Transplantation and Cellular Therapy最新文献

{"title":"Letermovir for prevention of recurrent CMV in high-risk allogeneic hematopoietic cell transplant (HCT) recipients.","authors":"Gyuri Han, Anat Stern, Yeon Joo Lee, Yuxuan Li, Parastoo B Dahi, Roni Tamari, Boglarka Gyurkocza, Ann A Jakubowski, Esperanza B Papadopoulos, Brian Shaffer, Miguel-Angel Perales, Karam M Obeid, Jo-Anne H Young, Genovefa A Papanicolaou","doi":"10.1016/j.jtct.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.010","url":null,"abstract":"<p><strong>Background: </strong>We evaluated letermovir (LTV) for secondary prophylaxis for cytomegalovirus (CMV) in allogeneic hematopoietic cell transplant recipients (HCT) at high-risk for CMV recurrence.</p><p><strong>Methods: </strong>Open-label study conducted at Memorial Sloan Kettering Cancer Center and the University of Minnesota. Patients with clinically significant CMV infection (cs-CMVi) and ≥1 high-risk criteria for CMV who achieved viral suppression with standard CMV antivirals, received letermovir (LTV) secondary prophylaxis for up to 14 weeks. The primary endpoint was cs-CMVi at week 14. Secondary endpoints included, LTV resistance, CMV end-organ disease (EOD), CMV-related death and LTV related Adverse Events (AE) at week 14.</p><p><strong>Results: </strong>Thirty-six patients were analyzed (CMV seropositive 33, T-cell depleted HCT 25, cord blood allograft 5) were analyzed. By week 14, 5 patients met the primary endpoint of cs-CMVi, for a cumulative incidence of 14.9% (95% confidence interval 2.6 - 27.1). Four patients developed LTV breakthrough cs-CMVi (including 2 patients with confirmed LTV resistance). The remaining patient developed rebound cs-CMVI after premature discontinuation of LTV due to enrollment in a clinical trial. There were no cases of CMV EOD or CMV-related deaths or LTV related AE by week 14 or by week 24.</p><p><strong>Conclusions: </strong>Our data supports that LTV secondary prophylaxis is safe and effective in high-risk HCT recipients.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865548","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":"Lipid levels increase to the normal range after nonmyeloablative hematopoietic cell transplantation for sickle cell disease.","authors":"Jackie Queen, Emily Limerick, Neal Jeffries, Matthew M Hsieh, Robert D Shamburek, Courtney D Fitzhugh","doi":"10.1016/j.jtct.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.008","url":null,"abstract":"<p><strong>Background: </strong>Individuals with sickle cell disease (SCD) have a unique type of dyslipidemia characterized by low total cholesterol (TC), low low-density lipoprotein cholesterol (LDL-c), low high-density lipoprotein cholesterol (HDL-c), and normal triglycerides (TG). This lipid state is theorized to be cardioprotective against atherosclerosis. In SCD, hematopoietic cell transplant (HCT) offers a potentially curative therapy. Long-term survivors of HCT for hematologic malignancies are at increased risk for dyslipidemia and atherosclerosis long-term. The effects of HCT on SCD dyslipidemia are unknown.</p><p><strong>Objective: </strong>This retrospective cohort study characterizes lipid profiles at baseline and after nonmyeloablative allogeneic HCT for SCD.</p><p><strong>Study design: </strong>We analyzed data from 116 patients after nonmyeloablative HLA-matched sibling or haploidentical HCT for SCD at the NIH from 2009 to 2021. Total cholesterol, HDL-c, LDL-c, and TG were collected pre-HCT, one year post-HCT, and annually thereafter. Data were analyzed using linear generalized estimating equation regression modeling.</p><p><strong>Results: </strong>Successful HCT was associated with a rise in TC, LDL-c, and HDL-c and a decline in TG post-HCT. After HCT, previously low lipid levels increased to the normal range. These changes occurred within the first year of HCT and were maintained thereafter. In patients with graft failure, TC and LDL-c levels remain unchanged from their pre-HCT baseline. Sirolimus use for graft versus host disease prophylaxis was associated with higher TG levels.</p><p><strong>Conclusions: </strong>These findings suggest that SCD dyslipidemia resolves with reversal of the SCD phenotype. The normalization of lipid parameters suggests SCD patients are not at increased risk for atherosclerosis after successful HCT compared to their peers; further studies with longer follow-up are required.