Cell Transplantation最新文献

{"title":"Correlation of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes in Total Pancreatectomy With Islet Autotransplantation.","authors":"Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin","doi":"10.1177/09636897251317048","DOIUrl":"10.1177/09636897251317048","url":null,"abstract":"<p><p>This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including alcoholic, hereditary, idiopathic, Oddi dysfunction, and pancreatic divisum compared to healthy controls. The overall expression of LAMA5 positively correlated with expression of the ECM proteins pan-laminin (<i>R</i> = 0.63, <i>P</i> < 0.001), collagen IV (<i>R</i> = 0.67, <i>P</i> < 0.001), and Perlecan (<i>R</i> = 0.71, <i>P</i> < 0.001). Increased LAMA5 expression was observed within islet endothelial vascular tissue and the peri-islet basal membrane. Increased LAMA5 expression in the pancreas correlated with poor islet isolation yield and posttransplant islet function after 3 months. Increased endothelial expression of LAMA5 and ECM proteins is indicative of progressive damage to the pancreas and correlates with poor graft function after TPIAT.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251317048"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of human iPSC-derived white, beige, and brown adipocytes for metabolic disease modeling and transplantation therapy.","authors":"Yamato Keidai, Junji Fujikura, Daisuke Yabe","doi":"10.1177/09636897251346599","DOIUrl":"10.1177/09636897251346599","url":null,"abstract":"<p><p>Adipocyte dysfunction plays a critical role in the pathogenesis of metabolic diseases, including type 2 diabetes (T2D). Human induced pluripotent stem cells (hiPSCs) offer a powerful platform for generating white, beige, and brown adipocytes, supporting both disease modeling and therapeutic research. This review provides a comprehensive summary of current differentiation methods to produce three functionally mature adipocyte types from pluripotent stem cells (PSCs), including forced gene expression techniques, developmental biology-inspired approaches, and advanced three-dimensional (3D) culture systems that enhance cellular maturity and functional relevance. PSC-derived white adipocytes contribute to modeling adipocyte dysfunction not only in conditions such as insulin resistance, lipodystrophy, and premature aging but also in more complex metabolic diseases, including T2D, facilitating the investigation of disease mechanisms and the identification of novel therapeutic targets. In addition, iPSC-based models provide a robust platform for exploring genetic regulation by genome-wide association studies (GWAS)-identified variants through population genetics. This review also evaluates the therapeutic potential of iPSC-derived white, beige, and brown adipocytes in cell transplantation therapy for metabolic diseases, with a focus on engraftment potential and metabolic improvement. Enhancing the maturity and subtype specificity of PSC-derived adipocytes is expected to accelerate the development of personalized medicine and innovative therapeutic strategies for metabolic diseases.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251346599"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Threefold IPSS-M reclassification outperforms original stratification in predicting post-transplant outcomes for MDS patients.","authors":"Hongru Chen, Shan Jiang, Ruowen Wei, Ao Zhang, Xiena Cao, Wei Shi, Linghui Xia","doi":"10.1177/09636897251348406","DOIUrl":"10.1177/09636897251348406","url":null,"abstract":"<p><p>The predictive performance of the Molecular International Prognostic Scoring System (IPSS-M) for high-risk myelodysplastic syndromes (MDS) patients undergoing transplantation remains uncertain. We retrospectively analyzed 86 MDS patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center from 2016 to 2023. According to IPSS-M, patients were classified as Low (<i>n</i> = 3), Moderate-Low (<i>n</i> = 9), Moderate-High (<i>n</i> = 15), High (<i>n</i> = 28), and Very-High risk (<i>n</i> = 31). The IPSS-M did not demonstrate good prognostic accuracy for overall survival (OS) (<i>P</i> = 0.227) and disease-free survival (DFS) (<i>P</i> = 0.095) in these 86 patients. We then divided the patients into three groups based on their IPSS-M scores: IPSS-M < 0.56 (<i>n</i> = 28), IPSS-M 0.56-1.75 (<i>n</i> = 30), and IPSS-M>1.75 (<i>n</i> = 28). There was a significant difference in the long-term OS (<i>P</i> = 0.010) and DFS among the three groups (<i>P</i> < 0.001). This indicates that, based on the original IPSS-M scores, we may be able to find a more precise risk stratification for high-risk MDS patients undergoing allo-HSCT. Compared with TP53 wild-type and TP53 monoallelic mutations, TP53 biallelic mutations have a significant negative impact on OS and DFS (<i>P</i> = 0.016, <i>P</i> = 0.006). It is crucial to identify TP53 allelic status at diagnosis to distinguish these patients and determine the need for early involvement in clinical trials.