Transplantation and Cellular Therapy最新文献

{"title":"Role of Donor Cytomegalovirus Serostatus in Cytomegalovirus-Seronegative Recipients of Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Prophylaxis.","authors":"Rohtesh S Mehta, Yosra M Aljawai, Taha Al-Juhaishi, Jennifer Saultz, Filippo Milano, Jennifer A Kanakry, Christopher G Kanakry, Aleksandr Lazaryan","doi":"10.1016/j.jtct.2025.05.005","DOIUrl":"10.1016/j.jtct.2025.05.005","url":null,"abstract":"<p><p>While donor age significantly impacts allogeneic hematopoietic cell transplantation (HCT) outcomes, the effect of donor cytomegalovirus (CMV) serostatus, particularly in CMV-seronegative recipients, remains a critical consideration. Donor CMV seropositivity is linked to increased CMV viremia and non-relapse mortality (NRM) in these recipients. Given the limited scope of novel antiviral prophylaxis drugs, eg, letermovir solely for CMV-seropositive recipients and the association of post-transplant cyclophosphamide (PTCy) with increased CMV reactivation, this study investigates the impact of donor CMV serostatus on outcomes in CMV-seronegative acute myeloid leukemia (AML) patients undergoing HLA-matched or mismatched unrelated donor HCT with PTCy. We retrospectively analyzed data from the Center for International Blood and Marrow Transplant Research, including adult CMV-seronegative AML patients who underwent unrelated donor HCT with PTCy between 2017 and 2021. Primary outcome was overall survival (OS). Secondary outcomes included relapse, NRM, and acute/chronic graft-versus-host disease. Donor age was dichotomized at ≤32 and >32 years. Multivariable Cox proportional hazards models, stratified by donor age, and Restricted Mean Survival Time (RMST) and Restricted Mean Time Lost (RMTL) analyses were performed. Of 408 CMV-seronegative recipients, 127 received transplants from CMV-seropositive donors. Baseline characteristics were well-balanced between groups. Multivariable analysis demonstrated that recipients of CMV-seropositive donors had a significantly higher hazard of mortality (hazard ratios [HR] 1.51, 95% confidence interval [CI] 1.07 to 2.14, P = .019). Donor age and donor type did not significantly impact OS in this CMV seronegative patient population. RMST analysis showed that recipients with CMV-seronegative donors lived on average 2.95 months longer (P = .045), while RMTL ratio was 1.34 (P = .037), indicating that recipients of CMV-seropositive donors experienced a 34% higher risk of loss of survival time. The difference in OS was primarily driven by a trend toward increased relapse risk in the CMV-seropositive donor group (HR 1.42, 95% CI: 0.95 to 2.08, P = .06) rather than NRM (HR 1.19, 95% CI: 0.66 to 2.13, P = .56). In CMV-seronegative adult AML patients undergoing unrelated donor HCT with PTCy, CMV-seropositive donors are associated with worse OS than CMV-seronegative donors, likely linked to higher relapse risk. These findings underscore the importance of considering donor CMV serostatus in donor selection for CMV-seronegative recipients undergoing HCT with PTCy. Further investigation is necessary to optimize donor selection strategies and improve outcomes in this patient population.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086682","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":"Comparison of Regimens Used for Allogeneic Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease.","authors":"Daniel Prior, Jingchen Liang, Yanhong Deng, Niketa Shah, Aron Flagg, Lakshmanan Krishnamurti","doi":"10.1016/j.jtct.2025.05.004","DOIUrl":"10.1016/j.jtct.2025.05.004","url":null,"abstract":"<p><p>Prior analyses have reported on the impact of different donor types and conditioning regimen intensities on outcomes for patients with sickle cell disease (SCD) who undergo hematopoietic cell transplantation (HCT), and demonstrated superior outcomes using an HLA-matched related donor (MRD). However, the impact of conditioning regimen intensity on outcomes remains unclear, with conflicting findings across studies. In addition, the lack of data on comparative outcomes of different approaches to conditioning and graft-versus-host disease (GVHD) prophylaxis for allogeneic HCT for SCD remains a gap in the field. We compared outcomes for SCD patients who have received HLA-matched related donor (MRD) HCT for SCD using different HCT regimens. We examined de-identified records of MRD HCT for SCD on patients transplanted between 1991 and 2022 in the United States and submitted to the CIBMTR. We compared the most common