Transplantation and Cellular Therapy最新文献

{"title":"An Extended Flow Cytometry Evaluation of ex Vivo Expanded NK Cells Using K562.Clone1, a Feeder Cell Line Manufactured in Brazil","authors":"","doi":"10.1016/j.jtct.2024.07.004","DOIUrl":"10.1016/j.jtct.2024.07.004","url":null,"abstract":"<div><div>Natural killer (NK) cells play a crucial role in the immune system's response against cancer. However, the challenge of obtaining the required quantity of NK cells for effective therapeutic response necessitates the development of strategies for their ex vivo expansion. This study aimed to develop a novel feeder cell line, K562.Clone1, capable of promoting the ex vivo expansion of NK cells while preserving their cytotoxic potential. he K562 leukemic cell line was transduced with mbIL-21 and 4-1BBL proteins to generate K562.Clone1 cells. NK cells were then co-cultured with these feeder cells, and their expansion rate was monitored over 14 days. The cytotoxic potential of the expanded NK cells was evaluated against acute myeloid leukemia blasts and tumor cell lines of leukemia and glial origin. Statistical analysis was performed to determine the significance of the results. The K562.Clone1 co-cultured with peripheral NK showed a significant increase in cell count, with an approximate 94-fold expansion over 14 days. Expanded NK cells demonstrated cytotoxicity against the tested tumor cell lines, indicating preservation of their cytotoxic characteristics. Additionally, the CD56, CD16, inhibitory KIRs, and activation receptors were conserved and present in a well-balanced manner. The study successfully developed a feeder cell line, K562.Clone1, that effectively promotes the expansion of NK cells ex vivo while maintaining their cytotoxic potential. This development could significantly contribute to the advancement of NK cell therapy, especially in Brazil.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1063.e1-1063.e19"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580929","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":"Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infections after Allogeneic Hematopoietic Stem Cell Transplantation","authors":"Rong Fu ,&nbsp;Jun Xu ,&nbsp;Zhiping Fan ,&nbsp;Hong Qu ,&nbsp;Yirong Jiang ,&nbsp;Wenjie Xiong ,&nbsp;Fen Huang ,&nbsp;Li Xuan ,&nbsp;Na Xu ,&nbsp;Hui Liu ,&nbsp;Zhixiang Wang ,&nbsp;Jing Sun ,&nbsp;Qifa Liu ,&nbsp;Ren Lin","doi":"10.1016/j.jtct.2024.08.014","DOIUrl":"10.1016/j.jtct.2024.08.014","url":null,"abstract":"<div><div>Early and accurate identification of pathogens in pulmonary infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critically important. The clinical usefulness of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary infections after allo-HSCT remains under discussion. This multicenter retrospective study was conducted to compare mNGS and conventional microbiological tests (CMTs) in identifying the pathogens of pulmonary infections in allo-HSCT recipients. One hundred forty allo-HSCT recipients with suspected pulmonary infections who underwent bronchoscopy were included. mNGS and CMTs performed on bronchoalveolar lavage fluid specimens showed 71.4% positivity on mNGS compared to 55.0% positivity on CMTs. mNGS identified 182 pathogens, including bacteria (n = 88), fungi (n = 35) and viruses (n = 59), compared to 106 pathogens detected by CMTs (bacteria, n = 31; fungi, n = 24; viruses, n = 51). Pulmonary infection was finally diagnosed in 98 patients, including 22 bacterial, 7 fungal, 18 viral, and 48 mixed infections and 3 infections with an unknown pathogen. Mixed infections were identified in 50.5% of the patients with pulmonary infection. The sensitivity of mNGS and CMTs for diagnosing pulmonary infections was 88.8% and 69.4%, respectively (<em>P</em> = .001), and the specificity were 81.0% and 85.7%, respectively (<em>P</em> = .688). Our findings suggest that mNGS may be a promising technology for diagnosing pulmonary infections in allo-HSCT recipients.