Transplantation and Cellular Therapy最新文献

{"title":"The Association of HLA-E Ligand and NKG2 Receptor Variation With Relapse and Mortality After Haploidentical Related Donor Transplantation","authors":"Effie W. Petersdorf ,&nbsp;Caroline McKallor ,&nbsp;Mari Malkki ,&nbsp;Katherine Hsu ,&nbsp;Meilun He ,&nbsp;Stephen R. Spellman ,&nbsp;Theodore Gooley ,&nbsp;Philip Stevenson","doi":"10.1016/j.jtct.2025.01.004","DOIUrl":"10.1016/j.jtct.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Recurrence of blood malignancy is the major cause of mortality after hematopoietic cell transplantation. NKG2 receptor/HLA-E ligand complexes play a fundamental role in the surveillance and elimination of transformed cells but their role in the control of leukemia in transplantation is unknown.</div></div><div><h3>Objective</h3><div>We tested the hypothesis that gene variation of patient and/or donor HLA-E ligand and donor NKG2C-NKG2A receptors are associated with the risks of relapse and mortality (primary endpoints) and GVHD and non-relapse mortality (secondary endpoints) after haploidentical transplantation.</div></div><div><h3>Study Design</h3><div>We retrospectively defined donor NKG2 receptor haplotypes and patient HLA-E ligands in 1629 haploidentical related transplantations. HLA-E residue 107 was genotyped in patients and donors. Single nucleotide polymorphisms descriptive of NKG2C and NKG2A haplotypes were characterized in donors. Overall mortality, relapse, nonrelapse mortality and chronic GVHD were studied using Cox regression models. Acute GVHD was studied by logistic regression.</div></div><div><h3>Results</h3><div>The hazard of relapse for patients transplanted from NKG2C-del/del donors was 51% lower than that from wt/wt donors (hazard ratio, HR, .49 [95% CI, .26 to .89) contributing to a HR for mortality of .62 (95% CI, .38 to 1.02). The HR of mortality among patients transplanted from a donor with 2 vs. 0 copies of the NKG2A rs35909400-rs2734440-rs12824474 CCC haplotype was HR 2.28 (95% CI, 1.34 to 3.86). The HRs of mortality for ArgArg and ArgGly patients compared to GlyGly patients were 1.42 (95% CI, 1.11 to 1.82) and 1.43 (95% CI, 1.13 to 1.81), respectively. Hazard ratios for nonrelapse mortality for patients with ArgGly or ArgArg genotypes compared to patients with GlyGly genotype were HR 1.60 (95% CI, 1.06 to 2.41) and HR 1.79 (95% CI, 1.21 to 2.66), respectively. Assessment of donor receptor/patient ligand pairings showed that among Arg-positive patients, the HR of mortality from donors with any wt-CCC/CCC haplotype was HR 2.52 (95% CI, 1.45 to 4.38) relative to donors with any wt-non CCC/CCC haplotype.</div></div><div><h3>Conclusions</h3><div>The success of haploidentical transplantation may be defined by the cumulative effects of donor NKG2 receptor and patient HLA-E ligand polymorphisms. Patient HLA-E ligand and donor NKG2C-NKG2A receptor haplotypes shed new light on their role in the control of malignancy.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 137-156"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972276","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 Obesity on GVHD in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies","authors":"Valentina Ardila ,&nbsp;Hong Li ,&nbsp;Claudio Brunstein ,&nbsp;Matt Kalaycio ,&nbsp;Ronald Sobecks ,&nbsp;Craig S. Sauter ,&nbsp;Betty K. Hamilton","doi":"10.1016/j.jtct.2025.01.881","DOIUrl":"10.1016/j.jtct.2025.01.881","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between obesity and graft-versus-host disease (GVHD) has been studied in both preclinical and clinical studies with varying results.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the impact of obesity, as measured by body mass index (BMI), on the incidence, severity, and response to therapy of GVHD in a contemporary cohort.</div></div><div><h3>Study Design</h3><div>We conducted a retrospective study of patients undergoing allogeneic hematopoietic cell transplant (HCT) for acute myelogenous leukemia and myelodysplastic syndrome between January 2010 and December 2021 at the Cleveland Clinic. Incidence, grade, organ involvement, and response to therapy of acute and chronic GVHD were compared between patients with obesity (BMI ≥30) and without obesity. Secondary outcomes included relapse, nonrelapse mortality (NRM), and overall survival (OS).</div></div><div><h3>Results</h3><div>531 patients were identified, with a median follow-up of 19 months (range, 7-49). Mean (SD) BMI at time of HCT was 29.1 (6.3) kg/m². There was no significant difference in demographic and HCT characteristics between patients with obesity (N = 199) and without obesity (N = 332). Development of any acute (42% versus 43%) or chronic (29% versus 30%) GVHD was similar in patients with and without obesity. Patients with obesity were less likely to have gastrointestinal involvement from chronic GVHD (28% versus 48%, <em>P</em> = .01). Skin (64% versus 56%), mouth (45% versus 35%) and eye (35% versus 27%) involvements were higher in patients with obesity, although statistically not significant. There were no significant differences in OS, NRM, or relapse.