Marta Canelo-Vilaseca, Mohamad Sabbah, Roberta Di Blasi, Caterina Cristinelli, Anna Sureda, Sophie Caillat-Zucman, Catherine Thieblemont
{"title":"Lymphodepletion chemotherapy in chimeric antigen receptor-engineered T (CAR-T) cell therapy in lymphoma","authors":"Marta Canelo-Vilaseca, Mohamad Sabbah, Roberta Di Blasi, Caterina Cristinelli, Anna Sureda, Sophie Caillat-Zucman, Catherine Thieblemont","doi":"10.1038/s41409-025-02539-9","DOIUrl":"10.1038/s41409-025-02539-9","url":null,"abstract":"The development of chimeric antigen receptor (CAR) T-cells, engineered from peripheral T-lymphocytes of a patient with lymphoma, in order to specifically target tumor cells, has been a revolution in adoptive cell therapy (ACT). As outlined in this review, ACT was initiated by hematopoietic cell transplantation (HSCT) and re-injection of interleukin-boosted tumor-infiltrating lymphocytes (TIL). The innovative venture of genetically modifying autologous peripheral T-cells to target them to cell-surface tumoral antigens through an antibody-derived structure (i.e. independent of major histocompatibility antigen presentation, physiologically necessary for T-cell activation), and intracytoplasmic T-cell costimulatory peptides, via a novel membrane CAR, has been an outstanding breakthrough. Here, focusing on B-cell hematological malignancies and mostly non-Hodgkin lymphoma, attention is brought to the importance of providing an optimal microenvironment for such therapeutic cells to proliferate and positively develop anti-tumoral cytotoxicity. This, perhaps paradoxically, implies a pre-infusion step of deep lymphopenia and deregulation of immunosuppressive mechanisms enhanced by tumoral cells. Fludarabine and cyclophosphamide appear to be the most efficient lymphodepletive drugs in this context, dosage being of importance, as will be illustrated by a thorough literature review.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"559-567"},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41409-025-02539-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhagirathbhai Dholaria, Shakthi T Bhaskar, Vivek G Patel, Eden Biltibo, Reena Jayani, Salyka Sengsayadeth, Andrew Jallouk, James Jerkins, Brittney Baer, Ali Nur, Muhamed Baljevic, Bipin N Savani, David Morgan, Adetola A Kassim, Olalekan O Oluwole
{"title":"Feasibility of axicabtagene ciloleucel in the outpatient setting: primary analysis of prospective trial.","authors":"Bhagirathbhai Dholaria, Shakthi T Bhaskar, Vivek G Patel, Eden Biltibo, Reena Jayani, Salyka Sengsayadeth, Andrew Jallouk, James Jerkins, Brittney Baer, Ali Nur, Muhamed Baljevic, Bipin N Savani, David Morgan, Adetola A Kassim, Olalekan O Oluwole","doi":"10.1038/s41409-025-02551-z","DOIUrl":"10.1038/s41409-025-02551-z","url":null,"abstract":"<p><p>The pivotal trials of axicabtagene ciloleucel (axi-cel) chimeric Antigen receptor (CAR-T) therapy and other CD19 CAR-Ts were mainly done in the inpatient setting. We conducted a single-center non-randomized open label prospective clinical trial (NCT05108805). Objective was to evaluate the feasibility and safety of outpatient administration of axi-cel for relapsed/refractory diffuse B cell lymphoma (R/R DLBCL) using continuous remote patient monitoring with wearable devices and telemedicine. We enrolled 25 and treated 20 patients on this clinical trial from November 2021 to October 2023. The median follow up was 374 days (95% CI: 364-484). The median age was 69 years and 18 of 20 patients (90%) received prophylactic corticosteroids. Nineteen patients got admitted for management of cytokine release syndrome (CRS) in the first 4 weeks. The median duration of hospital stay was 5.5 days (range: 0-21). Two patients required ICU stay due to pre-existing conditions exacerbated by CRS. Grade 2 CRS was seen in 40% and no pt had grade ≥3 CRS. Grade 3 Immune effector cell-associated neurotoxicity syndrome (ICANS) was seen in 20% and none had grade ≥4 ICANS. No treatment-related death by last follow-up. The results of our pilot study confirm the feasibility of outpatient administration of axi-cel.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699682","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}