transplant regimens in the registry, which included TBI 300/400 cGy + sirolimus + anti-thymocyte globulin (ATG)/alemtuzumab described by Hsieh et al; Busulfan/Fludarabine + CNI/methotrexate (MTX) + ATG/alemtuzumab as described by Krishnamurti et al.; Fludarabine/Melphalan + CNI/MTX + ATG/alemtuzumab as described by King et al.; and Busulfan/Cyclophosphamide (CY) + CNI /MTX/prednisone + ATG/alemtuzumab as described by Walters et al. For pediatric MRD HCT, EFS rates were highest with the Krishnamurti et al. (3-year EFS 94%, 95% CI 88, 100) and lowest with the Hsieh et al. regimen (3-year EFS 57%, 95% CI 25, 100, p<0.001). Rates of chronic GVHD were lowest in the Hsieh et al. cohort (3-year rate 0%) and highest in the King et al. cohort (3-year rate 20.4%, 95% CI 13.2, 28.8, p=0.040). For adult MRD HCT, EFS rates were similar between the Hsieh et al. and Krishnamurti et al. regimens, while cGVHD was significantly lower in the Hsieh et al. cohort. These real-world data have the potential to inform shared decision-making in MRD HCT for SCD. Pediatric patients had the highest EFS rates using myeloablative conditioning regimens, while non-myeloablative conditioning resulted in the lowest EFS rates. Adult patients had similar event-free survival using myeloablative and non-myeloablative conditioning regimens, with less GVHD following non-myeloablative regimens.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086553","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":"Bloodstream Infections Due to Multidrug-Resistant Gram-Negative Organisms in Hematopoietic Stem Cell Transplant Recipients: A Multicenter Case-Control Study in a High-Prevalence Area.","authors":"Panagiota Palla, Ippokratis Konstantinidis, Zoi Boussiou, Maria Lagkadinou, Ioannis Tsonis, Maria Stamouli, Anna Paisiou, Panagiotis Oikonomopoulos, Maria Arapaki, Markos Marangos, Alexandros Spyridonidis, Dimitrios Karakasis, Maria Angelopoulou, Anastasia Pouli, Eugenios Goussetis, Panagiotis Tsirigotis, Damianos Sotiropoulos, Nikolaos V Sipsas, Maria N Gamaletsou","doi":"10.1016/j.jtct.2025.05.007","DOIUrl":"10.1016/j.jtct.2025.05.007","url":null,"abstract":"<p><strong>Background: </strong>Over the last decade, an alarming increase in multidrug-resistant gram-negative (MDR-GN) pathogens has been recorded at hematopoietic stem cell transplant (HSCT) centers around the world. Infections caused by MDR-GN bacteria not only lead to treatment failure and longer hospital stays but also result in high morbidity and mortality rates.</p><p><strong>Objective: </strong>To examine the incidence, risk factors, and outcomes of MDR-GN bacteremia among HSCT recipients in an area of high antimicrobial resistance.</p><p><strong>Study design: </strong>Patients with bacteremia from 7 Greek HSCT centers were prospectively enrolled and followed up for 12 months. We compared patients with MDR-GN bacteremia to those with non-MDR-GN bacteremia, gram-positive (GP) bacteremia and matched controls without bacteremia in terms of demographics, clinical features, microbiology, and outcomes.</p><p><strong>Results: </strong>In 523 HSCTs performed, we identified 142 episodes of bacteremia due to MDR-GN (38 patients), non-MDR-GN (37 patients), and GP pathogens (67 patients). The overall incidence of MDR-GN bacteremia was 1.4 per 1000 patient-days (95% confidence interval, 1.0-1.9), ranging from 0.0 to 2.9/1000 patient-days across participating centers (P = .01). When comparing patients with MDR-GN bacteremia to those with bacteremia caused by other organisms, in multivariate analysis, age and allogeneic HSCT were independent risk factors for MDR-GN bacteremia. The 12-month mortality rates were 34.5% in bacteremic patients, 60.5% for patients with MDR-GN, 32.4% with non-MDR-GN, and 20.9% with GP bacteremia (P < .001). MDR-GN bacteremia, relapse of the underlying disease, and GVHD were independent risk factors for death.</p><p><strong>Conclusions: </strong>These findings highlight the importance of implementing rigorous infection control measures, in HSCT centers located in areas with high prevalence of antimicrobial resistance.