</div></div><div><h3>Conclusion</h3><div>There were no significant differences in incidence of GVHD among patients with and without obesity. Additional studies are needed to further understand potential differences in organ involvement.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 178.e1-178.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012383","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":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(25)01028-0","DOIUrl":"10.1016/S2666-6367(25)01028-0","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A3"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511131","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":"Surgical Considerations in Tumor-Infiltrating Lymphocyte Therapy: Challenges and Opportunities","authors":"Amanda Kirane ,&nbsp;David Lee ,&nbsp;Charlotte Ariyan","doi":"10.1016/j.jtct.2024.11.015","DOIUrl":"10.1016/j.jtct.2024.11.015","url":null,"abstract":"<div><div>Adoptive T cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a promising personalized immunotherapy approach, spearheaded by Dr. Steven Rosenberg, targeting various cancer types. Despite initial challenges in TIL production, recent advancements have showcased its superiority to immune checkpoint blockade in metastatic melanoma, even after anti-PD-1 therapy failure. The expedited manufacturing process, now around 3 weeks, coupled with the US Food and Drug Administration approval of lifileucel in 2024, is poised to propel TIL therapy into mainstream oncology. This commentary delves into the critical surgical aspects of TIL harvesting, emphasizing the integral role of surgeons in ensuring optimal TIL quality, safety, and therapeutic effectiveness. By shedding light on these considerations, this article aims to guide and enhance collaborative efforts in advancing TIL therapy for patients facing limited treatment options.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S591-S598"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610672","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":"The Clinical TIL Experience in Melanoma: Past, Present, Future","authors":"James W. Smithy ,&nbsp;Adam J. Schoenfeld ,&nbsp;Allison Betof Warner","doi":"10.1016/j.jtct.2024.11.013","DOIUrl":"10.1016/j.jtct.2024.11.013","url":null,"abstract":"<div><div>The recent approval of lifileucel by the US Food and Drug Administration in February 2024 was the culmination of over 3 decades of research in adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) for unresectable melanoma. In this review, we highlight key historical data for TIL therapy in melanoma as well as ongoing efforts to improve its efficacy and applicability.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S626-S634"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610677","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":"Risk-Adapted Letermovir Prophylaxis Based on a Scoring System Predicting a Higher Burden of Cytomegalovirus Exposure After Allogeneic Hematopoietic Cell Transplantation","authors":"Shunto Kawamura ,&nbsp;Shin-ichiro Fujiwara ,&nbsp;Shun-ichi Kimura ,&nbsp;Junko Takeshita ,&nbsp;Hideki Nakasone ,&nbsp;Kazuki Yoshimura ,&nbsp;Yuya Nakata ,&nbsp;Takuto Ishikawa ,&nbsp;Akari Matsuoka ,&nbsp;Tomohiro Meno ,&nbsp;Yuhei Nakamura ,&nbsp;Masakatsu Kawamura ,&nbsp;Nozomu Yoshino ,&nbsp;Yukiko Misaki ,&nbsp;Ayumi Gomyo ,&nbsp;Machiko Kusuda ,&nbsp;Rui Murahashi ,&nbsp;Kento Umino ,&nbsp;Daisuke Minakata ,&nbsp;Masahiro Ashizawa ,&nbsp;Yoshinobu Kanda","doi":"10.1016/j.jtct.2025.01.883","DOIUrl":"10.1016/j.jtct.2025.01.883","url":null,"abstract":"<div><div>We previously reported that the area under the curve of log-transformed cytomegalovirus antigenemia (CMV-AUC) until 100 days after allogeneic hematopoietic cell transplantation (allo-HCT) was associated with an increased risk of non-relapse mortality. We applied a risk-adapted letermovir (LTV) prophylaxis strategy guided by a risk score that predicts a higher CMV-AUC. First, we retrospectively analyzed 278 allo-HCT recipients between 2007 and 2017 (Period 1). We scored risk factors for higher CMV-AUC by odds ratios: malignant lymphoma including adult T cell leukemia/lymphoma (1 point), an unrelated or haploidentical donor (1 point), and recipient/donor CMV serostatus (+/+; 2 points, +/-; 3 points). We have administered LTV to patients with a total score of ≥ 4 points. We then focused on 143 patients who underwent allo-HCT when we applied this strategy (Period 2). Forty patients (28%) in Period 2 received LTV prophylaxis. Two patients (5.4%) exhibited higher CMV-AUC among 37 patients in the higher-risk group (≥ 4 points). However, as many as 33% of the patients with 3 points in Period 2 experienced higher CMV-AUC. Notably, in the lower-risk patients of Period 2, 68% of patients who received systemic steroids for acute graft-versus-host-disease (GVHD) developed higher CMV-AUC. Our risk-adapted LTV prophylaxis strategy effectively prevented higher CMV-AUC in the higher-risk group and reduced the use of LTV. Additionally, including the use of systemic steroids for acute GVHD in this risk-adapted approach is preferable.