Transplantation and Cellular Therapy最新文献

{"title":"Impact of Obesity on GVHD in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies.","authors":"Valentina Ardila, Hong Li, Claudio Brunstein, Matt Kalaycio, Ronald Sobecks, Craig S Sauter, Betty K Hamilton","doi":"10.1016/j.jtct.2025.01.881","DOIUrl":"10.1016/j.jtct.2025.01.881","url":null,"abstract":"<p><strong>Background: </strong>The relationship between obesity and graft-versus-host disease (GVHD) has been studied in both preclinical and clinical studies with varying results.</p><p><strong>Objectives: </strong>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.</p><p><strong>Study design: </strong>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).</p><p><strong>Results: </strong>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%, P = .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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress Early After Hematopoietic Stem Cell Transplant.","authors":"Eleanor Cook, Lucille Langenberg, Nathan Luebbering, Azada Ibrahimova, Kasiani C Myers, Anthony Sabulski, Christopher Dandoy, Kelly Lake, Assem Ziady, Adam Lane, Aaron Webster, Sheyar Abdullah, Sonata Jodele, Stella M Davies","doi":"10.1016/j.jtct.2025.01.880","DOIUrl":"10.1016/j.jtct.2025.01.880","url":null,"abstract":"<p><p>HSCT conditioning regimens cause massive lysis of hematopoietic cells with release of toxic intracellular molecules into the circulation. To describe the response to oxidative stress early after hemopoietic stem cell transplantation (HSCT) and assess the association of early oxidative stress with later transplant outcomes. Key components of in the body's physiological response to oxidative stress were studied in a cohort of 122 consecutive pediatric allogeneic HSCT recipients. Glutathione reductase (GSR), glutathione peroxidase (GPX) and glutathione synthetase protein expression was measured using ELISA and reduced and oxidized glutathione (GSH and GSSG) levels were quantified using mass spectrometry. GSR is an inducible enzyme which catalyzes the regeneration of reduced glutathione (GSH). Levels of GSR increased by more than 5-fold between start of conditioning chemotherapy and day 0 (median 87ng/mL to 459ng/mL, P < .0001). GPX catalyzes removal of toxic reactive oxygen species (ROS) by oxidation of GSH. GPX4 levels fell briskly by day 0 (median 20.3 ng/mL prior to HSCT to 7.4ng/mL at day 0, P < .0001), likely indicating consumption of the enzyme as cell lysis and subsequent oxidative stress occurred. Levels of the antioxidant substrate reduced glutathione stayed stable from pre-HSCT through day 14, likely maintained by increased glutathione synthesis by the enzyme glutathione synthetase, whose median levels increased from 38.8ng/mL before conditioning to 54ng/mL at day 21 (P = .02). GSR levels were associated with patient outcomes. Median GSR levels were significantly elevated through days 0-21 in those who died in the first year after HSCT compared to those who survived. Similarly, patients who developed high risk transplant-associated thrombotic microangiopathy (TA-TMA) and grade 2 and above graft versus host disease (GVHD) also had significantly higher GSR levels early after HSCT. Our data suggest that the body is for the most part able to mount a brisk and effective response to the oxidative stress associated with lysis of the hematopoietic cell system before HSCT. Our data also suggest that early events in the first 21 days of HSCT may set the scene for later clinical events in the first year after HSCT. It is plausible that patients who are unable to effectively overcome this early period of significant oxidative stress may have increased endothelial injury and activation of complement. Potential therapeutics to augment and optimize the body's response to oxidative stress may improve outcomes.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012402","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":"Refining Risk Stratification for B-cell Precursor Adult Acute Lymphoblastic Leukemia Treated With a Pediatric-inspired Regimen by Combining IKZF1 Deletion and Minimal Residual Disease.","authors":"Shiyu Deng, Jiawang Ou, Junjie Chen, Zicong Huang, Zihong Cai, Xiuli Xu, Bingqing Tang, Chenhao Ding, Jia Li, Ren Lin, Zhixiang Wang, Ting Zhang, Qifa Liu, Hongsheng Zhou","doi":"10.1016/j.jtct.2025.01.003","DOIUrl":"10.1016/j.jtct.2025.01.003","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Minimal residual disease (MRD) is the most important prognostic factor for B-cell acute lymphoblastic leukemia (B-ALL) however nearly 20-30% of patients relapsed even when they achieved negative MRD, how to identify these patients is less addressed. In this study, we aimed to reassess the prognostic significance of MRD and IKZF1 in adult B-ALL patients receiving pediatric chemotherapy regimens.