Bone Marrow Transplantation最新文献

{"title":"Extramedullary disease but not paraskeletal disease portends inferior outcomes after CAR T cell therapy in multiple myeloma.","authors":"Darren Pan, Tarek H Mouhieddine, Tianxiang Sheng, Weijia Fu, Erin Moshier, Joshua Richter, Samir Parekh, Sundar Jagannath, Adriana C Rossi, Larysa J Sanchez, Santiago Thibaud, Cesar Rodriguez, Hearn J Cho, Shambavi Richard","doi":"10.1038/s41409-025-02593-3","DOIUrl":"https://doi.org/10.1038/s41409-025-02593-3","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy is effective for multiple myeloma (MM), yet patients with plasmacytomas, either paraskeletal disease (PSD) or extramedullary disease (EMD), have poorer outcomes. To better distinguish the effects of EMD and PSD on outcomes, we conducted a single-center, retrospective study of 134 relapsed/refractory MM patients treated with CAR T cells. With a median follow-up of 30.2 months, patients with EMD (n = 34) had significantly worse progression-free survival (PFS) and overall survival (OS) than those with bone marrow-only disease (n = 75): PFS was 24.2 months vs. 9.0 months (HR 2.15, 95% CI 1.31-3.54), and OS was not reached vs. 24.0 months (HR 3.79, 95% CI 1.81-7.94). In contrast, patients with PSD did not experience significantly shorter PFS or OS. Among patients with EMD, those with high extramedullary tumor burden had a lower overall response rate (ORR). For extramedullary tumor burden <25 cm², 25-50 cm², and >50 cm², ORR was 81.0% (66.7% complete response, CR), 83.3% (50% CR), and 57.1% (0% CR), respectively. Importantly, EMD-positive relapses post-CAR T cell therapy comprised half of all relapses observed. In summary, our findings indicate that EMD, but not PSD, is strongly associated with poor outcomes with CAR T cell therapy.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms underlying seizures and hypothermia during busulphan administration.","authors":"Ibrahim El-Serafi, Sofia Berglund, Fadwa BenKessou, Alina Codita, Maryam Saghafian, David Lindskog, Matthijs C Dorst, Gilad Silberberg, Manuchehr Abedi-Valugerdi, Wenyi Zheng, Rui He, Manon Renault, Weiying Zhou, Chao Yu, Massoud Vosough, Sandra Oerther, Ying Zhao, Jonas Mattsson, Moustapha Hassan","doi":"10.1038/s41409-025-02608-z","DOIUrl":"https://doi.org/10.1038/s41409-025-02608-z","url":null,"abstract":"<p><p>Busulphan (Bu) is used as a part of the conditioning regimen prior to HSCT. Neurotoxicity is one of Bu major adverse-effects. We investigated the kinetics of busulphan and its metabolites (tetrahydothiophene, tetrahydrothiophene-1-oxide, sulfolane, 3-OH-sulfolane) in patients and mice as well as the mechanisms underlying CNS-toxicity in mice. Busulphan metabolites were detectable in plasma and urine up to 72-h after the last Bu-dose. Sulfolane levels were high and reached maximum concentration at the time-point reported for the convulsions' occurrence. Mice were treated with either busulphan or one of its metabolites, separately. Sulfolane treated-mice showed the highest brain exposure (AUC_brain/AUC_plasma). Seizures and hypothermia were observed after sulfolane administration, accompanied with a significant decrease in calbindin-28k concentrations in the brain. Behavior changes but no signs of convulsions were seen in mice treated with lower sulfolane doses. Moreover, a reduction of spontaneous events during whole-cell patch clamp recordings from pyramidal neurons was observed following bath application of sulfolane. In conclusion, these are the first results showing that sulfolane is the major cause of seizures and hypothermia. Sulfolane concentration in plasma mirrors its concentration in the brain. The role of calbindin-D28K in CNS-toxicity and susceptibility to future neurodegenerative diseases should be investigated.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abatacept for acute graft versus host disease prophylaxis in children with sickle cell disease patients undergoing HLA identical sibling hematopoietic stem cell transplantation.","authors":"Azada Ibrahimova, Ruby Khoury, Sonata Jodele, Michael Grimley, Stella M Davies, Pooja Khandelwal","doi":"10.1038/s41409-025-02601-6","DOIUrl":"https://doi.org/10.1038/s41409-025-02601-6","url":null,"abstract":"<p><p>Abatacept reduces the risk of acute graft versus host disease (GVHD) in matched unrelated donor hematopoietic stem cell transplant (HSCT) for Sickle Cell Disease (SCD). We conducted a retrospective review of patients who underwent matched sibling donor (MSD) HSCT for SCD with and without adding abatacept to standard acute GVHD prophylaxis. Twenty-one