Transplantation and Cellular Therapy最新文献

{"title":"Allogeneic Stem Cell Transplantation in Participants With Hematologic Malignancies Following Pembrolizumab Therapy.","authors":"John Kuruvilla, Philippe Armand, Alex F Herrera, Vincent Ribrag, Catherine Thieblemont, Bastian von Tresckow, Guoqing Wang, Patricia Marinello, Samhita Chakraborty, Robert Orlowski, Pier Luigi Zinzani","doi":"10.1016/j.jtct.2025.02.022","DOIUrl":"10.1016/j.jtct.2025.02.022","url":null,"abstract":"<p><p>The safety and efficacy of allogeneic stem cell transplantation (allo-SCT) following antiprogrammed cell death protein 1 (PD-1) therapy in participants with hematologic malignances is of high clinical interest. To present outcomes in participants enrolled in 4 clinical trials who underwent allo-SCT within 2 years of their last dose of pembrolizumab therapy. This analysis included participants from the phase 1b KEYNOTE-013 study (n = 20), the phase 2 KEYNOTE-087 study (n = 31), the phase 2 KEYNOTE-170 study (n = 5), and the phase 3 KEYNOTE-204 study (n = 14). Outcomes of interest included acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS) and overall survival (OS), transplant-related mortality (TRM), and relapse. Of 70 participants included in the analysis, 57 had classical Hodgkin lymphoma (cHL) and the remainder had B-cell non-Hodgkin lymphoma, multiple myeloma, and myelodysplastic syndrome. Overall, 31 participants (44%) were in remission at first allo-SCT. The median duration of treatment with pembrolizumab was 5.3 months (range, 0.7 to 29.6), and the median time from last dose of pembrolizumab to allo-SCT was 4.6 months (range, 1 to 20). The estimated 6-month cumulative incidence of grade II-IV acute GVHD was 41% (95% confidence interval [CI], 30% to 53%); the estimated 6-month cumulative incidence of grade III-IV acute GVHD was 20% (95% CI, 12% to 30%). The estimated 1-year incidence of chronic GVHD was 19% (95% CI, 11% to 29%). After a median follow-up of 40.1 months, both the estimated median PFS and median OS after allo-SCT were not reached; the 40-month PFS rate was 56.8% and the 40-month OS rate was 76.5%. The estimated 40-month cumulative incidence of TRM and relapse was 17% (95% CI, 9% to 27%) and 27% (95% CI, 16% to 38%), respectively. Among participants with cHL (median follow-up, 39.5 months), both the estimated median PFS and median OS after allo-SCT were not reached; the 40-month PFS rate was 59.7% and the 40-month OS rate was 83%. The estimated 40-month cumulative incidence of TRM and relapse in participants with cHL was 12% (95% CI, 5% to 23%) and 23% (95% CI, 12% to 36%), respectively. Overall, the incidences of acute and chronic GVHD in this cohort were within the expected ranges. PFS and OS outcomes were favorable, and the rates of TRM and relapse were low. These results support allo-SCT as a useful and feasible salvage option after anti-PD-1 therapy.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568322","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":"Pretransplant Chromosome Genomic Array Testing Improves Prognostication for Myelofibrosis Patients Undergoing Transplantation","authors":"Xiaoyu Qu ,&nbsp;Emily Stevens ,&nbsp;Matthew P. Fitzgibbon ,&nbsp;Lan Beppu ,&nbsp;Tim M. Monahan ,&nbsp;Cecilia Yeung ,&nbsp;Derek L. Stirewalt ,&nbsp;David Wu ,&nbsp;Jerald P. Radich ,&nbsp;H. Joachim Deeg ,&nbsp;Min Fang","doi":"10.1016/j.jtct.2024.12.018","DOIUrl":"10.1016/j.jtct.2024.12.018","url":null,"abstract":"<div><h3>Background</h3><div>Despite its known superior diagnostic yield for chromosomal anomalies compared with karyotype and fluorescence in situ hybridization (FISH) studies, chromosome genomic array testing (CGAT) is not used as a routine clinical test for myelofibrosis. Although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome.</div></div><div><h3>Objective</h3><div>The current study aimed at testing whether CGAT results obtained before transplantation improves prognosis of post-transplant outcome in patients with myelofibrosis compared with current risk categorization systems, for example, DIPSS plus (Dynamic International Prognostic Scoring System).</div></div><div><h3>Study Design</h3><div>We studied patients with myelofibrosis who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (N = 44). We assessed the prognostic significance of CGAT, DIPSS plus, and the total count of gene mutations for post-transplant clinical outcomes, including relapse-free survival (RFS), overall survival (OS), and graft-versus-host-disease (GVHD).