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methodology: &lt;/strong&gt;A total of 202 newly diagnosed adult patients with B-ALL treated at Nanfang Hospital between January 2016 and September 2020 were enrolled in the population-based protocol of the PDT-ALL-2016 trial (NCT03564470), a GRAALL-backbone, peg-aspargase-intensified, antimetabolite-based pediatric-inspired regimen therapy. The validation dataset COG-P9906, which includes complete gene expression profiles and clinical data for 190 samples, is accessible via the NCBI Gene Expression Omnibus (GEO) at the following link: (https://www.ncbi.nlm.nih.gov/geo/), under the accession code GSE11877.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main findings: &lt;/strong&gt;B-ALL patients were redefined as standard (MRD-negative and IKZF1wild-type), intermediate (MRD-positive or IKZF1 deletion), and high-risk (MRD-positive and IKZF1 deletion) groups by combining IKZF1 deletion status and MRD. In the PDT-ALL-2016 cohort, patients in the high- and intermediate-risk groups who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) exhibited significantly improved 5-year overall survival (OS), event-free survival (EFS), and lower cumulative incidence of relapse (CIR) compared to those who received chemotherapy alone. In the PDT-ALL-2016 cohort, no significant advantage was observed in the 5-year OS, EFS, and CIR of patients in the standard-risk group who received allo-HSCT compared to those who received chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Traditional risk factors, incorporating clinical and cytogenetic features, have been previously evaluated to stratify risks and guide treatment decisions. However, the prognostic strength of this stratified system is limited by the pediatric-inspired protocol background, making it difficult to identify patients with a high risk of relapse. Therefore, in the era of pediatric-inspired protocols, it is imperative to reassess traditional risk factors to identify patients at high risk of recurrence and mortality.In this study, we retrospectively evaluated the combination of MRD and IKZF1 to develop an efficient risk stratification tool for adult patients with B-ALL in the pediatric-inspired chemotherapy era. Moreover, allo-HSCT had distinct efficacy at different risk levels, which means that the decision to perform allo-HSCT may be well guided by this risk classification scheme.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In conclusion, based on our cohort study and validation cohort, we demonstrated that the combination of MRD and IKZF1 deletion allows for better risk stratification of adults with","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972275","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 Association of HLA-E Ligand and NKG2 Receptor Variation With Relapse and Mortality After Haploidentical Related Donor Transplantation.","authors":"Effie W Petersdorf, Caroline McKallor, Mari Malkki, Katherine Hsu, Meilun He, Stephen R Spellman, Theodore Gooley, Philip Stevenson","doi":"10.1016/j.jtct.2025.01.004","DOIUrl":"10.1016/j.jtct.2025.01.004","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","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":"Everolimus with or without Mycophenolate Mofetil for Graft-versus-Host Disease Prophylaxis after Hematopoietic Stem Cell Transplantation in Children with Acute Kidney Injury: A Single-Center Retrospective Analysis.","authors":"Felix Zirngibl, Pimrapat Gebert, Bianca Materne, Michael Launspach, Annette Künkele, Patrick Hundsdoerfer, Sandra Cyrull, Hedwig E Deubzer, Jörn-Sven Kühl, Angelika Eggert, Peter Lang, Lena Oevermann, Arend von Stackelberg, Johannes H Schulte","doi":"10.1016/j.jtct.2025.01.002","DOIUrl":"10.1016/j.jtct.2025.01.002","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants of successful allogeneic HSCT. The immunosuppressive agent cyclosporin A (CsA) is most often used to prevent GVHD in pediatric patients, but it is known to be nephrotoxic. Acute kidney injury (AKI) affects 17% to 47% of pediatric HSCT recipients, compromising clinical outcomes. This retrospective single-institution analysis scrutinized the practice of substituting nephrotoxic CsA with an everolimus/mycophenolate mofetil (MMF) combination as GVHD prophylaxis in 57 patients with AKI (n = 53) or central nervous system side effects due to calcineurin inhibitor (CNI) treatment (n = 4) following first allogeneic HSCT. This retrospective cohort study analyzed the clinical courses of 57 children who were switched from CNI-based GVHD prophylaxis (CsA or tacrolimus