Transplantation and Cellular Therapy最新文献

{"title":"Utility of Thrombopoietin Receptor Agonists for Prolonged Thrombocytopenia After Chimeric Antigen Receptor T-cell Therapy.","authors":"Donald Waddell, Jennifer Collins, Sarvnaz Sadrameli","doi":"10.1016/j.jtct.2025.01.887","DOIUrl":"10.1016/j.jtct.2025.01.887","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment landscape for various hematological malignancies. However, it is associated with a range of hematologic complications, including severe and often prolonged thrombocytopenia. Currently, there are no known effective preventative or management measures against CAR-T-induced thrombocytopenia. At the University of Chicago Medical Center, thrombopoietin receptor agonists (TPO-RAs) eltrombopag and romiplostim have been utilized intermittently, per attending preference, in patients post CAR-T treatment presenting with prolonged thrombocytopenia (platelets <50 × 10<sup>3</sup> cells/μL for at least 14 days). However, whether these treatments yield positive outcomes in this context remains uncertain. This study aims to evaluate the efficacy and safety of TPO-RAs in patients with CAR-T-induced thrombocytopenia. The primary objective is to compare the incidence of platelet recovery (defined as two consecutive platelet counts of ≥50 × 10<sup>3</sup> cells/μL) in patients who received TPO-RAs versus those who did not for CAR-T-associated prolonged thrombocytopenia between January 1, 2018, and June 30, 2023. The secondary objectives include time to platelet recovery, incidence of clinically relevant bleed, hospital length of stay, incidence of adverse effects associated with TPO-RA administration, overall survival, and financial toxicity. This is a single-center, retrospective study conducted at the University of Chicago Medical Center. Eighty-five patients with prolonged, CAR-T-induced thrombocytopenia were enrolled in the study; 12 of these patients were managed with TPO-RA therapy while the remaining 73 received supportive care. Statistical analysis was performed using STATA, incorporating the Chi-squared test for nominal data and the Wilcoxon Rank-sum test for continuous data. A P value of <.05 was used to determine statistical significance. The incidence of platelet recovery was similar between the two groups; in the supportive care group, 53 patients (73%) experienced resolution of thrombocytopenia, compared to 9 patients (75%) in the TPO-RA treated group (P = 1.0). The median time to thrombocytopenia resolution was 56 days in the TPO-RA-treated group and 41 days in those not managed with TPO-RAs (P = .14). The median time to TPO-RA initiation postinfusion was 45 days. There were no statistically significant differences in incidence of clinically relevant bleed or readmission within 1 year of CAR-T infusion between the two groups, but 25% of patients receiving TPO-RA therapy experienced associated arthralgia requiring treatment modification. Additionally, the median cost of a course of eltrombopag was estimated at $86,921.52 per patient at the reported average wholesale price. While TPO-RAs represent a theoretical therapeutic option for CAR-T patients based on their role in chemotherapy-induced thrombocytopenia, our study showed that their use did not provide significa","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068142","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":"Prospective Validation of CAR-HEMATOTOX and a Simplified Version Predict Survival in Patients with Large B-Cell Lymphoma Treated with Anti-CD19 CAR T-Cells: Data from CART-SIE Study.","authors":"Federico Stella, Martina Pennisi, Annalisa Chiappella, Beatrice Casadei, Stefania Bramanti, Silva Ljevar, Patrizia Chiusolo, Alice Di Rocco, Maria Chiara Tisi, Piera Angelillo, Ilaria Cutini, Massimo Martino, Angelica Barone, Francesca Bonifazi, Armando Santoro, Federica Sorà, Mattia Novo, Anna Maria Barbui, Domenico Russo, Maurizio Musso, Giovanni Grillo, Mauro Krampera, Jacopo Olivieri, Lucia Brunello, Federica Cavallo, Massimo Massaia, Luca Arcaini, Lucia Farina, Pierluigi Zinzani, Rosalba Miceli, Paolo Corradini","doi":"10.1016/j.jtct.2025.01.888","DOIUrl":"10.1016/j.jtct.2025.01.888","url":null,"abstract":"<p><strong>Background: </strong>Anti-CD19 CAR T-cells have revolutionized outcomes in relapsed/refractory large B-cell lymphomas. Long-term follow-up underscored the role of hematological toxicity in nonrelapse mortality, largely driven by infections, leading to the development of the CAR-HEMATOTOX (HT) score for predicting neutropenia. The European scientific community (EHA/EBMT) later reached a consensus, defining a new entity: immune effector cell-associated hematotoxicity (ICAHT).