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251348406"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplantation of Wild-Type Hematopoietic Stem and Progenitor Cells Improves Disease Phenotypes in a Mucopolysaccharidosis IIIC Mouse Model.","authors":"Rafael A Badell-Grau, Kasra Pakravesh, Kevin Eric Thai, Frankie Son, Rola Chen, Joseph Rainaldi, Kalvin Duong, Pauline Losay, Anusha Sivakumar, Veenita Khare, Alexis N Corl, Rushil Pithia, Christine Tran, Jefferey D Esko, Stephanie Cherqui","doi":"10.1177/09636897251323966","DOIUrl":"10.1177/09636897251323966","url":null,"abstract":"<p><p>Mucopolysaccharidosis type IIIC (MPS IIIC) is a severe neurodegenerative lysosomal storage disease caused by the loss-of-function of the lysosomal transmembrane protein acetyl-CoA: heparan-α-glucosamine <i>N</i>-acetyltransferase. MPS IIIC is characterized by the accumulation of the glycosaminoglycan (GAG) heparan sulfate. There is no treatment for this disease. We generated a new MPS IIIC mouse model and confirmed disease phenotypes such as GAG accumulation, splenomegaly, neurological defects, and presence of disease-specific non-reducing end carbohydrates. To explore a new therapeutic strategy for this condition, we transplanted wild-type (WT) hematopoietic stem and progenitor cells (HSPCs) into lethally irradiated 2-month-old <i>Hgsnat</i>^-/- mice and analyzed the resulting impact 6 months later. Transplanted HSPCs differentiated into macrophages in tissues and microglia-like cells in the brain. This resulted in a partial restoration of <i>Hgsnat</i> expression and enzymatic activity along with a significant reduction of the MPS IIIC-specific non-reducing end carbohydrate in the treated <i>Hgsnat</i>^-/- mice compared to untreated <i>Hgsnat</i>^-/- mice or <i>Hgsnat</i>^-/- mice transplanted with <i>Hgsnat</i>^-/- HPSCs. In addition, WT HSPC transplant resulted in improved neurological defects, reduction in splenomegaly, and urine retention in the <i>Hgsnat</i>^-/- mice. Furthermore, presence of glomerular hyaline bodies with focal fibrosis and sclerosis was observed in the kidney of the disease controls, whereas these abnormalities were improved in the <i>Hgsnat</i>^-/- mice treated with WT HSPCs. These data support that HSPC transplantation presents a promising therapeutic avenue for MPS IIIC and represents the first step toward the clinical translation of an HSPC-mediated therapy strategy for MPS IIIC.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251323966"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Glial Scar: To Penetrate or Not for Motor Pathway Restoration?","authors":"Tetsuji Sekiya, Matthew C Holley","doi":"10.1177/09636897251315271","DOIUrl":"10.1177/09636897251315271","url":null,"abstract":"<p><p>Although notable progress has been made, restoring motor function from the brain to the muscles continues to be a substantial clinical challenge in motor neuron diseases/disorders such as spinal cord injury (SCI). While cell transplantation has been widely explored as a potential therapeutic method for reconstructing functional motor pathways, there remains considerable opportunity for enhancing its therapeutic effectiveness. We reviewed studies on motor pathway regeneration to identify molecular and ultrastructural cues that could enhance the efficacy of cell transplantation. While the glial scar is often cited as an intractable barrier to axon regeneration, this mainly applies to axons trying to penetrate its \"core\" to reach the opposite side. However, the glial scar exhibits a \"duality,\" with an anti-regenerative core and a pro-regenerative \"surface.\" This surface permissiveness is attributed to pro-regenerative molecules, such as laminin in the basement membrane (BM). Transplanting donor cells onto the BM, which forms plastically after injury, may significantly enhance the efficacy of cell transplantation. Specifically, forming detour pathways between transplanted cells and endogenous propriospinal neurons on the pro-regenerative BM may efficiently bypass the intractable scar core and promote motor pathway regeneration. We believe harnessing the tissue's innate repair capacity is crucial, and targeting post-injury plasticity in astrocytes and Schwann cells, especially those associated with the BM that has predominantly been overlooked in the field of SCI research, can advance motor system restoration to a new stage. A shift in cell delivery routes-from the traditional intra-parenchymal (InP) route to the transplantation of donor cells onto the pro-regenerative BM via the extra-parenchymal (ExP) route-may signify a transformative step forward in neuro-regeneration research. Practically, however, the complementary use of both InP and ExP methods may offer the most substantial benefit for restoring motor pathways. We aim for this review to deepen the understanding of cell transplantation and provide a framework for evaluating the efficacy of this therapeutic modality in comparison to others.