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865565","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 I. Phases of Chronic GVHD, Supportive Care, and Systemic Therapy Discontinuation.","authors":"Neel S Bhatt, Andrew C Harris, Lev Gorfinkel, Katarzyna Ibanez, Eric R Tkaczyk, Sandra A Mitchell, Stacey Albuquerque, Tal Schechter, Steven Pavletic, Christine N Duncan, Seth J Rotz, Kirsten Williams, Paul A Carpenter, Geoffrey D E Cuvelier","doi":"10.1016/j.jtct.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.011","url":null,"abstract":"<p><p>Current literature lacks details on the impact of pediatric chronic graft-versus-host disease (cGVHD) on long-term survivorship after allogeneic hematopoietic cell transplantation (HCT). Nonetheless, cGVHD remains a leading cause of post-transplant morbidity and mortality in children and adolescents, which is particularly relevant given the longer life-expectancy after HCT (measured in decades) compared to older adults. To address this knowledge gap, leaders of the Pediatric Transplant and Cellular Therapy Consortium convened a multidisciplinary taskforce of experts in pediatric cGVHD and HCT late effects known as RESILIENT after Chronic GVHD (Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD). Our goals were to define: (1) the current state of understanding about how cGVHD impacts long-term survivorship in children transplanted <18 years of age; (2) practical aspects of care to help clinicians managing long-term pediatric cGVHD survivors; and (3) develop a research framework for the next decade to further our knowledge. Four working groups were formed, each tasked with addressing a unique theme: (1) cGVHD natural history (phases of cGVHD) and its impact on clinicians' ability to taper and durably discontinue systemic therapy; (2) organ dysfunction and immune reconstitution in relation to survivorship; (3) how cGVHD and its treatment impact growth, metabolism, and development in children; and (4) psychosocial health and patient reported outcomes. The four groups met before the 2024 BMT Tandem Meeting in San Antonio, Texas, and then convened a larger in-person RESILIENT conference held on February 20, 2024, at the Tandem meeting to put forth recommendations from their respective working groups and garner feedback. These recommendations are now presented in a series of 4 manuscripts. This current manuscript focuses on the first theme and discusses the phases of cGVHD, challenges in differentiating clinically active from quiescent cGVHD in clinical practice, and the resultant difficulties in determining when and if to taper systemic therapy. To overcome these challenges, we propose revised categorization of long-term cGVHD outcomes and practical recommendations for clinicians and researchers around the long-term follow-up for these patients, including determining when and if to taper systemic therapy, along with the integration of non-immunosuppressive supportive care interventions.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865584","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":"Health-related values discussions with patients undergoing allogeneic and autologous stem cell transplant: Feasibility and acceptability of an early primary palliative care intervention.","authors":"Abigail G Cohen, Christina Cho, Emily Patterson, Jessica Magaldi, Tara Doga, Kristine Naputo, Kelsey Alvarez, Elizabeth Giles, Grace Yang, Afshana Hoque, Dana Kramer, Sean Devlin, David Nemirovsky, William E Rosa, Jessica I Goldberg, Miguel-Angel Perales, Andrew S Epstein, Judith E Nelson, Heather Landau","doi":"10.1016/j.jtct.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.009","url":null,"abstract":"<p><strong>Background: </strong>Hematopoietic stem cell transplant (HSCT) has curative potential but also relatively high morbidity and mortality. Patients have multidimensional palliative care (PC) needs throughout the transplant process. However, PC is not routinely offered to patients with hematologic malignancies. National guidelines recommend PC concurrent with curative hematologic disease treatment, including HSCT.