Nicole Santoro, Christoph Schmid, Moniek de Witte, Mieke W. H. Roeven, Victoria Potter, Deborah Richardson, Thomas Schroeder, Veronika Válková, Katherine Clesham, Sandrine Loron, Jakob Passweg, Caroline Besley, Bernd Gruhn, Jorinde D. Hoogenboom, Jarl E. Mooyaart, Isabel Sanchez-Ortega, Simona Pagliuca, Federico Simonetta, Giorgia Battipaglia, Thierry Guillaume, Mette D. Hazenberg, Florent Malard, Jürgen Kuball, Annalisa Ruggeri
{"title":"Current use of donor lymphocyte infusions after allogenic stem cell transplantation in Europe: a survey on behalf of the cellular therapy and immunobiology working party of the EBMT","authors":"Nicole Santoro, Christoph Schmid, Moniek de Witte, Mieke W. H. Roeven, Victoria Potter, Deborah Richardson, Thomas Schroeder, Veronika Válková, Katherine Clesham, Sandrine Loron, Jakob Passweg, Caroline Besley, Bernd Gruhn, Jorinde D. Hoogenboom, Jarl E. Mooyaart, Isabel Sanchez-Ortega, Simona Pagliuca, Federico Simonetta, Giorgia Battipaglia, Thierry Guillaume, Mette D. Hazenberg, Florent Malard, Jürgen Kuball, Annalisa Ruggeri","doi":"10.1038/s41409-025-02555-9","DOIUrl":"10.1038/s41409-025-02555-9","url":null,"abstract":"Unmanipulated donor lymphocyte infusions (DLI) are crucial for enhancing the graft versus tumor (GVT) effect in post-transplant settings. Practices regarding DLI use vary widely among centers, encompassing differences in indications, prerequisites, and application methods. To explore current DLI policies, we developed a comprehensive survey that garnered responses from 165 EBMT centers across 43 countries. Notably, 97% of respondents reported using DLI in their practices. Indications for DLI included preemptive use for minimal residual disease (MRD) positivity in 86.9% of centers and mixed chimerism in 73.1%; therapeutic use for hematological relapse in 73.1%; and prophylactic use for high-risk disease in 43.8%. Active graft-versus-host disease (GVHD) and active infections were deemed absolute contraindications by 85.6% and 57.5% of centers, respectively. 35% of centers did not consider a prior history of acute (a)GVHD as an exclusion criterion. The majority (71.9%) requested immunosuppression withdrawal before DLI. Most centers (71.3%) collected DLI post-transplant, with 78.1% utilizing unstimulated apheresis. The cell doses applied at the first DLI varied significantly, depending on indication, timing, and donor type. This survey provides the largest overview of current DLI practices, highlighting the need for high-quality data to assess the risks and benefits of different approaches.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"697-701"},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691005","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}
José Luis Piñana, Mireia Micó-Cerdà, Dolores Gómez, Ariadna Pérez, Juan Montoro, Rafael Hernani, Pedro Chorão, Juan Carlos Hernández-Boluda, David Navarro, Carlos Solano
{"title":"Early ribavirin reduce RSV symptoms duration in post-allogeneic stem cell transplant: challenges in symptoms duration assessment","authors":"José Luis Piñana, Mireia Micó-Cerdà, Dolores Gómez, Ariadna Pérez, Juan Montoro, Rafael Hernani, Pedro Chorão, Juan Carlos Hernández-Boluda, David Navarro, Carlos Solano","doi":"10.1038/s41409-025-02549-7","DOIUrl":"10.1038/s41409-025-02549-7","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"740-742"},"PeriodicalIF":4.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676707","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}
Emily Limerick, Matthew M. Hsieh, Mauricio Barretto, Neal Jeffries, Clarissa Diamantidis, Yuliya Lokhnygina, Ritika Menon, Santosh L. Saraf, Courtney D. Fitzhugh