in single cases) to the everolimus/MMF combination (n = 48) or everolimus alone (n = 9) after undergoing their first allogeneic HSCT at the Charité University Medicine Berlin. Serving as a control group were 74 patients undergoing their first allogeneic HSCT during the same period who did not receive everolimus at any time post-transplantation. Patients undergoing mismatched family donor transplantation without subsequent CNI treatment for GVHD prophylaxis were excluded. Study endpoints encompassed the retention parameter course subsequent to the GVHD prophylaxis switch, overall survival (OS), and incidences of underlying disease relapse and acute and chronic GVHD in both treatment groups. Renal function improved significantly after switching from CsA to the everolimus/MMF combination. Crucially, the transition to everolimus did not adversely affect OS following HSCT (hazard ratio [HR], 1.6; 95% confidence interval [CI], 0.74 to 3.5; P = .23), especially for patients with nonmalignant diseases (HR, 1.4; 95% CI, 0.34 to 5.9; P = .64). The incidences of grade III-IV acute GVHD (HR, 1.82; 95% CI, 0.45 to 7.4; P = .40) and severe chronic GVHD (HR, 2.76; 95% CI, 0.69 to 11.0; P = .15) were comparable in patients treated with the everolimus/MMF combination and those receiving standard CsA treatment in the control group. OS in patients with malignant underlying diseases was lower in the everolimus group (HR, 2.7; 95% CI, 1.1 to 6.9; P = .03), however, event-free survival was similar in patients with an underlying malignant disease treated with either the everolimus/MMF combination or CsA (HR, 0.87; 95% CI, 0.39 to 1.9; P = .73). Renal function improved significantly in patients who switched their immunosuppression regimen from CsA to everolimus with or without MMF cotreatment after diagnosis of AKI. Patient outcomes in the everolimus group were comparable to those in the control group. This study provides compelling real-world clinical evidence to support replacing CsA with the everolimus/MMF combination in","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955604","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":"Reduced Chimeric Antigen Receptor T Cell Expansion Postinfusion Is Associated with Poor Survival in Patients with Large B Cell Lymphoma after Two or More Therapies.","authors":"Edward Abadir, Rebecca Wayte, Wenlong Li, Sachin Gupta, Shihong Yang, Elizabeth Reaiche, Katrina Debosz, Emily Anderson, James Favaloro, Esther Aklilu, Christina Brown, Christian Bryant, Scott Dunkley, Derek McCulloch, Stephen Larsen, John E J Rasko, Vinay Vanguru, P Joy Ho","doi":"10.1016/j.jtct.2025.01.001","DOIUrl":"10.1016/j.jtct.2025.01.001","url":null,"abstract":"<p><p>CD19-directed chimeric antigen receptor T cell (CAR-T) therapy is now standard of care for relapsed/refractory large B cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR-T therapy. We performed a prospective study using a flow cytometry assay at a single treatment center to assess early CAR T cell expansion in vivo 6 to 9 days after CAR T cell infusion. Early CAR T cell expansion was used in conjunction with additional clinical risk factors to identify those at greater risk of relapse or treatment failure. Forty-four patients treated with commercial CD19-directed CAR-T therapy were included in the study, with a median follow-up of 306 days. CAR T cell expansion of >30 cells/μL was associated with a lower risk of disease progression or death (hazard ratio, 0.34; P = .048), but did not correlate with the risk of death alone. Patients who had poor early CAR T cell expansion (<30 cells/μL) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free survival and overall survival. High LDH level alone was not a statistically significant risk factor for death or disease progression, and thus the interaction between CAR T cell expansion and this clinical risk factor may be important in predicting response. The mean CAR T cell count was higher in patients with grade 2 to 4 cytokine release syndrome (CRS) compared to those with grade 0 to 1 CRS (54.9 cells/μL versus 25.5 cells/μL; P = .01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation in clinical settings. This study suggests that early assessment of CAR T cell expansion can assist in identifying patients with poor overall survival who may benefit from early intervention or more intensive monitoring.