</p><p><strong>Aims: </strong>To validate the ability of the HT score to predict ICAHT and survival.</p><p><strong>Methods: </strong>The CART-SIE is an ongoing multicenter prospective observational study collecting data on patients affected by B-cell lymphoma treated with commercial anti-CD19 CAR T-cells (ClinicalTrials.gov ID: NCT06339255).</p><p><strong>Results: </strong>Since 2019 to 2024, 1002 consecutive patients were enrolled. Out of 746 patients infused, the HT score at infusion was evaluable in 389. Median age was 59 years (48-66). Patients with high HT score had greater disease burden and a greater need for bridge therapy. Patients with a HT^HIGH score had a 4-fold higher risk of experiencing late ICAHT of grade≥3 (OR = 3.99, 95% CI = 1.16-13.77, P = .03). Patients with a HT^HIGH score also showed lower overall response rates (ORR) and complete response rates (CRR) at 90 days (CRR at 90 days: 59% HT^LOW versus 38% HT^HIGH, OR = 0.42, 95% CI = 0.27-0.66, P = .0002; ORR at 90 days: 67% HT^LOW versus 49% HT^HIGH, OR = 0.47, 95% CI = 0.29-0.74, P = .001). Adjusted logistic models confirmed that the effect of HT score was independent from baseline characteristics. With a median follow-up of 18 months, patients with a HT^HIGH score have lower OS and PFS (1-year OS: 78% HT^LOW versus 62% HT^HIGH, P = .0002; 1-year PFS: 49% versus 39%, P = .003). Adjusted Cox models confirmed that HT was an independent prognostic factor for OS. A high HT-score was found to be associated with higher risk of secondary primary malignancy (HR=2.8, 95% CI = 1.03-7.8, P = .04). A simplified version of HT (simpleHT), based solely on the platelet count and C-reactive protein at infusion, was calculated for 560 patients and proved significant in predicting both OS and PFS (1-year was 72% simpleHT^LOW versus 37% simpleHT^HIGH, P < .0001, 1-year PFS was 48% simpleHT^LOW versus 22% simpleHT^HIGH, P < .0001).</p><p><strong>Conclusion: </strong>In our prospective real-world study, we validated the ability of the HT score to predict ICAHT and survival. SimpleHT identified a population at very high risk with an impaired progression free and overall survival.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053206","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":"Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.","authors":"Anna Barata, P Connor Johnson, Tejaswini M Dhawale, Richard A Newcomb, Hermion L Amonoo, Mitchell W Lavoie, Dagny Vaughn, Kyle Karpinski, Bridget Coffey, Giuliana V Zarrella, Melissa M Gardner, Jorg Dietrich, Areej El-Jawahri, Michael W Parsons","doi":"10.1016/j.jtct.2025.01.886","DOIUrl":"10.1016/j.jtct.2025.01.886","url":null,"abstract":"<p><strong>Background: </strong>CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.</p><p><strong>Methods: </strong>We assessed perceived cognition (Functional Assessment of Cancer Therapy-Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up. We examined changes in cognitive outcomes using paired T-tests. We used univariate and multivariate linear regression models to explore whether patient-, disease-, or CAR-T specific factors were associated with change in cognition over time.</p><p><strong>Results: </strong>We included 106 participants (mean age = 62.7 years, 60.4% male, 56.6% diagnosed with non-Hodgkin´s lymphoma), of whom 70 reported perceived cognition data and 26 underwent neurocognitive performance assessments at both timepoints. There were no changes in perceived cognition (P = .560), overall neurocognitive performance (P = .924), or neurocognitive domains (P´s > .05) from baseline to 6 months post CAR-T. At 6 months, 32.9% reported improved, 47.1% stable, and 20.0% declined perceived cognition relative to baseline. In unadjusted analyses, progressive disease (β = -8.86, P = .012), baseline elevated C-reactive protein (β = -5.60, P = .076) and baseline neurologic comorbidity (β = -11.4, P = .052) were numerically associated with worse perceived cognition over time. In multivariate analyses, only progressive disease was statistically significantly associated with worse perceived cognition (β = -7.32, P = .032) over time.