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086531","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":"Busulfan Once Versus Four Times Daily: Impact on Pharmacokinetics, Organ Toxicities and Survival After Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Claire Seydoux, Jakob R Passweg, Dominik Heim, Joerg Halter, Katharina M Rentsch, Michael Medinger","doi":"10.1016/j.jtct.2025.04.019","DOIUrl":"10.1016/j.jtct.2025.04.019","url":null,"abstract":"<p><p>Therapeutic drug monitoring of busulfan (Bu) used as conditioning for allogeneic stem cell transplantation (allo-HSCT) is recommended as pharmacokinetics (PK) display variability. Since 2019, we give Bu 1x/d (Bu-Q24) instead of 4x/d (Bu-Q6) for practical convenience, despite limited studies evaluating the best way of application. Our aim was to analyze the correlation between Bu administration (Bu-Q6 versus Bu-Q24), Bu-PK and clinical outcome in adult patients receiving Bu as conditioning regimen for allo-HSCT. This was a retrospective study of 256 adult patients receiving a myeloablative chemotherapeutic regimen containing Bu to treat hematological malignancies. The population was separated into 2 groups according to Bu administration, namely Bu-Q6 and Bu-Q24. A total of 133 patients received Bu-Q6 and 123 Bu-Q24. Bu-Q6 patients were more commonly treated with cyclophosphamide and Bu-Q24 with fludarabine. Bu-Q6 showed lower cumulative area-under-the-curve (AUC) values than Bu-Q24 (63.78 mg*h/L in Bu-Q6 and 70.12 mg*h/L in Bu-Q24, P = .06). Only 44% of the patients fell within the 1st AUC FDA target range in Bu-Q6 versus 62% in Bu-Q24 (P < .01). Overall, Bu-Q24 appeared to be superior to Bu-Q6 for most outcomes, showing lower incidence of toxicity grade ≥ II (78% versus 90%, P = .02), with less uro-renal (14% in Bu-Q24 versus 26% in Bu-Q6; P = .02), pulmonary (2% versus 8%, P = .05) and gastro-intestinal toxicities (10% versus 17%, P < .01). Patient receiving Bu-Q24 had fewer infections (51% versus 65%; P = .04), particularly bacterial (33% versus 47%, P = .03) and fungal infections (10% versus 20%; P = .03). At 2 yr, Bu-Q24 tended to have lower treatment-related mortality (TRM) (5% versus 10%, P = .13), relapse rate (37% versus 42%, P = .55) and incidence of acute and chronic graft-versus-host-disease (24% versus 28%; 32% versus 36%, respectively). The overall survival (OS) was 81% (95% CI 74% to 89%) in Bu-Q24 and 69% (95% CI 62% to 77%, P = .03) in Bu-Q6. The only benefit of Bu-Q6 was mucositis grade ≥ III, with an incidence of 36% versus 60% in Bu-Q24 (P < .01). Patients with a cumulative AUC < 59.11 mg*h/L had the lowest TRM, without impact on the OS. Bu clearance was largely influenced by BMI and age > 60 yr. Bu administered once a day shows benefit both in the short and long term compared to Bu administered 4 times a day, but data are heterogeneus, Bu-Q24 being more commonly associated with use of fludarabine, Bu-Q6 with use of cyclophosphamide in this study.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080592","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":"Health and Economic Impact of Vein-to-Vein Time in CAR T-Cell Therapy in the Second-Line Treatment of Relapsed/Refractory Large B-Cell Lymphoma: A US Cost-Effectiveness Analysis.","authors":"Olalekan O Oluwole, Markqayne D Ray, Hanxiao Ma, Rishika Sharma, Anik R Patel, Nathaniel Smith","doi":"10.1016/j.jtct.2025.05.002","DOIUrl":"10.1016/j.jtct.2025.05.002","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Chimeric antigen receptor T-cell (CAR T) therapies are approved in the United States (US) for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). In the CAR T treatment process, a short vein-to-vein time (V2VT) is critical to minimize the likelihood of deterioration from aggressive disease while waiting for infusion. This study evaluated the impact of V2VT on survival and economic outcomes for R/R second-line (2L) axicabtagene ciloleucel (axi-cel) versus lisocabtagene maraleucel (liso-cel) treatment of patients with LBCL in the US. An economic model was developed to evaluate the cost-effectiveness of 2L axi-cel versus liso-cel in patients with R/R LBCL over a 50-yr time horizon from a US third-party payer perspective. The model was comprised of: (1) a decision tree to account for V2VT, and (2) a 3-state partitioned survival model that captured health state transitions. Transition between health states were based on progression-free survival (PFS) and overall survival (OS) data stratified based on long (≥36 d) versus short (&lt;36 d) V2VT. The proportion of axi-cel patients with short and long V2VT was 94% and 6%, respectively, while that for liso-cel was 50% each. Survival data were sourced from the pivotal ZUMA-7 trial and varied for short and long V2VT, where V2VT-specific OS and PFS data were based on reported hazard ratios (HRs). Inputs for healthcare resource utilization, adverse events (AEs), costs, and utilities were sourced from published data or based on