</div></div><div><h3>Results</h3><div>Abnormal CGAT results were seen in 24 patients (55%), including 18 with copy-neutral loss of heterozygosity (cnLOH, 41%). With a median follow-up of 91 (range 2-258) months starting from the CGAT sample date, RFS was 59% and OS was 68%. The outcome analysis showed significant prognostic implication from CGAT (normal vs. abnormal), specifically for patients with intermediate risk by DIPSS-plus scores and those with 0∼2 mutations. CGAT alone significantly stratified the patients’ RFS outcome (<em>P</em> = .03). The addition of CGAT to DIPSS-plus improved the significance from a <em>P</em> value of .08 to .003, whereas the addition of CGAT to mutation count improved the <em>P</em> value from .02 to .01. The best stratification system for RFS was achieved when CGAT, DIPSS-plus, and mutation count were all considered (<em>P =</em> 1e-08). The current study also confirmed individual anomalies that are prognostically significant, including <em>U2AF1</em> mutation (n = 5, <em>P</em> = .03) and 1q gain (n = 3, <em>P</em> = .01), which were associated with worse RFS. <em>ASXL1</em> mutations (n = 14) appeared to associate with a later onset of chronic GVHD (<em>P</em> =.03).</div></div><div><h3>Conclusion</h3><div>Pretransplant CGAT analysis augments the existing risk stratification tools and may be considered as routine clinical testing for myelofibrosis.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 170.e1-170.e8"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898500","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 ,&nbsp;Lucille Langenberg ,&nbsp;Nathan Luebbering ,&nbsp;Azada Ibrahimova ,&nbsp;Kasiani C. Myers ,&nbsp;Anthony Sabulski ,&nbsp;Christopher Dandoy ,&nbsp;Kelly Lake ,&nbsp;Assem Ziady ,&nbsp;Adam Lane ,&nbsp;Aaron Webster ,&nbsp;Sheyar Abdullah ,&nbsp;Sonata Jodele ,&nbsp;Stella M. Davies","doi":"10.1016/j.jtct.2025.01.880","DOIUrl":"10.1016/j.jtct.2025.01.880","url":null,"abstract":"<div><div>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, <em>P &lt; .</em>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, <em>P &lt; .</em>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 (<em>P = .</em>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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 135.e1-135.e10"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","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":"Clinical Outcomes of Early WT1 mRNA Reduction After Remission Induction in Newly Diagnosed Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation","authors":"Takafumi Tsushima,&nbsp;Chiharu Kimeda,&nbsp;Natsumi Yoda,&nbsp;Kosuke Matsuo,&nbsp;Kazusuke Tanaka,&nbsp;Yasuhito Hatanaka,&nbsp;Rena Matsumoto,&nbsp;Sonoko Shimoji,&nbsp;Yoshikazu Utsu,&nbsp;Shin-Ichi Masuda,&nbsp;Nobuyuki Aotsuka","doi":"10.1016/j.jtct.2024.12.007","DOIUrl":"10.1016/j.jtct.2024.12.007","url":null,"abstract":"<div><div><em>Wilms’ Tumor 1 (WT1)</em> mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of <em>WT1</em> mRNA after initial remission induction of patients with AML who have received transplant treatments. Thus, we retrospectively analyzed the clinical features and prognostic impact of <em>WT1</em> mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in <em>WT1</em> mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction. This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had <em>WT1</em> mRNA quantified. Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in <em>WT1</em> mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in <em>WT1</em> mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS. We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in <em>WT1</em> mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of <em>WT1</em> mRNA reduction after initial remission induction.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 168.e1-168.