</p><p><strong>Objectives: </strong>Our goal was to determine the feasibility and acceptability of incorporating early and ongoing discussions of patients' core health-related values (HRVs) for patients with hematologic malignancies undergoing HSCT.</p><p><strong>Study design: </strong>We designed and implemented a pilot study evaluating the transplant team's use of a brief, structured guide with eight open-ended questions to support patients' articulation of their HRVs. All English-speaking patients undergoing HSCT from March 2021 to March 2022 in two outpatient HSCT clinics were eligible and offered enrollment. HRV discussions were planned pre-transplant, and then at 5 time points post-transplant (Day 10-14, Day 30, Day 100, 6 months, 1 year). Clinicians and patients were surveyed to assess the feasibility and acceptability of this primary PC intervention.</p><p><strong>Results: </strong>31 patients, mostly male (61%) and white (68%), with plasma cell (58%) and myeloid (42%) diseases participated in 149 values discussions. Initial discussions averaged 17.7 minutes; subsequent discussions were 13.3 minutes. Most patients were comfortable discussing their values and indicated it was important and helpful for them, as well as beneficial for their caregivers. Patients reported feeling heard and understood by their care team following values discussions. Clinicians were comfortable having the discussions, felt they were beneficial, and indicated learning new information about their patients beyond their diagnosis.</p><p><strong>Conclusions: </strong>Incorporating discussions of patients' HRVs into routine HSCT care was found to be feasible and acceptable in this pilot study. Feedback from patients and providers was overwhelmingly positive. Based on these results, the program has been refined and expanded to include all patients receiving HSCT and chimeric antigen receptor T cell (CAR-T) therapy, with plans to study the clinical impact of this approach.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865541","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":"Incidence, risk factors, and outcomes of BK hemorrhagic cystitis in hematopoietic stem cell transplantation from HLA-matched and haploidentical donors with post-transplant cyclophosphamide.","authors":"Pedro Chorão, Marta Villalba, Aitana Balaguer-Roselló, Juan Montoro, Pablo Granados, Carmen Gilabert, Francisca Panadero, André Airosa Pardal, Eva María González, Santiago de Cossio, Rafael Benavente, María Dolores Gómez, Inés Gómez, Pilar Solves, Marta Santiago, Pedro Asensi, Pilar Lloret, Juan Eiris, David Martínez, Alberto Louro, Paula Rebollar, Aurora Perla, Miguel Salavert, Javier de la Rubia, Miguel Á Sanz, Jaime Sanz","doi":"10.1016/j.jtct.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.006","url":null,"abstract":"<p><strong>Background: </strong>BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes.</p><p><strong>Objectives: </strong>This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis. Furthermore, we analyze risk factors for BK-HC and its impact on renal function and transplant outcomes.</p><p><strong>Study design: </strong>Retrospective analysis of BK-HC episodes in patients undergoing HSCT from 167 MSD, 129 MUD and 103 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity, and mesna was used prophylactically with PTCy.</p><p><strong>Results: </strong>The incidence of grade 2-4 BK-HC was 23%, with a higher prevalence of grades 3-4 in HAPLO (19%), compared to MSD (11%) and MUD (8%) recipients (p=0.02). BK-HC was diagnosed at a median of 29 days after HSCT and symptoms persisted for a median of 27 days, with longer duration in grade 3-4 cases (p=0.02). Additionally, higher grades were associated with a greater transfusion burden (p<0.001). JC virus coinfection was detected in 24%, and cytomegalovirus viruria in 17%, which was not treated. BK antiviral treatment beyond supportive care was used in only two patients, while antibacterial treatments were prescribed in 28% for urinary symptoms and in 57% for concomitant infections in other sites. Younger age and HAPLO donors were significant risk factors for developing higher-grade BK-HC. No interaction was seen between age and conditioning intensity. Importantly, BK-HC did not significantly impact overall survival or graft-versus-host disease-free relapse-free survival as a time-dependent variable, as well as non-relapse mortality. Furthermore, BK-HC patients maintained stable creatinine renal clearance at 1 year post-transplant.