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1110.e1-1110.e10"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093910","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":"CASTing out the demons of graft versus host disease","authors":"Javier Bolaños-Meade","doi":"10.1016/j.jtct.2024.10.006","DOIUrl":"10.1016/j.jtct.2024.10.006","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1045-1046"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586637","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":"Transplant Outcomes in Myelofibrosis: Impact of Donor Type (Cord Blood Grafts Supported by CD34+ selected Cells [Haplo-Cord] Versus Matched Donors)","authors":"Nima Ghalehsari ,&nbsp;Franco Castillo Tokumori ,&nbsp;Zhengming Chen ,&nbsp;Marie Liu ,&nbsp;Sebastian A. Mayer ,&nbsp;Ghaith Abu Zeinah ,&nbsp;Tsiporah B. Shore ,&nbsp;Ellen K. Ritchie ,&nbsp;Richard T. Silver ,&nbsp;Joseph M. Scandura ,&nbsp;Gail J. Roboz ,&nbsp;Koen van Besien ,&nbsp;Alexandra Gomez-Arteaga","doi":"10.1016/j.jtct.2024.08.023","DOIUrl":"10.1016/j.jtct.2024.08.023","url":null,"abstract":"<div><div>Despite the established potentially curative role of allogeneic hematopoietic cell transplantation (allo-HCT) in managing myelofibrosis (MF), the choice of alternative donors for patients lacking matched donors remains a challenge, and the optimal graft source in this disease entity continues to be an ongoing debate. We aimed to evaluate the impact of donor type: umbilical cord blood transplant supported with CD34+ selected haploidentical donor (haplo-cord) versus adult matched related donor (MRD) and matched unrelated donor (MUD) in 40 adult patients with primary or secondary MF, including those progressing to accelerated phase (AP) or blast phase (BP), who underwent their first allo-HCT. The primary objective of this study was to analyze the impact of stem cell source on primary endpoints of overall survival (OS), graft-versus-host disease, and non-relapse mortality (NRM). Median follow-up for all alive patients was 53 months (range 0.3-63 months). Nine patients (22.5%) underwent an MRD allo-HCT, 15 patients (37.5%) underwent a MUD allo-HCT, and 16 patients (40%) underwent a haplo-cord allo-HCT. Four patients died without neutrophil engraftment: 3 (19%) in haplo-cord group and one (4%) in MRD/MUD group. The cumulative incidence of absolute neutrophil engraftment by day 60 was 80% (95% CI 45-94) in the haplo-cord group and 92% (95% CI 65-98) in the MRD/MUD group (<em>P</em> = .09). The cumulative incidence of platelet engraftment by day 60 was 59% (95% CI 27-81) in haplo-cord group and 75% (95% CI 51-88) in MRD/MUD group (<em>P</em> = .4). OS was 62% at 1 year (95% CI 49-79) and 34% at 3 years (95% CI 21-55). The 3-year OS was similar between the haplo-cord group and the MRD/MUD (37% versus 32%, <em>P</em> = .9). The 1-year OS for AP/BP patients was 50% (95% CI 27-93) in the haplo-cord group, compared to 40% (95% CI 19-86) in the MRD/MUD. The 1-year OS for chronic phase CP patients was 83% (95% CI 58-100) in the haplo-cord group, compared to 79% (95% CI 60-100) in the MRD/MUD group. The cumulative incidence of relapse at 3 years in the haplo-cord group was 13% (95% CI 1.8-34), and in the MRD/MUD group was 28% (95% CI 10-49) (<em>P</em> = .36). One-year NRM was 38% (95% CI 15-61) in the haplo-cord group and 33% (95% CI 15-52) in the MRD/MUD group. Three-year NRM was 48% (95% CI 19-72) in the haplo-cord group and 54% (95% CI 29-73) in MRD/MUD group (<em>P</em> = .95). We showed no significant difference in OS, relapse, and NRM outcomes after haplo-cord transplant compared to adult matched donors’ grafts (MRD or MUD) in MF patients. However, there were more graft failures in patients transplanted with a haplo-cord transplants and delayed engraftments with inadequate haplo myeloid bridges. Despite the small sample size in our study, considering our findings and the availability of other alternative donors, using haplo-cord platforms may no longer be justified for MF unless the UCB engraftment dynamics can be optimized.