assumptions. The model estimated quality-adjusted life years (QALYs), total costs (in 2023 US dollars, $), the incremental cost-effectiveness ratio (ICER), and the net monetary benefit (NMB) at a willingness-to-pay threshold (WTP) of $150,000. Sensitivity and scenario analyses were conducted. Treatment with 2L axi-cel resulted in improved health outcomes compared with 2L liso-cel (incremental QALYs of 0.56) as well as reduced total costs (cost savings of $13,156). Under base case assumptions, 2L axi-cel dominated liso-cel (more effective and less costly) with an NMB of $96,407 for a WTP of $150,000. Key model drivers from one-way sensitivity analyses included OS HRs for short versus long V2VT, axi-cel acquisition costs, and the proportion of patients receiving third-line (3L) treatment. 2L axi-cel was always cost-effective compared with 2L liso-cel in probabilistic sensitivity analyses at a willingness-to-pay threshold of $50,000 per QALY, and 2L axi-cel is cost-saving compared with 2L liso-cel in 88% of the probabilistic sensitivity analysis runs. Results from scenario analyses where AE rates were varied, AEs were individually costed, and where 3L bispecific antibodies were excluded were consistent with base case results. 2L treatment with axi-cel was more effective and less costly compared with liso-cel in patients with LBCL in the US. These findings suggest that reduced V2VT was associated with improved clinical and economic outcomes, and highlight the importan","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080561","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":"Multicenter Study on Caregiver Experiences in Pediatric Hematopoietic Stem Cell Transplantation: Part II. Treatment Challenges, Communication Barriers, and Caregiver-Driven Approaches to Mitigation.","authors":"Rachel Phelan, Seth Rotz, Christopher E Dandoy, Jeffery J Auletta, Priscila Badia, Neel S Bhatt, Sheri A Ballard, Robyn Blacken, Nancy M Daraiseh, Catherine Desmond, Chloe Dunseath, Preston Epling, Laura Flesch, John Huber, Kari Jenssen, Malika Kapadia, Georgia Kent, Anna Klunk, Katilyn Kusnier, Leslie Lehmann, Nicole Liberio, Steffani Maier, Kasiani C Myers, Gabby O'Connor, Ahna Pai, Sarah Tarquini, Taylor J Fitch, David Hartley","doi":"10.1016/j.jtct.2025.04.012","DOIUrl":"10.1016/j.jtct.2025.04.012","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation (HSCT) is a life-saving yet complex treatment for pediatric patients that introduces significant physical, emotional, and logistical challenges for caregivers. This multicenter, prospective qualitative longitudinal study explored caregiver experiences across 4 time points: pre-transplant (n = 47), 30 d post-transplant (n = 43), 100 d post-transplant (n=34), and 6 months post-transplant (n=26). Forty-nine caregivers participated in semi-structured interviews, which were transcribed and thematically analyzed. This manuscript encompasses the following themes that emerged from the interviews: treatment-related side effects and complications, communication gaps, and the impact of the COVID-19 pandemic. Caregiver priorities evolved over time, shifting from managing acute complications such as pain, infections, mucositis, and medication administration to addressing longer-term concerns like developmental delays, nutritional rehabilitation, and psychosocial adaptation. Caregivers reported challenges such as information overload, inconsistent messaging, and limited preparation for transitions in care. They employed various strategies to cope, including advocacy, peer support, and the use of healthcare team resources. These findings highlight the importance of stage-specific, tailored interventions to support caregivers throughout the HSCT journey. Clear communication, accessible education, and coordinated multidisciplinary care are essential to fostering caregiver resilience and improving patient and family-centered outcomes.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987734","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":"Ruxolitinib in the Treatment of Acute Corticosteroid-Refractory Graft-Versus-Host Disease: A Scoping Review.","authors":"Maria Augusta Schramm do Nascimento, Solimar Ribeiro Carlete Filho, Mariana Daga Miranda, Antonio Eduardo Matoso Mendes, Gisele de Paula E Silva Carneiro Mendes de Souza, Helena Hiemisch Lobo Borba","doi":"10.1016/j.jtct.2025.04.018","DOIUrl":"10.1016/j.jtct.2025.04.018","url":null,"abstract":"<p><strong>Background: </strong>Graft-versus-Host Disease (GVHD) is a common complication following allogeneic hematopoietic stem cell transplantation (HSCT) and is considered one of the leading causes of post-transplant morbidity and mortality. Acute GVHD (aGVHD) primarily affects the skin, gastrointestinal tract, and liver. Despite advances in immunoprophylaxis, 20% to 80% of patients develop aGVHD, of whom only 60% respond to first-line treatment (e.g., methylprednisolone). Ruxolitinib, a selective inhibitor of Janus Kinase (JAK) 1 and 2, has been proposed as a treatment option following failure of first-line therapy.