</p><p><strong>Conclusions: </strong>BK-HC is a relatively early frequent complication in allogeneic HSCT with PTCy, especially in HAPLO recipients, with symptoms typically lasting a median of three weeks. Supportive care remains the mainstay of treatment, while specific antiviral treatments are rarely needed. The role of cidofovir and concomitant CMV viruria treatment are yet to be established. Our findings suggest that BK-HC does not significantly impact transplant outcomes and renal function.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of early WT1 mRNA reduction after remission induction in newly diagnosed acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation.","authors":"Takafumi Tsushima, Chiharu Kimeda, Natsumi Yoda, Kosuke Matsuo, Kazusuke Tanaka, Yasuhito Hatanaka, Rena Matsumoto, Sonoko Shimoji, Yoshikazu Utsu, Shin-Ichi Masuda, Nobuyuki Aotsuka","doi":"10.1016/j.jtct.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.007","url":null,"abstract":"<p><strong>Background: </strong>Wilms' Tumor (WT1) mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of WT1 mRNA after initial remission induction of patients with AML who have received transplant treatments.</p><p><strong>Objective: </strong>Thus, we retrospectively analyzed the clinical features and prognostic impact of WT1 mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in WT1 mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction.</p><p><strong>Study design: </strong>This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had WT1 mRNA quantified.</p><p><strong>Results: </strong>Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in WT1 mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in WT1 mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS.</p><p><strong>Conclusion: </strong>We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in WT1 mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of WT1 mRNA reduction after initial remission induction.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Analysis of Fresh versus Cryopreserved Allogenic Bone Marrow Transplant within a Pediatric Population: A Change in Practice Due to the COVID-19 Pandemic.","authors":"Rhea Hans, Charlotte Schwalbach, Roberta H Adams, Holly Miller, Dana Salzberg, Mohamad Sinno, Kristen Beebe, Daniela Giralt, Jennifer Stahlecker, Jeff Crosby, Jefferson Lin, Lucia Mirea, Kevin Land, Alexander Ngwube","doi":"10.1016/j.jtct.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.004","url":null,"abstract":"<p><strong>Background: </strong>Several adult studies show mixed reports in clinical outcomes between cryopreserved and fresh stem cell products, with majority reporting no significant differences and others report that there are differences in outcomes. There is limited literature reporting its impact on outcomes in pediatric hematopoietic cell transplantation (HSCT).</p><p><strong>Objective: </strong>To compare clinical outcomes between fresh vs cryopreserved stem cell treatment in pediatric HSCT.</p><p><strong>Study design: </strong>A retrospective chart review was conducted on allogenic HSCT at Phoenix Children's Hospital between January 1, 2016, and March 31, 2023. The study included 181 patients, with 105 receiving fresh stem cell products and 76 receiving cryopreserved products. Clinical outcomes including, neutrophil and platelet recovery, graft versus host disease, immune reconstitution and survival outcome were compared.</p><p><strong>Results: </strong>Study subjects had median follow-up of 997 (range 12-2642) days. 92 patients were treated for a malignant disease (leukemia/lymphoma) and 89 were treated for a non-malignant disease (hemoglobinopathies, immunodeficiency/immune dysregulation, and bone marrow failure). 