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1100.e1-1100.e11"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146324","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":"Effects of Consolidation Therapy With Autologous Hematopoietic Stem Cell Transplantation After BCMA-CAR T-Cell Therapy on the Survival of Patients With Relapsed or Refractory Multiple Myeloma","authors":"Ziwei Zhou,&nbsp;Xuan Liu,&nbsp;Xuejun Zhang,&nbsp;Shupeng Wen,&nbsp;Huan Hua,&nbsp;Zheng Xu,&nbsp;Fuxu Wang","doi":"10.1016/j.jtct.2024.08.024","DOIUrl":"10.1016/j.jtct.2024.08.024","url":null,"abstract":"<div><div>Despite the success of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory multiple myeloma (RRMM), failure after CAR T-cell therapy remains an unmet medical need. An effective consolidation therapy after CAR T-cell therapy may improve the prognosis of RRMM. To investigate the effects of consolidation therapy with autologous hematopoietic stem cell transplantation (AHCT) after B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy on the prognosis of RRMM patients. This retrospective study included 39 RRMM patients who received BCMA-targeted CAR T-cell therapy. Basic clinical, therapy, and outcome data were collected, and factors associated with survival were analyzed. Among the 39 RRMM patients included in the study, 15 had high-risk cytogenetics and 11 had extramedullary disease (EMD). All 39 patients reached peak CAR T-cell expansion within 28 days after infusion. Twenty-six patients developed cytokine release syndrome, including 12 grade 1 and 14 grade 2 cases. Survival analysis revealed that high-risk cytogenetics, high tumor load (International Staging System [ISS] stage III), and EMD were negatively associated with progression-free survival (PFS) and overall survival (OS). Thirteen patients received consolidation AHCT therapy 50-276 days after CAR T-cell therapy, with a median interval of 92 days. No serious complications occurred after consolidation AHCT. Survival analysis showed that consolidation AHCT effectively improved OS and PFS over maintenance chemotherapy. Moreover, Cox regression analysis identified low tumor load (ISS stage I/II) and consolidation AHCT as independent predictors of superior PFS and OS and high-risk cytogenetics as an independent risk factor for poor PFS. Consolidation AHCT after CAR T-cell therapy in RRMM patients can improve patient survival.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1080.e1-1080.e11"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141204","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":"Dynamic Relapse Prediction by Peripheral Blood WT1mRNA after Allogeneic Hematopoietic Cell Transplantation for Myeloid Neoplasms","authors":"Soichiro Nakako ,&nbsp;Hiroshi Okamura ,&nbsp;Isao Yokota ,&nbsp;Yukari Umemoto ,&nbsp;Mirei Horiuchi ,&nbsp;Kazuki Sakatoku ,&nbsp;Kentaro Ido ,&nbsp;Yosuke Makuuchi ,&nbsp;Masatomo Kuno ,&nbsp;Teruhito Takakuwa ,&nbsp;Mitsutaka Nishimoto ,&nbsp;Asao Hirose ,&nbsp;Mika Nakamae ,&nbsp;Yasuhiro Nakashima ,&nbsp;Hideo Koh ,&nbsp;Masayuki Hino ,&nbsp;Hirohisa Nakamae","doi":"10.1016/j.jtct.2024.08.008","DOIUrl":"10.1016/j.jtct.2024.08.008","url":null,"abstract":"<div><div>Although various relapse prediction models based on pretransplant information have been reported, they cannot update the predictive probability considering post-transplant patient status. Therefore, these models are not appropriate for deciding on treatment adjustment and preemptive intervention during post-transplant follow-up. A dynamic prediction model can update the predictive probability by considering the information obtained during follow-up. This study aimed to develop and assess a dynamic relapse prediction model after allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using peripheral blood Wilms’ tumor 1 messenger RNA (WT1mRNA). We retrospectively analyzed patients with AML or MDS who underwent allo-HCT