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 184.e1-184.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012405","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":"The NKG2/HLA-E Axis Influence Outcomes of Haploidentical Transplantation","authors":"Lamberto Torralba-Raga ,&nbsp;Karl-Johan Malmberg","doi":"10.1016/j.jtct.2025.02.008","DOIUrl":"10.1016/j.jtct.2025.02.008","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 118-120"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511134","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":"Defining the Quality Attributes for Tumor-Infiltrating Lymphocyte Medicinal Products","authors":"Justin J. Lievense ,&nbsp;Cynthia Nijenhuis ,&nbsp;Inge Jedema ,&nbsp;Arendien Jonker-Hoogerkamp ,&nbsp;Justin T. Moyers ,&nbsp;Omid Hamid ,&nbsp;Jos H. Beijnen ,&nbsp;John B.A.G. Haanen ,&nbsp;Bastiaan Nuijen","doi":"10.1016/j.jtct.2024.04.015","DOIUrl":"10.1016/j.jtct.2024.04.015","url":null,"abstract":"<div><div>Tumor-infiltrating lymphocyte (TIL) medicinal products (MPs) show promise for treating solid tumors, especially metastatic melanoma, in the clinical trial setting. Through these studies, TIL developers have gained an immunological perspective into the mechanism of action (MoA) and infusion product characteristics that influence clinical response. However, to reach marketing authorization for any of the TIL MPs, it will be beneficial to gain a pharmaceutical (process) development perspective as well, from which control of the TIL MPs manufacturing process can be demonstrated and a suitable control strategy can be developed. To do this, a well-defined TIL MP must be established. Defining and optimizing MPs from a pharmaceutical perspective is done by identifying and improving product characteristics or quality attributes (QAs) thought to impact safety and efficacy. Through awareness of the QAs relevant to TIL MPs and considering them throughout pharmaceutical development, improvements and changes can be validated. This approach to pharmaceutical development is part of the quality-by-design workflow, of which this review tackles the first steps. Here, the QAs are structured within a quality target product profile (QTPP), and the corresponding regulatory expectations are considered, spanning quantity, identity, purity, microbiological assays, and biological activity. Based on the regulatory expectations and available literature, the (critical) QAs and points of consideration are proposed when developing TIL MPs. The active pharmaceutical ingredient of the TIL MP is defined as the CD45+CD3+ cells. By analyzing identity attributes correlated to clinical efficacy, four broadly applicable <em>in vivo</em> functionalities associated with TIL MPs MoA and clinical effectiveness are described: tumor recognition, cytotoxic capacity, tumor homing, and persistence. How these <em>in vivo</em> functionalities are quantified in potency assays and the limitations of their methods/readouts are also discussed. The QTPP is a foundation for developing a robust, substantiated control strategy for regulatory approval and increasing patient access. Harmonizing TIL MP development under a unified QTPP applicable in different settings could also facilitate comparisons and, therefore, the development of safer and more efficacious TIL MP variations.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S610-S625"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610676","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":"Tumor-Infiltrating Lymphocyte Therapy for Melanoma and Other Solid Tumors: Looking Back, Yet Moving Forward","authors":"Alexander N. Shoushtari ,&nbsp;Daniel J. Powell","doi":"10.1016/j.jtct.2024.11.017","DOIUrl":"10.1016/j.jtct.2024.11.017","url":null,"abstract":"<div><div>Lifileucel, the first solid tumor adoptive tumor infiltrating lymphocyte (TIL) therapy product to receive regulatory approval in advanced melanoma, represents a critical achievement in the pursuit of improving outcomes using cellular therapies in patients with solid tumors. This review traces the development of adoptive TIL therapy from the initial human studies in melanoma, through recent advances in studies of other solid tumors, and previews ongoing and future areas for preclinical and clinical advances to improve upon this novel therapeutic strategy.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S581-S590"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610671","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":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(25)01017-6","DOIUrl":"10.1016/S2666-6367(25)01017-6","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A3"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610678","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}