124 stem cell products were from bone marrow and 57 were from peripheral blood. Comparisons between fresh vs cryopreserved treatments found no significant difference in days to neutrophil engraftment (p=0.47) or platelet engraftment (p=0.94). No difference in the incidence of acute graft versus host disease or chronic graft versus host disease (p = 0.70) between both groups. Immune reconstitution at 365 days post-transplant did not vary significantly between treatment groups for CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56/16+ NK cells. Overall survival at 2 years was similar in the fresh vs cryopreserved (86.7% vs 84.2%; p = 0.64).</p><p><strong>Conclusion: </strong>These observations suggest that cryopreserved stem cell product is a reasonable alternative with comparable efficacy and potentially offering logistical advantages. Further research with larger pediatric cohorts is recommended to confirm non-inferiority of cryopreserved treatments in pediatric HSCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839445","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":"Chronic graft-versus-host disease adversely impacts school performance in children and young adults.","authors":"Zahra Hudda, Amanda Flannery, Patricia Dillhoff, Kristen Webster, Jodi Jacobs, Sarah Strong, Jennifer Detzel, Stella M Davies, Pooja Khandelwal","doi":"10.1016/j.jtct.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.005","url":null,"abstract":"<p><strong>Background: </strong>Chronic graft-versus-host disease (cGVHD) adversely impacts return to work for adult allogeneic hematopoietic stem cell transplant (HSCT) survivors, but no data exist on children with cGVHD transitioning back to school. We hypothesized that cGVHD adversely impacts broad aspects of school experience of children compared to their allogeneic-HSCT peers without cGVHD.</p><p><strong>Methods: </strong>We conducted a single center cross-sectional pilot study using a 42-item questionnaire, investigating academic performance and social-emotional aspects of schooling pre-and post-HSCT. Forty allogeneic-HSCT patients of school-age completed the questionnaire, and responses were compared between patients with and without cGVHD.</p><p><strong>Results: </strong>Twenty patients had cGVHD while 20 age or gender matched allogeneic-HSCT patients without cGVHD were controls. Ten of the 20 cGVHD patients experienced academic delays, of whom 2 were unable to resume or commence school due to cGVHD. All controls resumed/commenced school post-HSCT. Patients with cGVHD were chronically absent, as 8 of the 18 cGVHD patients missed ≥4 days of school per month post-HSCT compared to 0/20 controls (p≤0.001). Profound barriers to school participation specific to cGVHD were appreciated with an average of 3 concurrent barriers (range 1-7) ranging from physical appearance to clothing discomfort. Significant gaps in school services were identified as only 6 (33%) cGVHD had school accommodations post-HSCT.</p><p><strong>Conclusions: </strong>Academic challenges and emotional and psychosocial impacts are profound. Future studies evaluating the feasibility of standardizing early school-based interventions are required.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829512","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":"Allogeneic Hematopoietic Cell Transplantation in Elderly Patients in a Latin American Country: Analysis of 11 Years of Data from the Brazilian Registry SBTMO/CIBMTR.","authors":"Fernando Barroso Duarte, Yhasmine Delles Oliveira Garcia, Nelson Hamerschlak, Vaneuza Araújo Moreira Funke, Maria Claudia Rodrigues Moreira, Alessandra Aparecida Paz, Jayr Schmidt Filho, Claudia Caceres Astigarraga, Roberto Luiz da Silva, Vinícius Campos de Molla, Alexandre Silvério, Vanderson Geraldo Rocha, João Victor Piccolo Feliciano, George Maurício Navarro Barros, Vergílio Antônio Rensi Colturato, Samir Kanaan Nabhan, João Samuel de Holanda Farias, Ana Carolina Arrais Maia, Ângelo Atalla, Ricardo Chiattone, Maria Cristina Martins de Almeida Macedo, Milton Alexandre Ferreira Aranha, Yana Augusta Novis Zogbi, Décio Lener, Rodolfo Daniel de Almeida Soares, Phillip Scheinberg, Rodolfo Froes Calixto, Gustavo Machado Teixeira, Marcos Paulo Colella, Celso Arrais Rodrigues, Anderson João Simione, Cinthya Corrêa da Silva, Paul J Martin, Mary E Flowers","doi":"10.1016/j.jtct.