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955613","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 Underlying Disease and Total Body Irradiation on the Incidence of Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation.","authors":"Robert Puckrin, Megan Kinzel, Douglas Stewart, Ahsan Chaudhry, Kareem Jamani, Jan Storek","doi":"10.1016/j.jtct.2024.12.024","DOIUrl":"10.1016/j.jtct.2024.12.024","url":null,"abstract":"<p><p>Multiple factors have been described to influence the risk of acute or chronic graft-versus-host disease (aGVHD or cGVHD) after allogeneic hematopoietic cell transplantation (HCT), including underlying chronic myeloid leukemia (CML) and high-dose total body irradiation (TBI). However, the impact of the underlying disease or low-dose TBI on the risk of GVHD in the modern era has not been determined. The objective of this study was to determine risk factors for GVHD in the modern era in the setting of antithymocyte globulin (ATG)-based GVHD prophylaxis. This retrospective study included 1219 patients with hematologic malignancy who underwent first peripheral blood allogeneic HCT using myeloablative fludarabine and busulfan conditioning ± low-dose total body irradiation, along with ATG, cyclosporine, and methotrexate as GVHD prophylaxis. The adjusted cumulative incidence of GVHD was compared between patient subgroups using multivariable competing risks regression. When disregarding the underlying disease, risk factors for grade 2-4 aGVHD were donor type other than matched sibling donor (non-MSD) and lack of low-dose TBI (non-TBI). Risk factors for grade 3-4 aGVHD were non-MSD, non-TBI, and CMV donor negative/recipient positive serostatus (D-R+). Risk factors for moderate-severe cGVHD were ≤9/10 HLA match, non-male/male donor/recipient sex, and non-TBI. In models including the underlying disease, additional significant risk factors were chronic lymphocytic leukemia (CLL) for grade 2 to 4 aGVHD (sub-hazard ratio over acute myeloid leukemia [SHR] 3.16, 95% CI 1.97-5.08, P < .001); CLL and acute lymphoblastic leukemia (ALL) for grade 3-4 aGVHD (SHR for CLL 3.54, 95% CI 1.54-8.17, P = .003 and SHR for ALL 2.26, 95% CI 1.26-4.04, P = .006); and myelofibrosis (MF) for moderate-severe cGVHD (SHR 2.14, 95 CI 1.34-3.41, P = .001). In the modern era when using ATG for GVHD prophylaxis, newly identified risk factors include CLL and non-TBI for grade 2-4 aGVHD; CLL, ALL, and non-TBI for grade 3-4 aGVHD; and MF and non-TBI for moderate-severe cGVHD. These findings, if confirmed in a separate cohort, should be taken into consideration when tailoring the prophylaxis and monitoring of GVHD.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966616","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":"Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Aged 70 Years and Older: A Systematic Review and Meta-Analysis.","authors":"Moazzam Shahzad, Qamar Iqbal, Muhammad Kashif Amin, Amir Kasaiean, Iman Menbari Oskouie, Sarmad Zaman Warraich, James Yu, Iqra Anwar, Michael Jaglal, Muhammad Umair Mushtaq","doi":"10.1016/j.jtct.2024.12.022","DOIUrl":"10.1016/j.jtct.2024.12.022","url":null,"abstract":"<p><p>Allogeneic hematopoietic cell transplantation (allo-HCT) is a potential cure for many hematological malignancies. Historically, older adults were not considered eligible for allo-HCT due to increased toxicity and mortality concerns. This systematic review and meta-analysis aim to explore the outcomes of allo-HCT in patients aged 70 years or older. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search was performed on PubMed, Cochrane Register of Controlled Trials, and Clinicaltrials.gov using MeSH terms and keywords for \"Hematopoietic Stem Cell Transplantation\" AND \"Outcome Assessment\" from the date of inception to June 30, 2024. Our search produced 102 articles. After excluding irrelevant and review articles during primary and secondary screening, eight original studies reporting outcomes of allo-HCT in patients aged 70 years or older were included. The survival data were retrieved from Kaplan-Meier (KM) curves using an online plot digitizer tool to calculate the overall survival (OS) and disease-free survival (DFS). The pooled KM curves were plotted and analyzed using the \"MetaSurvival\" package of R software version 4.2.1. Proportions and 95% confidence intervals (CIs) were extracted as well. A total of 2519 patients aged 70 years or older with allo-HCT were included in the analysis. The included patients' age ranged from 70 to 84 years, and 68% were male. Median follow-up was 23.2 (0.4 to 122.5) months. The combined median OS was 14.84 months (95% CI: 11.61 to 19.50), with OS rates at 6, 12, 24, and 36 months of 71.8%, 54.5%, 41.9%, and 34.9%, respectively. The estimated pooled mean OS was 28.62 months (95% CI: 23.41 to 31.44). The pooled median DFS was 10.54 months (95% CI: 7.93 to 14.17), with DFS rates at 6, 12, 24, and 36 months of 61.5%, 47.5%, 37%, and 30.6%, respectively. The estimated pooled mean DFS was 24.45 months (95% CI: 18.30 to 23.74). The relapse rate ranged from 28% to 55.6%, while non-relapsed mortality ranged from 5.6% to 42%. The acute graft versus host disease (GvHD) incidence varied from 9.3% to 32%, while chronic GvHD rates ranged from 10% to 43%. Allo-HCT provides promising outcomes for patients aged 70 or older with transplant-eligible diseases. Disease progression, followed by infections, is the leading cause of mortality, underscoring the need for improved post-transplant care, including optimized GvHD regimens and strategies to reduce infection risk.