enríquez, María Luz Uría-Oficialdegui, Yasmina Mozo Del Castillo, Iván López Torija, Luisa Sisinni, Blanca Molina, Mercedes Plaza Fornieles, Andrea Urtasun-Erburu, Carolina Fuentes Socorro, Marta García Culebras, María Trabazo Del Castillo, Jesús Fernández Sojo, Nerea Castillo-Flores, Laura Alonso García, Marta González-Vicent, Cristina Díaz-de-Heredia","doi":"10.1016/j.jtct.2026.09.049","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.09.049","url":null,"abstract":"<p><strong>Background: </strong>Poor graft function (PGF) is a severe and potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by persistent cytopenias despite adequate donor chimerism. Although CD34+ selected stem cell boost (CD34+SCB) has emerged as a promising treatment, evidence in pediatric patients remains limited, and the optimal CD34+ cell dose required to achieve complete hematologic recovery has not been established.</p><p><strong>Objectives: </strong>To evaluate outcomes of CD34+SCB in children with PGF, identify factors associated with hematologic recovery and survival, and determine the CD34+ cell dose required to achieve complete hematologic recovery with external validation.</p><p><strong>Methods: </strong>We conducted a national multicenter retrospective study. Pediatric patients (≤18 years) with severe PGF involving at least two hematopoietic lineages who received CD34+SCB from the original donor were included in the training cohort (n=42). Primary endpoint was complete response (CR). Secondary endpoints included overall response rate (ORR), overall survival (OS) and factors associated with CR and OS. The optimal CD34+ cell dose threshold predicting CR was identified using maximally selected rank statistics and externally validated with an independent cohort.</p><p><strong>Results: </strong>Median time from HSCT to PGF diagnosis was 89 days, and 88% of patients presented with trilineage cytopenia. The median infused CD34+ cell dose was 7.3 × 10⁶/kg. ORR and CR were 83.3% and 61.9%, respectively, with median time to CR of 43 days. With a median follow-up of 19.9 months, 2-year OS was 59.5%. Most deaths were due to infections and occurred in non-responders. In multivariable analysis, infused CD34+ cell dose was the only independent factor predictor of CR (HR 1.14, 95% CI 1.02-1.26; p=0.019). A threshold of 4.65 × 10⁶ CD34+ cells/kg significantly discriminated the probability of achieving CR in the training cohort (p=0.016) and was independently validated in the external cohort (p=0.013). Previous chronic graft-versus-host disease (GVHD) and haploidentical transplantation were independently associated with inferior OS. CD34+SCB demonstrated a favorable safety profile, with low incidences of de novo acute and chronic GVHD CONCLUSION: CD34+SCB is an effective and safe therapeutic strategy for pediatric PGF following HSCT, achieving high hematologic recovery rates with acceptable long-term survival. Infused CD34+ cell dose is the main determinant of complete hematologic recovery, and a minimum threshold may help optimize treatment outcomes. Further studies are warranted to refine risk-adapted approaches in this high-risk population.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115372","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":"CAR T‑Cell Therapy as a Bridging Strategy to Second Transplant in Relapsed B‑Cell ALL.","authors":"Vaibhav Agrawal, Haoyue Shan, Monzr Al Malki, Amandeep Salhotra, Ahmed Aribi, Paul Koller, Karamjeet Sandhu, Salman Otoukesh, Haris Ali, Hoda Pourhassan, Andrew Artz, Tamer Othman, Yazeed Samara, Len Farol, Anthony Stein, Ryotaro Nakamura, Guido Marcucci, Vinod Pullarkat, Stephen Forman, Ibrahim Aldoss","doi":"10.1016/j.jtct.2026.09.048","DOIUrl":"10.1016/j.jtct.2026.09.048","url":null,"abstract":"<p><p>A second allogeneic transplant (HSCT2) may offer cure for selected patients with acute lymphoblastic leukemia (ALL) relapsing after first transplant (HSCT1), however, outcomes have historically been poor, largely driven by high incidence of subsequent relapse. Chimeric antigen receptor (CAR) T‑cell therapy induces deep and durable remissions in relapsed/refractory (R/R) ALL, yet its role as a bridge to HSCT2 remains under studied. Consolidation with transplant after CAR-T therapy may enhance post‑HSCT2 disease control and improve outcomes. To compare HSCT2 outcomes according to bridging therapy strategies, with a particular focus on CAR T‑cell therapy versus non‑CAR bridging approaches. This is a single‑center retrospective analysis of adult patients with relapsed B‑cell ALL after a HSCT1 who subsequently underwent a HSCT2 in complete remission (CR) at City of Hope. Among 55 adults with relapsed B‑ALL who underwent HSCT2, the median age was 32, with a median of 4 prior lines of therapies. The median time from HSCT1 to relapse was 425 days, and over half of patients proceeded to HSCT2 in ≥CR3. Salvage therapy included CAR T‑cell therapy in 23 patients (42%), blinatumomab in 12 (22%), inotuzumab ozogamicin in 12 (22%), and other regimens in 8 (15%). Baseline patients and disease characteristics were not significantly different between those receiving CAR T and other salvage approaches. Patients receiving CAR T-cell therapy before HSCT2 had significantly improved 2-year progression free survival (PFS) (67.6% vs. 31.4%, p = .003) and overall survival (OS) (77.3% vs. 51.6%, p = .021) compared with other salvage therapies, respectively. Cumulative incidence of relapse was significantly lower in patients who received CAR T‑cell therapy before HSCT2 (p = .01), while non-relapse mortality was similar between the 2 groups (p = .43). In multivariable analysis, CAR T-cell therapy remained independently associated with superior PFS (HR: 0.26; 95% CI, 0.10 to 0.62; p < .001) and OS (HR: 0.33; 95% CI, 0.13 to 0.81; p = .026). A longer interval from HSCT1 to relapse (>475 days) also predicted improved OS (HR: 0.42; 95% CI, 0.18 to 0.96; p = .04), while older age showed a trend toward inferior OS (HR: 2.17; 95% CI, 0.97 to 4.89; p = .054). Our study supports CAR T-cell therapy as an effective bridging strategy to HSCT2 in selected patients with relapsed B-ALL, associated with improved post HSCT2 survival outcomes and reducing relapse. Careful optimization of patient selection and timing of transplant remains critical to maximize long-term outcomes.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115316","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}