</p><p><strong>Conclusions: </strong>We found stable cognition among CAR-T recipients and identified an association of therapy response with change in perceived cognition over time.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052636","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":"Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part II. Organ Dysfunction and Immune Reconstitution Considerations for children with chronic GVHD after Hematopoietic Cell Transplantation.","authors":"Saldaña Bj Dávila, K Schultz, A Ramgopal, J R Boiko, K Beebe, P Carpenter, S Chan, S Paczesny, P Aguayo-Hiraldo, G Cuvelier, S J Rotz, C N Duncan, K M Williams","doi":"10.1016/j.jtct.2025.01.885","DOIUrl":"https://doi.org/10.1016/j.jtct.2025.01.885","url":null,"abstract":"<p><p>While highly morbid forms of chronic graft versus host disease (cGVHD) and severe late effects of allogeneic hematopoietic cell transplant (HCT) can impact children and adults alike, unique considerations arise in pediatric cases regarding diagnosis, monitoring, treatment, and likelihood of resolution. As children can present with atypical features of cGVHD, and with more significant disease due to inability to communicate symptoms, they may be at increased risk for highly morbid forms of cGVHD and incur greater subsequent late effects, which may be more pronounced in those with underlying chromosomal breakage syndromes, with higher prevalence in pediatric HCT recipients. The long-term effects of cGVHD and its therapies include impaired immune reconstitution, leading to increased risks of infection and secondary malignant neoplasms. However, children also have the greatest potential for full immune reconstitution, due to thymus recovery that could impact the timing of vaccination with respect to tolerance and restoration of optimal immunity. Developing strategies to mitigate the late effects incurred with, and as a result of cGVHD, is of critical importance. The working group recommends surveillance strategies for late effects in patients with cGVHD, increased utilization of emerging diagnostic tools, integration of monitoring for cGVHD treatment response, development of new treatments, and provides aims for future research endeavors.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042252","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":"Prolonged Neurologic Symptoms Following Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients With Large B-cell Lymphoma Treated With Chimeric Antigen Receptor-Modified T Cell Therapy.","authors":"Luke Maillie, Sunita D Nasta, Jakub Svoboda, Stefan K Barta, Elise A Chong, Alfred L Garfall, Saar I Gill, David L Porter, Stephen J Schuster, Christopher Catania, Noelle V Frey, Daniel J Landsburg","doi":"10.1016/j.jtct.2025.01.884","DOIUrl":"10.1016/j.jtct.2025.01.884","url":null,"abstract":"<p><p>While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-defined adverse effect associated with chimeric antigen receptor-modified T cell (CAR-T) therapy, some patients develop prolonged neurologic symptoms. Few studies have examined characteristics and outcomes of patients who develop such symptoms. The objective of this study was to provide an analysis of patients who developed ICANS in a single-center cohort of patients with large B-cell lymphoma (LBCL) who received commercial CAR-T and compare characteristics and outcomes between patients with vs. without subsequent prolonged neurologic symptoms. We examined a retrospective cohort of patients with LBCL treated with CAR-T at our institution who developed ICANS. Prolonged neurologic symptoms were defined as those lasting longer than four weeks. Thirty three of 278 (12%) LBCL patients treated with commercial CAR-T experienced ICANS. Nine patients (27%) experienced prolonged neurologic symptoms following ICANS, eight with ICANS grade ≥3 (high-grade) and one with ICANS grade <3 (low-grade). There were a range of symptoms experienced by these patients including difficulties with short-term memory, difficulties with long-term memory, aphasia, and tremors. The incidence of prolonged neurologic symptoms was greater in patients experiencing high-grade as compared to low-grade ICANS (42.1% vs. 7.1%, P = .049). However, no other pre-treatment characteristics or post-treatment outcomes were associated with development of prolonged neurologic symptoms following ICANS. In summary, nearly half of all patients with LBCL treated with CAR-T at our institution who developed high-grade ICANS experienced prolonged neurologic symptoms; however, pretreatment characteristics and post-treatment outcomes were not predictive of this clinical condition. Further work is needed to identify patients treated with CAR-T at risk for experiencing prolonged neurologic symptoms and developing strategies for evaluation and treatment of this toxicity.