patients, median age 7 years (range 2.0-14.8) received MSD HSCT with addition of 4 doses of abatacept to standard calcineurin inhibitor based acute GVHD prophylaxis while six patients, median age 9.8 years (range 1.9-14.4) underwent MSD HSCT with standard prophylaxis. One patient (4.5%) in the abatacept group developed grade II acute skin GVHD, while 3 patients (50%) in standard group developed grade II-III acute skin and gut GVHD (p = 0.022). Grade III-IV GVHD was 0% in abatacept group compared to 33% in standard group (p = 0.043). Disease-free survival was 83% in standard group at a median follow up of 11 years (IQR:9.5-13.25 years), and 100% in the abatacept group at a median follow up of 5 years (IQR:3-8 years). Our data show that addition of abatacept to calcineurin inhibitor based acute GVHD prophylaxis reduces the risk of severe acute GVHD in patients with SCD undergoing MSD HSCT without impacting disease-free survival.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Endothelial Activation and Stress Index (EASIX)-based predictive model for cytokine release syndrome and neurotoxicity after B-cell maturation antigen directed chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma.","authors":"Utkarsh Goel, Danai Dima, James A Davis, Aliya Rashid, William Wesson, Louis Williams, Sandra Mazzoni, Evguenia Bhurtel, Fauzia Ullah, Joslyn Rudoni, Mikhaila Rice, Yun Kyoung Ryu Tiger, Craig S Sauter, Faiz Anwer, Shahzad Raza, Leyla Shune, Jack Khouri","doi":"10.1038/s41409-025-02612-3","DOIUrl":"https://doi.org/10.1038/s41409-025-02612-3","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of human leukocyte antigen matched sibling transplant from consanguineous versus non-consanguineous parents, a single center experience.","authors":"Riad El Fakih, Mohamed I Sharif, Shaykhah Alotaibi, Abdulrahman Almujalli, Sara Samarkandi, Salman Almhareb, Yasamiyan Saud Alsgaih, Feras Alfraih, Saud Alhayli, Syed Osman Ahmed, Marwan Shaheen, Naeem Chaudhri, Fahad Alsharif, Amr Hanbali, Ayman Saad, Abdullah Alamer, Alfadel Alshaibani, Mansour Alfayez, Abdulwahab A Albabtain, Hanan Alkhaldi, Ahmad S Alotaibi, Tusneem Elhassan, Fahad Almohareb, Ali Alahmari, Ghulam Mufti, Walid Rasheed, Hazzaa Alzahrani, Mahmoud Aljurf","doi":"10.1038/s41409-025-02609-y","DOIUrl":"https://doi.org/10.1038/s41409-025-02609-y","url":null,"abstract":"<p><p>Matching HLA between donor and recipient pairs significantly improves engraftment and decreases GvHD. However, even in HLA matched siblings, the risk of graft failure and GvHD still exist and is partially attributed to the bidirectional alloreactivity generated from minor histocompatibility antigens (miHA) mismatching between donors and recipients. Consanguineous marriage increases the chance of miHA matching. This fact may be an advantage or disadvantage in consanguineous MSD transplants. We retrospectively reviewed our institutional transplant registry and selected AML and ALL patients who received a MSD allo-HCT between January 2006 and December 2020. The objective was to compare the outcomes of transplant among consanguineous vs non-consanguineous pairs. Analysis was conducted using RStudio. Version 1.4.1106 © 2009-2021 RStudio, PBC. 271 patients met the eligibility criteria were included in this study. Sixty-three were consanguineous and 208 were not. The median follow-up time was 72.6 months. The five years OS and DFS were not statistically different between consanguineous and non-consanguineous group. A trend toward a higher relapse rate in the consanguineous group was observed. The five years NRM for the whole group was 10.5% with no statistically significant difference between groups. The grade II-IV aGvHD incidence was 25.8% for the whole group with no statistically significant difference between groups. The all grade cGvHD incidence was 52.8% with no statistically significant difference between groups. Populations with high levels of consanguinity, complex consanguinity loops often arise from cousin marriages across multiple generations. This means that even individuals who consider themselves non-consanguineous may still share genetic traits associated with consanguinity. Therefore, high level of homozygosity probably exist in the non-consanguineous cohort and explain these results.