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928472","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":"Donor Type Does Not Impact Late Graft Failure Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis.","authors":"Cindy Lynn Hickey, Mei-Jie Zhang, Mariam Allbee-Johnson, Rizwan Romee, Navneet S Majhail, Monzr M Al Malki, Joseph H Antin, Cara L Benjamin, Christopher Bredeson, Saurabh Chhabra, Michael R Grunwald, Yoshihiro Inamoto, Christopher G Kanakry, Filippo Milano, Robert J Soiffer, Scott R Solomon, Stephen R Spellman, Claudio G Brunstein, Corey Cutler","doi":"10.1016/j.jtct.2024.12.021","DOIUrl":"10.1016/j.jtct.2024.12.021","url":null,"abstract":"<p><strong>Background: </strong>Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12% to 20% in haplo-HCT recipients using PTCy. The objective of this study was to determine whether donor type influenced the risk of late graft failure following reduced-intensity conditioning (RIC) HCT using PTCy-based GVHD prophylaxis.</p><p><strong>Study design: </strong>A retrospective cohort analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database among adult patients who underwent first RIC haplo or 8/8 matched unrelated donor (MUD) HCT between 2011 and 2018 for acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) with PTCy GVHD prophylaxis. The primary outcome was incidence of late graft failure, defined as secondary graft loss in the absence of relapse or poor graft function requiring a cellular therapy intervention.</p><p><strong>Results: </strong>A total of 1336 patients met the eligibility criteria (1151 haplo, 185 MUD). Patients in the MUD group were older (65 vs. 61 years), less ethnically diverse (95% vs. 72% White), received fewer bone marrow grafts (45% vs. 16%), and had younger donors (median age, 28 vs. 37 years old). Conditioning regimens were predominately fludarabine, cyclophosphamide, and total body irradiation (TBI; 87% haplo and 38% MUD). At 2 years, the adjusted probabilities of late graft failure for the haplo group was 6.5% (95% confidence interval [CI], 5.2-8.0) versus 5.9% (95% CI, 2.7%-10.9%) for the MUD group (P = .79). Multivariate analysis for risk factors associated with late graft failure found associations with a diagnosis of MDS (HR, 1.98; 95% CI, 1.22-3.20; P = .005), and earlier year of HCT (2015-2018 vs. 2011-2014; HR, 0.39; 95% CI, 0.24-0.64; P = .0002). A post-hoc sensitivity analysis was performed to evaluate the effect of donor age and use of peripheral blood stem cell (PBSC) grafts. Graft failure did not differ between haplo and MUD HCT (HR, 1.19; P = .67) when adjusted for donor age nor when restricted to PBSC grafts only (HR, 0.85; P = .70).</p><p><strong>Conclusion: </strong>In this registry-based analysis of patients undergoing RIC HCT for AML, ALL, or MDS using GVHD prophylaxis with PTCy, there was no significant difference in late graft failure rates between haplo and MUD donors. Overall rates of late graft failure were high.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928471","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":"Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT","authors":"Machiko Fujioka ,&nbsp;Hidehiro Itonaga ,&nbsp;Hideyuki Nakazawa ,&nbsp;Tetsuya Nishida ,&nbsp;Keisuke Kataoka ,&nbsp;Takashi Ikeda ,&nbsp;Shinichi Kako ,&nbsp;Ken-ichi Matsuoka ,&nbsp;Koji Adachi ,&nbsp;Shin-ichiro Fujiwara ,&nbsp;Nobuyuki Aotsuka ,&nbsp;Toshiro Kawakita ,&nbsp;Emiko Sakaida ,&nbsp;Yoshinobu Kanda ,&nbsp;Tatsuo Ichinohe ,&nbsp;Yoshiko Atsuta ,&nbsp;Yasushi Miyazaki ,&nbsp;Ken Ishiyama","doi":"10.1016/j.jtct.2024.09.026","DOIUrl":"10.1016/j.jtct.2024.09.026","url":null,"abstract":"<div><div>The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with <em>de novo</em> MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; <em>P</em> = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; <em>P</em> = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, <em>P</em> = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, <em>P</em> = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 18.e1-18.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393597","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}