at our institution. To develop dynamic models, we employed the landmarking supermodel approach, using age, refined disease risk index, conditioning intensity, and number of transplantations as pretransplant covariates and both pre- and post-transplant peripheral blood WT1mRNA levels as time-dependent covariates. Finally, we compared the predictive performances of the conventional and dynamic models by area under the time-dependent receiver operating characteristic curves. A total of 238 allo-HCT cases were included in this study. The dynamic model that considered all pretransplant WT1mRNA levels and their kinetics showed superior predictive performance compared to models that considered only pretransplant covariates or factored in both pretransplant covariates and post-transplant WT1mRNA levels without their kinetics; their time-dependent areas under the curve were 0.89, 0.73, and 0.87, respectively. The predictive probability of relapse increased gradually from approximately 90 days before relapse. Furthermore, we developed a web application to make our model user-friendly. This model facilitates real-time, highly accurate, and personalized relapse prediction at any time point after allo-HCT. This will aid decision-making during post-transplant follow-up by offering objective relapse forecasts for physicians.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1088.e1-1088.e12"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988991","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":"Efficacy of a Modified Post-Transplant Cyclophosphamide Regimen for Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients with Severe Aplastic Anemia: A Prospective Study","authors":"Xiaowei Chen ,&nbsp;Cunte Chen ,&nbsp;Ming Zhou,&nbsp;Yuling Zhang,&nbsp;Caixia Wang,&nbsp;Yumiao Li,&nbsp;Ruiqing Zhou,&nbsp;Shilin Xu,&nbsp;Wei Zhou,&nbsp;Tingfen Deng,&nbsp;Shiyi Pan,&nbsp;Liangliang Wu,&nbsp;Yuping Zhang,&nbsp;Wenjian Mo ,&nbsp;Shunqing Wang","doi":"10.1016/j.jtct.2024.08.016","DOIUrl":"10.1016/j.jtct.2024.08.016","url":null,"abstract":"<div><div>The aim of the present study was to examine the efficacy of the modified post-transplant cyclophosphamide (PTCy) regimen, which involved reducing the Cy dose to 40 mg on days +3 and +4 in patients with severe aplastic anemia (SAA) subjected to unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT). For this purpose, a prospective single-center trial was conducted and the clinical outcomes were collected from 30 patients with SAA treated with the modified PTCy regimen for URD-HSCT. The median time to neutrophil and platelet engraftment was 13 days (range, 11 to 16) and 12 days (range, 5 to 33), respectively. The cumulative incidence of neutrophil and platelet engraftment was 93.1% ± 0.3% and 96.6% ± 0.2%, respectively. The 2-year overall survival (OS) was 97% (95% confidence interval [CI]: 90%-100%] and 2-year graft-versus-host disease (GVHD) and rejection-free survival (GRFS) was 93% (95% CI: 85%-100%). The incidence rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were 13.8 ± 0.4% and 10.3 ± 0.3%, respectively, and no patients developed grades III-IV aGVHD. However, only one patient developed a moderate extensive cGVHD. The incidence of reconstitution varies among different subsets of immune cells after URD-HSCT. Natural killer (NK) cells recover first, followed by CD8⁺ T and CD19⁺ B cells, and finally CD4⁺ T cells. In conclusion, the present study demonstrates that the modified PTCy regimen, with a reduced dose of 40 mg on days +3 and +4, may be an effective regimen for URD-HSCT in patients with SAA and reduce the occurrence of the GVHD.