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251315271"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple stem cell infusion alleviated graft-versus-host disease and improves outcomes in unmanipulated haploidentical hematopoietic stem cell transplantation.","authors":"Fang Hua, Shan Zhang, Xiaomei Zhang, Yan Deng, Ying Han, Sihan Lai, Ying He, Lei Ma, Xupai Zhang, Dan Chen, Yi Su, Jian Xiao, Ling Zhang, Hui Yang, Rong Huang, Haiyan Hu, Mingli Chen, Guangcui He, Hao Yao, Hai Yi","doi":"10.1177/09636897251359786","DOIUrl":"10.1177/09636897251359786","url":null,"abstract":"<p><p>Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) provides cure opportunity for patients requiring prompt allogeneic HSCT but failing to identify well-matched donor, but its outcomes are potentially impaired by increased transplant-related mortality (TRM). We performed haplo-HSCT using granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cells (PBSCs), umbilical cord mesenchymal stem cells (UC-MSCs) and third-party unrelated umbilical cord blood (UCB) stem cells. Modified \"Beijing protocol\" were performed in this study. All of the patients were transplanted by Busulfan or TBI-based regimen. Anti-thymocyte globulin were used to T-cell depletion <i>in vivo</i>. Cyclosporine, mycophenolate mofetil, and short course methotrexate were used to prevent graft-versus-host disease (GVHD). One hundred and sixty-five patients with hematological disorders undergoing haplo-HSCT from Jan 2021 to Nov 2023 were included in this study. The median time of neutrophil engraftment were 12 days (range: 9-25 days), and the median time of platelet engraftment were 13 days (range: 6-50 days). Full haploidentical donor chimerism were obtained within 30 days. No evidence of UCB chimerism was found. Twenty-five patients developed acute GVHD. The incidence of grade II-IV and grade III-IV acute GVHD was 12.73% and 6.67%, respectively. Twenty-eight patients developed chronic GVHD, 10 were limited (6.06%) and 18 were extensive (10.91%). The TRM is total of 26 deaths (15.8%) and the cumulative incidence of relapse (CIR) is total of 17 deaths (11.8%) occurred as of the statistical period. The 2 years overall survival (OS) rate is 72.96%. The median overall survival rate was not reached. Haplo-HSCT performed by PBSCs, UC-MSCs and UCB \"triple-infusion\" achieved excellent outcomes, and need to explored in a larger cohort.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251359786"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating the future of diabetes treatment: Autologous CiPSC-derived islets take center stage.","authors":"Ying Lou","doi":"10.1177/09636897251366828","DOIUrl":"10.1177/09636897251366828","url":null,"abstract":"<p><p>The recent clinical success of chemically induced pluripotent stem cell (CiPSC)-derived islet transplantation for type 1 diabetes represents a landmark achievement in regenerative medicine. This article delves into the groundbreaking work presented by Dr. Hongkui Deng and Dr. Candice S.Y. Liew at International Society for Stem Cell Research (ISSCR) 2025, focusing on their innovative chemical reprogramming technology and its clinical application. The discussion highlights the scientific rationale behind chemical reprogramming, the development of functional islets, the novel transplantation strategy, and the remarkable clinical outcomes observed in their first patient. The implications for future stem cell therapies and the challenges of scalability are also explored.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251366828"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Rheumatoid Arthritis Therapy.","authors":"Guangyang Liu, Herui Wang, Chenliang Zhang, Xin Li, Yi Mi, Yaoyao Chen, Liqiang Xu, Li Miao, Haomiao Long, Yongjun Liu","doi":"10.1177/09636897241301703","DOIUrl":"10.1177/09636897241301703","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells and serves as a primary trigger of inflammation and joint damage in RA. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown potential in alleviating the symptoms of RA. Previous <i>in vitro</i> studies indicate that TNF-α secreted by T cells can activate NF-κB in human MSCs, thereby triggering the immunoregulatory capacity of MSCs in a manner dependent on tumor necrosis factor receptor 1 (TNFR1). Inspired by these findings, we aimed to evaluate whether TNFR1 determine the therapeutic effects of hUC-MSCs on RA. First, we investigated whether TNFR1 is necessary for hUC-MSCs to inhibit TNF-α production of PBMCs, a source of elevated TNF-α in patients. Through coculture experiment, we confirmed that this inhibition was dependent on TNFR1. Subsequently, we administered hUC-MSCs or siTNFR1-MSCs to DBA/1J male mice with collagen-induced arthritis. The results indicated that hUC-MSCs significantly alleviated the pathological features of RA and suppressed the inflammatory cytokines IFN-γ, TNF-α, and IL-6 in peripheral blood, also in a manner dependent on TNFR1 either. Given the dramatic pathologic differences between hUC-MSCs and siTNFR1-MSCs treatments, we questioned whether production of growth factors and chemokines was significantly influenced by TNFR1. Consequently, we stimulated hUC-MSCs or siTNFR1-MSCs through IFN-γ, TNF-α, and IL-6, and profiled growth factors and chemokines in serum, which revealed significant changes of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), as well as chemokines CXCL9, CXCL10, IL-8, and RANTES. In summary, our findings suggest that TNFR1 may determine whether hUC-MSCs will gain abilities of anti-inflammation and tissue regeneration.