</p><p><strong>Objective: </strong>The present study aims to map the current evidence regarding the use of ruxolitinib in the treatment of glucocorticoid-refractory aGVHD in patients with hematologic diseases undergoing allogeneic HSCT.</p><p><strong>Study design: </strong>We performed a scoping review in accordance with the Joanna Briggs Institute guidelines. Systematic searches were performed in the PubMed and Scopus databases in December 2024, with no restrictions on year or language. Two independent reviewers carried out article selection and data extraction.</p><p><strong>Results: </strong>A total of 1162 studies were screened, with 13 matching the inclusion criteria. The articles were published between 2016 and 2024 and originated from developed countries, with the majority from China (33.8%) and Germany (23.1%), being predominantly retrospective cohort studies (38.5%) and case reports or case series (38.5%). The main adverse effects reported included infections, viral reactivation, and pancytopenia. The overall response rates were 65.0% for combination therapy and 67.4% in comparison with other therapies. All patients who received monotherapy achieved a complete or partial response to treatment, however, the studies involved small sample sizes, limiting the ability to extrapolate these findings.</p><p><strong>Conclusions: </strong>Ruxolitinib demonstrates therapeutic potential in this context; however, higher-level primary studies, such as randomized controlled trials, are necessary to achieve more robust conclusions.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016016","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":"Selective H2-O Tissue Expression Reduces Risk for Graft-versus-Host Disease in an In Vivo Transplantation Model.","authors":"J Zeun, A L Bernhardt, S Neubeck, V Lang, K Korn, L Nagel, T Kunert, S Brey, I Atreya, L Denzin, T Bäuerle, K Hildner, M Büttner-Herold, T Winkler, A Mackensen, H Reimann, A N Kremer","doi":"10.1016/j.jtct.2025.04.022","DOIUrl":"10.1016/j.jtct.2025.04.022","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic stem cell transplantation (aSCT) is frequently used to treat patients with hematologic malignancies. The therapeutic effect relies mainly on the graft-versus-leukemia (GVL) effect, in which donor T cells eliminate residual malignant cells. Unfortunately, the beneficial GVL effect is often accompanied by detrimental graft-versus-host disease (GVHD). A successful separation of both effects could not yet be achieved. In previous work, we identified 2 groups of HLA-class II restricted antigens depending on their behavior towards HLA-DM. DM-resistant antigens are presented in the presence of HLA-DM, whereas presentation of DM-sensitive antigens relies on the inhibitory molecule HLA-DO. Due to the unique expression pattern of HLA-DO, DM-sensitive antigens cannot be presented efficiently by non-hematopoietic cells even under inflammatory conditions. This suggests that CD4⁺ T cells directed against DM-sensitive antigens may be able to separate GVL from GVHD.</p><p><strong>Objective: </strong>In this study, we wanted to demonstrate convincingly that HLA-DO expression strongly influences the severity of GVHD in allogeneic stem cell transplantation.</p><p><strong>Methods: </strong>We generated a modified CD4 donor lymphocyte infusion (DLI) depleted of CD4⁺ T cells directed against DM-resistant antigens to address its potential to induce GVHD in an in vivo major histocompatibility complex (MHC) mismatch transplantation model dependent on selective tissue expression of H2-O using H2-O wildtype, knockout, and transgenic recipients.</p><p><strong>Results: </strong>Intriguingly, we could demonstrate that our modified CD4 DLI targeting DM-sensitive antigens induced only mild GVHD in wildtype recipients with endogenous selective H2-O expression and none in H2-O knockouts while assessing the immunogenic potential of DM-sensitive antigens in H2-O transgenic recipients.