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029712","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":"Risk-Adapted Letermovir Prophylaxis Based on a Scoring System Predicting a Higher Burden of Cytomegalovirus Exposure After Allogeneic Hematopoietic Cell Transplantation.","authors":"Shunto Kawamura, Shin-Ichiro Fujiwara, Shun-Ichi Kimura, Junko Takeshita, Hideki Nakasone, Kazuki Yoshimura, Yuya Nakata, Takuto Ishikawa, Akari Matsuoka, Tomohiro Meno, Yuhei Nakamura, Masakatsu Kawamura, Nozomu Yoshino, Yukiko Misaki, Ayumi Gomyo, Machiko Kusuda, Rui Murahashi, Kento Umino, Daisuke Minakata, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Ken Ohmine, Shinichi Kako, Yoshinobu Kanda","doi":"10.1016/j.jtct.2025.01.883","DOIUrl":"10.1016/j.jtct.2025.01.883","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-17","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":"Low Survival Due to Higher Risk of Relapse and Nonrelapse Mortality After Allogeneic HSCT in ATL Compared with AML and ALL.","authors":"Shohei Tomori, Satoko Morishima, Koji Kato, Hideki Nakasone, Nobuaki Nakano, Tetsuya Eto, Toshiro Kawakita, Youko Suehiro, Yasuhiko Miyazaki, Naoyuki Uchida, Yasushi Sawayama, Yasuo Mori, Hirohisa Nakamae, Koji Nagafuji, Yasufumi Uehara, Noriko Doki, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Makoto Yoshimitsu","doi":"10.1016/j.jtct.2025.01.882","DOIUrl":"10.1016/j.jtct.2025.01.882","url":null,"abstract":"<p><strong>Background: </strong>Patients with adult T-cell leukemia/lymphoma (ATL) are considered to have worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) than patients with other hematological malignancies, owing to high risk of relapse and immunocompromised status. However, no studies have compared transplant outcomes between patients with ATL and those with other hematological malignancies using a large-scale database.</p><p><strong>Objectives: </strong>To compare transplant outcomes between patients with ATL and those with other leukemias and to identify factors contributing to worse transplant outcomes in ATL patients.</p><p><strong>Study design: </strong>Using Japanese registry data, we retrospectively compared transplant outcomes between patients with ATL and those with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As ATL often develops in patients in their 60s or older, patients with ATL, AML, or ALL aged ≥50 years were included in order to compare patients in the same age group. A total of 7764 patients (ATL, n = 1151; AML, n = 5393; ALL, n = 1220) who underwent their first allo-HSCT between January 1, 2006 and December 31, 2017 were included in this study.</p><p><strong>Results: </strong>Compared with AML, ATL showed significantly worse overall survival (OS) (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.14 to 1.34; P < .001) and higher risk of relapse (HR, 1.33; 95% CI, 1.2 to 1.47; P < .001), while there were no significant differences between AML and ALL. Among patients in complete remission (CR) at transplantation, ATL showed worse OS (HR, 1.30; 95% CI, 1.08 to 1.56; P = .006), higher risk of relapse (HR, 1.78; 95% CI, 1.48 to 2.14; P < .001), and higher risk of nonrelapse mortality (NRM) (HR, 1.38; 95% CI, 1.14 to 1.33; P = .001) in comparison with AML, whereas there were no significant differences between AML and ALL.</p><p><strong>Conclusion: </strong>We found that ATL patients have poor transplant outcomes compared with AML or ALL patients. In ATL patients, survival is poor, relapse is more frequent, and NRM is significantly higher, especially in cases of CR. These findings suggest that prevention of relapse and transplant-related complications is important for successful allo-HSCT in ATL.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012398","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, 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}