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855577","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":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(25)01015-2","DOIUrl":"10.1016/S2666-6367(25)01015-2","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A1"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610669","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":"Real-World Patient-Reported and Neurocognitive Outcomes in the Year After Axicabtagene Ciloleucel","authors":"Aasha I. Hoogland ,&nbsp;Xiaoyin Li ,&nbsp;Karnav Modi ,&nbsp;Taylor Welniak ,&nbsp;Yvelise Rodriguez ,&nbsp;Nathaly Irizarry-Arroyo ,&nbsp;Laura B. Oswald ,&nbsp;Julia T. Snider ,&nbsp;Sally W. Wade ,&nbsp;Julio Chavez ,&nbsp;Salvatore Corallo ,&nbsp;Margaret Booth-Jones ,&nbsp;Michael D. Jain ,&nbsp;Frederick L. Locke ,&nbsp;Heather S.L. Jim","doi":"10.1016/j.jtct.2024.12.020","DOIUrl":"10.1016/j.jtct.2024.12.020","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy, has significantly improved clinical outcomes in adult patients with relapsed/refractory large B-cell lymphoma. However, few studies have examined patient-reported outcomes (PROs) or neurocognitive performance in patients treated with axi-cel. Moreover, no longitudinal PRO study has reported on patients treated with axi-cel as standard of care in the United States, to our knowledge. This paper reports on real-world changes in PROs (i.e., quality of life [QOL] and perceived cognition) and objective neurocognitive performance before treatment with axi-cel and in the first year after. Patients scheduled to receive axi-cel as standard of care were recruited from a single cancer center between March 2020 and June 2022. QOL was assessed using the EORTC QLQ-C30 and EQ-5D-5L at baseline recruitment (ie, prior to conditioning chemotherapy before axi-cel), and at 7, 14, 30, 60, 90, 180, and 360 days after receiving axi-cel. Perceived cognition was assessed using the Patient-Reported Outcomes Measurement Information System Cognitive Function 4a scale. Objective neurocognitive performance was assessed using a battery of tests at baseline, and 30, 90, and 360 days after receiving axi-cel. Random-effects mixed models evaluated changes in QOL, perceived cognition, and neurocognitive performance using all available data. Clinically meaningful change in QOL was defined as a difference of 10 points on the EORTC QLQ-C30. Clinically meaningful change in perceived cognition or neurocognitive performance was defined as a difference of 5 points. On average, participants (&lt;em&gt;N&lt;/em&gt; = 53) were 63 years of age (SD = 13), and predominantly male (62%), White (92%), and college graduates (60%). Participants reported statistically significant improvements from baseline to day 360 in overall QOL, physical functioning, role functioning, and social functioning (&lt;em&gt;P&lt;/em&gt;s &lt; .05) after axi-cel, despite clinically significant worsening in the first 14 days. For role functioning and social functioning, improvements also met criteria for clinical significance. There were no statistically (&lt;em&gt;P&lt;/em&gt;s &gt; .05) or clinically significant changes in perceived cognition over time. Despite some transient declines, neurocognitive performance generally returned to or exceeded baseline levels by day 360 (&lt;em&gt;P&lt;/em&gt;s &lt; .01). However, visuospatial ability worsened by day 90 and did not recover to baseline levels by day 360 (&lt;em&gt;P&lt;/em&gt; &lt; .0001). These real-world data suggest that axi-cel is associated with significant improvements in overall QOL in the first year after infusion. These data are generally consistent with, or exceed, improvements in QOL reported from clinical trials of axi-cel therapy. Despite transient worsening in the acute period after treatment, neurocognitive performance in most domains also recovered to pretreatment levels by 1 year after infusion. These findings extend previo","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 157.e1-157.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903470","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 ,&nbsp;Qamar Iqbal ,&nbsp;Muhammad Kashif Amin ,&nbsp;Amir Kasaiean ,&nbsp;Iman Menbari Oskouie ,&nbsp;Sarmad Zaman Warraich ,&nbsp;James Yu ,&nbsp;Iqra Anwar ,&nbsp;Michael Jaglal ,&nbsp;Muhammad Umair Mushtaq","doi":"10.1016/j.jtct.2024.12.022","DOIUrl":"10.1016/j.jtct.2024.12.022","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 172.e1-172.e13"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","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":"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}