</p><p><strong>Conclusion: </strong>The results of the present work provide evidence that DM-resistant antigens are main targets of GVHD and addressing DM-sensitive antigens might be a promising tool to improve outcome after aSCT by separating GVL from GVHD.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048132","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 Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Cell Transplantation on the Relapse of Acute Leukemia.","authors":"Hyunkyung Park, Je-Hwan Lee, Heungsup Sung, Jung-Hee Lee, Han-Seung Park, Eun-Ji Choi, Kyoo-Hyung Lee, Sung-Han Kim, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Ji Min Woo, Hyeran Kang, Yunsuk Choi","doi":"10.1016/j.jtct.2025.04.021","DOIUrl":"10.1016/j.jtct.2025.04.021","url":null,"abstract":"<p><strong>Background: </strong>Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic cell transplantation (HCT) is a significant complication; however, its impact on relapse remains controversial.</p><p><strong>Objectives: </strong>This study aimed to evaluate the clinical impact of CMV reactivation on relapse and survival after HCT in patients with acute leukemia.</p><p><strong>Study design: </strong>We conducted a retrospective analysis of 1258 patients diagnosed with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) who underwent their first HCT between 2000 and 2020.</p><p><strong>Results: </strong>Our cohort included 871 patients with AML and 387 patients with ALL. Among all patients, 751 (61.6%) experienced CMV reactivation within one year post-HCT. CMV reactivation was associated with HCT from unrelated donors, anti-thymocyte globulin use, and the occurrence of acute graft-versus-host disease. Notably, CMV reactivation was associated with a lower risk of relapse (HR, 0.713; P = .001) and improved event-free survival (HR, 0.743; P = .001) in both AML and ALL patients. However, there was no significant difference in non-relapse mortality or overall survival according to CMV reactivation.</p><p><strong>Conclusion: </strong>These results suggest that CMV reactivation may prevent post-HCT relapse and enhance event-free survival in AML and ALL patients. Therefore, a CMV prophylaxis strategy is warranted to establish a safe range of CMV reactivation titers that can yield beneficial effects.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036411","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":"Allele and Haplotype Frequencies in High-Resolution Typing of Human Leukocyte Antigen -A, -B, -C, -DRB1, -DQB1 and -DPB1 in Thai Voluntary Stem Cell Donors.","authors":"Sriprapai Khanuntong, Tamonwan Tupmongkol, Sirilak Phiancharoen, Apiwat Tiyapan, Pawinee Kupatawintu, Dootchai Chaiwanichsiri, Martin Maiers, Pimol Chiewsilp","doi":"10.1016/j.jtct.2025.04.014","DOIUrl":"10.1016/j.jtct.2025.04.014","url":null,"abstract":"<p><p>The HLA allele and haplotype frequencies were calculated from 110,007 voluntary donors with HLA high-resolution typing and 263,542 voluntary donors with medium to high-resolution typing. This is the first study of a large samples with high-resolution HLA typing in Thai population. The frequencies of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles and haplotypes were calculated from typing by next generation sequencing (NGS). A total number of G groups for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 were 44, 83, 38, 42, 16 and 39, respectively. A total number of 2-field single allele for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 were 142, 196, 122, 122, 71, and 124, respectively. The variety of each HLA alleles in the Thais ranging from 1.86% to 5.58% of the total alleles in IMGT/HLA database. The frequencies of allele following common, intermediate and well-documented (CIWD) groups for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 were 104, 155, 87, 98, 48 and 96, respectively. The alleles with frequency greater than 5% were A*02:03, A*11:01, A*33:03, A*02:07, A*24:02, A*24:07, B*46:01, B*15:02, B*44:03, C*01:02, C*07:02, C*03:04, C*08:01, DRB1*12:02, DRB1*14:54 and DQB1*03:03. The haplotypes with frequency greater than 10% were A*33:03∼C*03:02∼B*58:01∼DRB1*03:01∼DQB1*02:01, A*02:07∼C*01:02∼B*46:01∼DRB1*09:01∼DQB1*03:03,A*33:03∼C*07:01:01G∼B*44:03∼DRB1*07:01∼DQB1*02:01:01G and A*11:01∼C*08:01∼ B*15:02∼DRB1*12:02∼ DQB1*03:01. These findings enable the registry to predict the opportunity to find good matched organ and stem cell donors for the patient with rare HLA typing.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983522","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}