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1099.e1-1099.e10"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073940","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":"Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma","authors":"Frederick L. Locke ,&nbsp;Sattva S. Neelapu ,&nbsp;Nancy L. Bartlett ,&nbsp;Lazaros J. Lekakis ,&nbsp;Caron A. Jacobson ,&nbsp;Ira Braunschweig ,&nbsp;Olalekan O. Oluwole ,&nbsp;Tanya Siddiqi ,&nbsp;Yi Lin ,&nbsp;John M. Timmerman ,&nbsp;Marie José Kersten ,&nbsp;Yan Zheng ,&nbsp;Teresa Zhang ,&nbsp;Jenny Nater ,&nbsp;Rhine Shen ,&nbsp;Harry Miao ,&nbsp;Jenny J. Kim ,&nbsp;David B. Miklos","doi":"10.1016/j.jtct.2024.08.018","DOIUrl":"10.1016/j.jtct.2024.08.018","url":null,"abstract":"<div><div>Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell–related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort 3 and received conditioning chemotherapy on d −5 through −3 followed by a single infusion of axi-cel (2 × 10⁶ cells/kg) on d 0. Prophylactic tocilizumab (8 mg/kg) was administered 48 h after axi-cel infusion. Primary endpoints were incidence and severity of CRS and NEs. Key secondary endpoints included the incidence of adverse events, objective response rate (ORR), duration of response, progression-free survival, overall survival (OS), and biomarker analyses (eg, circulating CAR T cells, cytokines, chemokines). Forty-two patients were enrolled in Cohort 3, 38 of whom received axi-cel. In the 24-month analysis, any-grade CRS and NEs occurred in 92% and 87% of patients, and Grade ≥3 CRS and NEs occurred in 3% and 42% of patients, respectively. One Grade 5 NE (cerebral edema) occurred. With 24-mo minimum follow-up, the ORR was 63%, and 39.5% of patients had ongoing response. With 48-month follow-up, median OS was 34.8 mo (95% CI, 5.4–not estimable). CAR T-cell expansion in ZUMA-1 Cohort 3 was comparable with pivotal Cohorts 1 and 2. Consistent with tocilizumab-mediated inhibition of IL-6R, serum IL-6 levels were increased relative to Cohorts 1 and 2. Grade ≥3 NEs were associated with elevated IL-6 levels, proinflammatory cytokines, and myeloid cells in the cerebrospinal fluid. Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell–related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1065-1079"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073942","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":"CAST Regimen for GvHD Prophylaxis: A CIBMTR Propensity Score-Matched Analysis","authors":"A Samer Al-Homsi ,&nbsp;Todd E. DeFor ,&nbsp;Kelli Cole ,&nbsp;Frank Cirrone ,&nbsp;Stephanie King ,&nbsp;Andres Suarez-Londono ,&nbsp;George Yaghmour ,&nbsp;Stephanie Boisclair ,&nbsp;Caitrin Bupp ,&nbsp;Stephen R. Spellman","doi":"10.1016/j.jtct.2024.08.015","DOIUrl":"10.1016/j.jtct.2024.08.015","url":null,"abstract":"<div><div>Previously, we reported excellent results with the combination of post-transplant cyclophosphamide (PTCy), abatacept, and a short course of tacrolimus (CAST) for the prevention of graft-versus-host disease (GvHD) following peripheral blood haploidentical transplantation. To further substantiate these results, we performed a propensity score-matched analysis. Patients enrolled in the CAST trial were matched with patients from a contemporaneous cohort from the Center for International Blood and Marrow Transplant Research database who received PTCy, tacrolimus, and mycophenolate mofetil, using nearest neighbor propensity score matching. An excellent balance between pairs was achieved as measured by the density distribution and standardized differences of covariates (median 0.09). The rates of acute GvHD grades II to IV at day +120 and 1-year GvHD- and relapse-free survival were 16.7% and 66.7% in the CAST cohort versus 28.6% and 47.6% in the control group, respectively. This trend did not reach statistical significance (<em>P</em> = .14 and .07), possibly due to the small numbers of patients and events. On the other hand, CAST was associated with a statistically significant reduction in the incidence of relapse (9.5% versus 26.2%, <em>P</em> = .045) with improved disease-free survival (85.7% versus 61.9%, <em>P</em> = .01). Our data provides a strong impetus to examine CAST in a randomized clinical trial.