{"title":"Kidney function after nonmyeloablative hematopoietic cell transplant for sickle cell disease","authors":"Emily Limerick, Matthew M. Hsieh, Mauricio Barretto, Neal Jeffries, Clarissa Diamantidis, Yuliya Lokhnygina, Ritika Menon, Santosh L. Saraf, Courtney D. Fitzhugh","doi":"10.1038/s41409-025-02550-0","DOIUrl":"10.1038/s41409-025-02550-0","url":null,"abstract":"Hematopoietic cell transplantation (HCT) is potentially curative for patients with sickle cell disease (SCD). Both SCD and HCT cause kidney damage. This study analyzed data from 160 patients who received nonmyelablative HCT for SCD. Renal function was assessed at baseline and annually for 3years. The rate of new-onset eGFR <60 ml/min/1.73m2 was low (2.8%). Rapid kidney function decline in the first year post-HCT was noted in 7.5% of patients but was not associated with subsequently worse renal function. The eGFR decreased post-HCT (1 year: –7.19 p < 0.0001, 2 year: –11.32 p < 0.0001, 3 year: -12.37 ml/min/1.73m2 p < 0.0001). Mean eGFR remained within normal limits throughout the follow-up period (1 year:119, 2 year:115, 3 year:113 ml/min/1.73m2). Hyperfiltration rates decreased with a corresponding increase in patients with normal eGFR post-HCT. Therefore, the decline in eGFR after HCT may represent preservation of renal function. The prevalence of kidney damage increased transiently but, by 3 years post-HCT, was not significantly changed from baseline. Most cases of kidney damage were due to albuminuria. AKI, noted early post-HCT in 39% of patients, was most commonly stage 1 and was associated with decreased survival (p = 0.03). Larger studies with longer follow-up are required to explore the effects of HCT on renal function in patients with SCD.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"690-696"},"PeriodicalIF":4.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691049","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}
Tatum N. Storck, Linde M. Morsink, Anouschka Biswana, Carin L. E. Hazenberg, Gerwin Huls, Goda Choi
{"title":"Donor lymphocyte infusions after HLA-identical hematopoietic stem cell transplantation with post-transplant cyclophosphamide in acute myeloid leukemia patients","authors":"Tatum N. Storck, Linde M. Morsink, Anouschka Biswana, Carin L. E. Hazenberg, Gerwin Huls, Goda Choi","doi":"10.1038/s41409-025-02552-y","DOIUrl":"10.1038/s41409-025-02552-y","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"737-739"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662459","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}
Katharina Kleinschmidt, Gina Penkivech, Anja Troeger, Juergen Foell, Tarek Hanafee-Alali, Stefanie Leszczak, Marcus Jakob, Sonja Kramer, Silke Kietz, Petra Hoffmann, Claudia Behrendt-Böhm, Carina Kaess, Andreas Brosig, Robert Offner, Daniel Wolff, Selim Corbacioglu
{"title":"αß T-cell depleted haploidentical stem cell transplantation for pediatric and young adult patients with transfusion-dependent thalassemia","authors":"Katharina Kleinschmidt, Gina Penkivech, Anja Troeger, Juergen Foell, Tarek Hanafee-Alali, Stefanie Leszczak, Marcus Jakob, Sonja Kramer, Silke Kietz, Petra Hoffmann, Claudia Behrendt-Böhm, Carina Kaess, Andreas Brosig, Robert Offner, Daniel Wolff, Selim Corbacioglu","doi":"10.1038/s41409-025-02546-w","DOIUrl":"10.1038/s41409-025-02546-w","url":null,"abstract":"Life expectancy of patients with severe transfusion-dependent beta-thalassemia (TDT) remains below that of the general population. Allogenic hematopoietic stem cell transplantation (HSCT) is the standard curative treatment. Due to the paucity of matched donor (MD) availability, haploidentical HSCT (haplo-HSCT) is a reasonable alternative. Twenty patients with TDT (median age 10 years; range 2–23) received either a matched sibling donor (MSD; n = 7) or a haplo-HSCT (n = 13) in a single center (Regensburg, Germany) between 2016 and 2022, including two patients referred for a haplo-HSCT as rescue failing prior MD- and haplo-HSCT, respectively. The conditioning regimen consisted of anti-thymocyte globulin (ATG; Grafalon®), treosulfan, thiotepa, and fludarabine (FTT). Immunosuppression consisted of a calcineurin inhibitor and mycophenolate mofetil (MMF). At a median follow-up of 37 months (range 6–90), overall survival (OS) was 100% with a disease-free survival (DFS) of 100% in MSD and 92% in haplo-HSCT, respectively. Two patients in haplo-HSCT experienced graft failure, one achieving DFS after a second haplo-HSCT. No acute graft-versus-host disease (aGvHD) ≥ °III or severe chronic GvHD (cGvHD) were observed. No sinusoidal obstruction syndrome (SOS) was observed in this high-risk population. Treosulfan-based T-cell depleted haplo-HSCT can achieve comparable OS and DFS even in young adult TDT patients with no SOS/VOD.