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241301703"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trans-Vessel Wall Cell Transplantation, Engraftment, and Tumor Access in the VX2 Rabbit Model.","authors":"Victoria Lövljung, Mathias Waldén, Mikael Sandell, Peter Damberg, Staffan Holmin, Fabian Arnberg Sandor","doi":"10.1177/09636897251313678","DOIUrl":"10.1177/09636897251313678","url":null,"abstract":"<p><p>The trans-vessel wall device (TW-device) is a new endovascular tool for precise and safe delivery of various payloads (cells, viral, modified RNA, chemotherapy, growth factors) in oncology and regenerative medicine. The twofold aim of this study was to assess cell engraftment and tumor growth using the TW-device for endovascular transplantation and to evaluate its ability to directly access solid tumors. We used the VX2 model in the rabbit kidney to compare percutaneously implanted fresh VX2 cells with TW-device injections of cryopreserved VX2 cells. We demonstrated the feasibility of endovascular transplantation (<i>n</i> = 7) of tumor cells, achieving a 57.1% engraftment rate despite cryopreservation, comparable with 70% for percutaneous delivery of fresh cells (<i>n</i> = 10). Re-access using the TW-device was 100% successful (<i>n</i> = 11) with super-selective intratumoral contrast administration without complications. In conclusion, endovascular transplantation of VX2 cells using the TW-device resulted in proliferating cell grafts in the rabbit kidney establishing functional proof that cells indeed survive handling, preparation, and device passage. We also show the TW-device is able to access solid tumor parenchyma allowing precise intraparenchymal administration.This proof-of-concept study open up possibilities for repeated direct parenchymal injections via the endovascular route in any hard to reach organ.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251313678"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic effect of body mass index in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation: A retrospective cohort study.","authors":"Jing Yu, Zhuoyue Shi, Hengwei Wu, Yi Luo, Jian Yu, Yamin Tan, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Luxin Yang, Congxiao Zhang, He Huang, Jimin Shi, Yanmin Zhao","doi":"10.1177/09636897251349377","DOIUrl":"10.1177/09636897251349377","url":null,"abstract":"<p><p>Obesity is a well-known risk factor for many diseases, but the impact of baseline body mass index (BMI) on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial. To elucidate the influence of pretransplant BMI on post-allo-HSCT outcomes including graft-versus-host disease (GVHD), overall survival (OS), relapse-free survival (RFS), and nonrelapse mortality (NRM), we conducted a retrospective study using registry data which comprised 1092 adult patients who underwent allo-HSCT between 2015 and 2023. Among the 1092 eligible patients (53.2% male), 56.5% were normal-weight; 24.8% were overweight and 9.1% were obese. Multivariable analyses revealed that compared with normal-weight patients, obese individuals had a higher risk of grade II-IV and III-IV acute GVHD (aGVHD), especially in the gastrointestinal system, with aHRs of 2.08 (95% CI, 1.47-2.94), 2.60 (95% CI, 1.52-4.44), and 3.71 (95% CI, 2.00-6.88), respectively. The probability of OS and RFS was significantly lower in overweight (<i>P</i> = 0.034, <i>P</i> = 0.015, respectively) and obese patients (<i>P</i> = 0.033, <i>P</i> = 0.024, respectively) as compared with normal-weight patients, with aHRs increasing by ~38% (aHR, 1.38; 95% CI, 1.03-1.86), ~40% (aHR, 1.40; 95% CI, 1.07-1.83), ~58% (aHR, 1.58; 95% CI, 1.04-2.40), and ~56% (aHR, 1.56; 95% CI, 1.06-2.29), respectively. Furthermore, the NRM of obese patients was statistically higher than normal-weight patients (<i>P</i> = 0.02, sHR, 2.19; 95% CI, 1.12-4.27). A subgroup analysis revealed that the adverse effects of obesity on OS, RFS, and NRM were primarily observed in the subgroup of patients aged < 40 years and patients with acute lymphoblastic leukemia. The increased risk of grade II-IV aGVHD due to obesity was observed across all subgroups. In conclusion, Obesity prior to allo-HSCT increases the risk of aGVHD and NRM, leading to poorer OS. These findings underscore the importance of closely monitoring high-risk patients and offering opportunities for early intervention.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251349377"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}