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1092-1098"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112362","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 Analysis of Barriers to Timely Administration of Chimeric Antigen Receptor T Cell (CAR T) Therapy in Diffuse Large B-cell Lymphoma","authors":"Bei Hu ,&nbsp;Rakhee Vaidya ,&nbsp;Ferdous Ahmed ,&nbsp;Hamid Ehsan ,&nbsp;Tamara K Moyo ,&nbsp;Ryan W Jacobs ,&nbsp;Yifan Pang ,&nbsp;Steven Park ,&nbsp;Michelle L Wallander ,&nbsp;Vishal Shroff ,&nbsp;Victoria Boseman ,&nbsp;Travis Beam ,&nbsp;Jennifer Elder ,&nbsp;Melissa Yountz ,&nbsp;Rebecca D Jennings ,&nbsp;Dianna S Howard ,&nbsp;Belinda Avalos ,&nbsp;Edward A Copelan ,&nbsp;Ruben Mesa ,&nbsp;Nilanjan Ghosh","doi":"10.1016/j.jtct.2024.09.007","DOIUrl":"10.1016/j.jtct.2024.09.007","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The implementation of chimeric antigen receptor T (CAR T) therapy in the real-world setting is hindered by logistical and financial barriers, impacting timely access to this life-saving treatment. Clinical trials have reported the time from leukapheresis to CAR T cell infusion (vein-to-vein time) but not the time from CAR T referral to infusion (decision-to-vein time). Herein, we report the barriers to CAR T therapy in a real-world setting. We evaluated the factors influencing the decision-to-vein time and explored the association with clinical outcomes in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who received CAR T therapy. We conducted a retrospective study of adult patients with relapsed/refractory DLBCL who underwent consultation for CAR T cell therapy at Levine Cancer Institute and Wake Forest Comprehensive Cancer Center and collected information regarding demographic data, referral type, insurance type, CAR T product, and survival outcomes. The effects of variables on decision-to-vein time were analyzed by Fisher's exact test for categorial variables and Wilcoxon rank-sum test for continuous variables. Survival analyses were performed using Kaplan–Meier and Cox Proportional Hazard models. The study included 142 patients who were referred for CAR T of which 99 patients received CAR T. Median decision-to-vein time was 62 days compared to median vein-to-vein time of 32 days. Patients with private insurance took longer to obtain financial clearance compared to patients with government insurance (median 25 versus 9 days, &lt;em&gt;P&lt;/em&gt; &lt; .001). Of those with private insurance (&lt;em&gt;n&lt;/em&gt; = 63), 35% needed a single-case agreement (SCA) which led to significant delay in receiving financial clearance (median 50.5 versus 19 days, &lt;em&gt;P&lt;/em&gt; &lt; .001) and increased decision-to-vein time (median 75 versus 55 days, &lt;em&gt;P&lt;/em&gt; &lt; .001) compared to those who did not need SCA. Decision-to-vein time was significantly different among various products, clinical trial being the shortest (median 47 days, &lt;em&gt;n&lt;/em&gt; = 9) and non-conforming products being the longest (median 94.5 days, &lt;em&gt;n&lt;/em&gt; = 6) (&lt;em&gt;P&lt;!--&gt; &lt;/em&gt;&lt; .001). Axi-cel had the shortest median decision-to-vein time at 61 days compared to 81 days with tisa-cel and 85 days with liso-cel. Although delays in receiving CAR T therapy did not impact survival, the median overall survival for patients who were referred for CAR T therapy but did not receive it, was significantly lower than those who received CAR T cell therapy (9.0 versus 21.0 months, &lt;em&gt;P&lt;/em&gt; &lt; .001). Decision-to-vein time is a major cause of delay in receiving CAR T therapy. SCAs lead to significant increase in decision-to-vein time leading to delays in CAR T therapy in a real-world setting. Patients who were referred for CAR T but are not able to receive it, have inferior survival compared to CAR T recipients. Our findings underscore the significance of addressing administrative hurdle","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1082.e1-1082.e10"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269263","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}