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"682-689"},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41409-025-02546-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. H. G. Stuut, C. Nijssen, L. van der Wagen, A. van Rhenen, L. G. M. Daenen, A. Janssen, F. A. Verheij, I. Brinkman, F. M. Verduyn Lunel, H. Koene, R. Fijnheer, H. J. Prins, K. Westinga, J. Drylewicz, J. Kuball, M. A. de Witte
{"title":"Improved GVHD-free and relapse-free survival after ex vivo αβTCR and CD19 depleted allogeneic HSCT compared to T cell replete HSCT","authors":"A. H. G. Stuut, C. Nijssen, L. van der Wagen, A. van Rhenen, L. G. M. Daenen, A. Janssen, F. A. Verheij, I. Brinkman, F. M. Verduyn Lunel, H. Koene, R. Fijnheer, H. J. Prins, K. Westinga, J. Drylewicz, J. Kuball, M. A. de Witte","doi":"10.1038/s41409-025-02538-w","DOIUrl":"10.1038/s41409-025-02538-w","url":null,"abstract":"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) aims to cure patients without inducing severe graft-versus-host disease (GVHD) or relapse. In prospective studies of mostly pediatric patients with haploidentical donors, ex vivo αβTCR/CD19 depletion has shown to have low incidences of GVHD, but data for adults with matched related (MRD) or unrelated donors (MUD) remain limited. We analyzed the outcomes of recipients who received a myeloablative regimen plus ATG, followed by an αβTCR/CD19-depleted allograft (cohort D+ATG (n = 122)), and compared outcomes to T cell-replete cohorts (cohort R (N = 60)); without ATG; R+ATG = with ATG (N = 129) in a single-center retrospective analysis. In D+ATG, the incidence of aGVHD grade III–IV was 7%, compared to 13% in R and 16% in R+ATG (p = 0.09). Extensive cGVHD was reduced from 23% in R and 10% in R+ATG to 2% in D+ATG (p < 0.001). The reduced incidence of cGVHD led to a superior GVHD-relapse-free survival (GRFS) of 56.7% in D+ATG versus 36.7% in R and 42.8% in R+ATG (p = 0.03) at 2 years. In conclusion, the combination of myeloablative conditioning, ATG, and ex vivo αβTCR/CD19 depletion appears to be a promising approach to enhance GRFS in adult patients up to 75 years of age undergoing allo-HSCT.","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"673-681"},"PeriodicalIF":4.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633561","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}
Osama Ahmad, Nicolaus Kröger, Eva Wagner-Drouet, David Nachbaur, Normann Steiner, Daniel Teschner, Sabrina Kraus, Gesine Bug, Salem Ajib, Johannes Schetelig, Wolfgang Andreas Bethge, Thomas Schroeder, Judith Schaffrath, Lutz Peter Müller, Mareike Verbeek, Edgar Jost, Hatice Soysal, Johanna Tischer, Georg-Nikolaus Franke, Stefan Klein, Udo Holtick, Knut Wendelin, Claudia Lengerke, Martin Bornhäuser, Jan Frederic Weller, Maximilian Christopeit, on behalf of the German Cooperative Transplant Study Group
{"title":"Allogeneic hematopoietic cell transplantation after infection with SARS-CoV-2 during the COVID-19 pandemic: a multicenter retrospective analysis","authors":"Osama Ahmad, Nicolaus Kröger, Eva Wagner-Drouet, David Nachbaur, Normann Steiner, Daniel Teschner, Sabrina Kraus, Gesine Bug, Salem Ajib, Johannes Schetelig, Wolfgang Andreas Bethge, Thomas Schroeder, Judith Schaffrath, Lutz Peter Müller, Mareike Verbeek, Edgar Jost, Hatice Soysal, Johanna Tischer, Georg-Nikolaus Franke, Stefan Klein, Udo Holtick, Knut Wendelin, Claudia Lengerke, Martin Bornhäuser, Jan Frederic Weller, Maximilian Christopeit, on behalf of the German Cooperative Transplant Study Group","doi":"10.1038/s41409-025-02548-8","DOIUrl":"10.1038/s41409-025-02548-8","url":null,"abstract":"","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":"60 5","pages":"733-736"},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41409-025-02548-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