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Objective quantification of pre-CAR-T EEG abnormalities for ICANS prognosis: insights from GTE scoring.","authors":"Hidetaka Nakagaki, Takuji Yamauchi, Takahiko Mukaino, Ayumi Sakata, Eriko Watanabe, Mitsuru Watanabe, Daisuke Ishihara, Hiroshi Imanaga, Kensuke Sasaki, Teppei Sakoda, Fumiaki Jinnouchi, Kohta Miyawaki, Takahiro Shima, Yoshikane Kikushige, Yasuo Mori, Taeko Hotta, Yuya Kunisaki, Hiroshi Shigeto, Noriko Isobe, Koichi Akashi, Koji Kato","doi":"10.1038/s41409-025-02616-z","DOIUrl":"https://doi.org/10.1038/s41409-025-02616-z","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subsequent cancers following non-myeloablative conditioning for allogeneic hematopoietic cell transplantation.","authors":"Phuong Vo, Kevin Ng, Gary Schoch, Jason Cooper, Abhishek Vupalanchi, Mary Flowers, Brenda M Sandmaier, Ted Gooley, Rainer Storb","doi":"10.1038/s41409-025-02606-1","DOIUrl":"https://doi.org/10.1038/s41409-025-02606-1","url":null,"abstract":"<p><p>We examined the risk of subsequent malignant neoplasms (SMNs) in 1720 patients with hematologic cancers given allogeneic hematopoietic grafts from 03/1998 to 08/2023 after nonmyeloablative conditioning regimens. With a median follow-up of 12 years, the cumulative incidence of SMNs was 17% (95% CI, [15%, 19%]). Most SMNs (n = 543) were non-melanoma skin cancers seen in 208 patients; unfortunately, information on these cancers was not available in the Surveillance, Epidemiology, and End Results (SEER) database for comparison with such tumors in the general population. However, developing non-melanoma skin cancers was statistically significantly associated with chronic GVHD and, thus, unlikely to be conditioning regimen related. Eighty-six patients (5%) developed 93 other SMNs. This number (93 SNMs) significantly exceeded the expected 73.4 cases in the comparison group (p = 0.03). This increase was driven exclusively by increases in uterine adenocarcinoma (n = 2), squamous lip cancer (n = 5), and squamous penile cancer (n = 2); the latter two cancers were, again, associated with chronic GVHD. Apart from these three tumor types, there were no observed increases in the risk of other tumors compared to those in the general population.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-transplant cyclophosphamide, abatacept, and vedolizumab to prevent GVHD after hematopoietic stem cells transplantation in children with acute leukemia: results of a prospective trial.","authors":"M Perminova, L Shelikhova, M Klimentova, Y Skvortsova, D Balashov, M Ilyushina, D Shasheleva, R Khismatullina, I Shipitsina, A Maschan, M Maschan","doi":"10.1038/s41409-025-02566-6","DOIUrl":"https://doi.org/10.1038/s41409-025-02566-6","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Favorable outcomes and the association between dynamic transfusion dependence and IPSS-M in MDS-h and MDS-LB patients undergoing allo-HSCT.","authors":"Wenjing Guo, Jia Li, Hui Wang, Yuping Fan, Tingting Zhang, Yigeng Cao, Wenbin Cao, Aiming Pang, Donglin Yang, Xin Chen, Rongli Zhang, Jialin Wei, Qiaoling Ma, Weihua Zhai, Yi He, Yizhou Zheng, Erlie Jiang, Mingzhe Han, Sizhou Feng","doi":"10.1038/s41409-025-02613-2","DOIUrl":"https://doi.org/10.1038/s41409-025-02613-2","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD28-costimulated CD19 CAR-T cells for pediatric mature non-Hodgkin B-cell lymphoma.","authors":"Alon Abramovich, Etai Adam, Adi Shapira, Daphna Hutt, Orit Itzhaki, Bella Bielorai, Amos Toren, Elad Jacoby","doi":"10.1038/s41409-025-02615-0","DOIUrl":"https://doi.org/10.1038/s41409-025-02615-0","url":null,"abstract":"<p><p>Children with relapsed or refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL) have a poor prognosis with approved therapies. Chimeric antigen receptor (CAR)-T cells are approved for adults with R/R B-NHL, but pediatric data is lacking. We report on 13 children with R/R mature B-NHL enrolled on a clinical trial for CD19 CAR-T cells harboring CD28 costimulation. Twelve patients were infused with CAR-T cells, and one had progressed and died prior to infusion. Toxicities included cytokine release syndrome in 8 patients and neurotoxicity in 6, including two patients with grade 4 neurotoxicity. All patients responded to CAR-T cells, including a complete response in 6, complete metabolic response in 2 and partial response in four. The median event-free survival was 15.2 months and median overall survival was not reached. Outcome differed by disease type, as most patients with primary mediastinal B-cell lymphoma had long term remissions, while only two of seven patients with Burkitt lymphoma were long term survivors. Thus, initial response may suffice for certain patients, but further consolidative strategies should be studied in patients with R/R Burkitt lymphoma.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}