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.003","url":null,"abstract":"<p><p>This study analyzed recent changes in the utilization of allogeneic HCT for treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative diseases (MPD) and the survival of HCT recipients ≥60 years of age in Brazil. This retrospective registry study included patients who received a first allogeneic HCT from any donor between 2012 and 2023. Of the 6657 patients, 444 (7%) were 60 years of age or older who received grafts from HLA-matched related (42%) or unrelated (20%) donors or HLA-haploidentical donors (32%). The proportion of HCT recipients 60 years of age or older increased gradually from 3.2% in 2012 to 16% in 2023 mostly due to the increased use of HLA-haploidentical donors since 2018. Overall survival (OS) at day 100 was 77%, and estimated OS at 12 months was 53% (95% CI, 48-58). OS at 12-months was higher for transplants during 2015-2017 (58%) and 2018-2020 (68%) compared to 2012-2014 (45%), but it did not differ for those during 2021-2023 (49%). Mortality with HLA-haploidentical donors (HR 2.35; 95%CI; 1.65-3.34 [p <0.001]) and cord blood donors (HR 4.68; 95%CI,1.29-16.9 [p= 0.01]) was higher than with HLA-matched related donors. Mortality was lower for transplants during the 2015-2020 period (HR 0.57; 95%CI, 0.34-0.96 [0.037]) than for those during 2012-2014.This study revealed a gradual increase in the use of allogeneic HCT in individuals aged 60 years and older in Brazil. While use of haploidentical donor has increased worldwide, its association with increased mortality in elderly population deserves caution.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824438","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":"Neurotoxicity and Rare Adverse Events in BCMA-Directed CAR T Cell Therapy: A Comprehensive Analysis of Real-World FAERS Data.","authors":"Moataz Ellithi, Magdi Elsallab, Matthew A Lunning, Sarah A Holstein, Smriti Sharma, Jonathan Q Trinh, Jihyun Ma, Marcela V Maus, Matthew J Frigault, Christopher R D'Angelo","doi":"10.1016/j.jtct.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.12.002","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T (CAR T) cell therapies have emerged as a valuable treatment modality for patients with plasma cell disorders. As the population of patients receiving CAR T therapies grows, identification and management of associated rare toxicities have become increasingly crucial.</p><p><strong>Objective: </strong>To identify safety signals associated with commercial anti-B-cell maturation antigen (BCMA) CAR T therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Study design: </strong>This is a cross-sectional analysis of the adverse events (AE) reports associated with ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), submitted to FAERS between January 2021 and December 2023. AE frequencies were summarized using descriptive statistics, and safety signals were explored by measuring the reporting odds ratio (ROR) compared to control groups.</p><p><strong>Results: </strong>Among 4,472,782 unique FAERS reports, 1,496 involved BCMA-directed CAR-T therapies. AEs reported more frequently included immune associated conditions and neurological disorders. Neurotoxicity associated with cilta-cel predominantly manifested as cranial nerve palsies, parkinsonism, acute and chronic polyneuropathies, while ide-cel neurotoxicity presented as confusion, disorientation, seizures, balance disturbances, and tremors. In cilta-cel reports, other safety signals included Guillain-Barre syndrome (ROR: 17.1, 95% CI 6.1 -47.5), intracranial hemorrhage and cerebrovascular accidents (ROR: 2.9, 95% CI 1.8 -4.8), haemophilus infections (ROR: 34.2, 95% CI 11.8-98.9) and cytomegalovirus infections (ROR: 3.9, 95% CI 1.6 -9.5). For ide-cel, new signals included parkinsonism (ROR: 13.7, 95% CI 5.5-34.5), acute and chronic sarcoidosis (ROR: 197.1, 95% CI 32.9 -1180.1), ventricular arrhythmias, and cardiac arrest (ROR: 3.9, 95% CI 2.1-7.3).</p><p><strong>Conclusion: </strong>This data provides a comprehensive insight into the safety profiles of the commercial BCMA-directed CAR T therapies, underscoring the importance of vigilant post-marketing surveillance to mitigate potential risks.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822711","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}