Transplantation and Cellular Therapy最新文献

{"title":"Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Transfusion-Dependent Thalassemia: A Systematic Review and Meta-Analysis","authors":"Hongwen Xiao ,&nbsp;Qiulin Huang ,&nbsp;Yongrong Lai ,&nbsp;Rongrong Liu","doi":"10.1016/j.jtct.2024.12.001","DOIUrl":"10.1016/j.jtct.2024.12.001","url":null,"abstract":"<div><div>Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) presents a promising therapeutic option for pediatric transfusion-dependent thalassemia, particularly in the scarcity of matched donors. Despite its potential, the comprehensive evaluation of this method through large-scale prospective studies remains lacking. This study aims to systematically summarize the efficacy and safety of haplo-HSCT in thalassemia, thereby providing further evidence-based insights for clinical practice. A comprehensive literature search was conducted across PubMed, Embase, and Web of Science databases through June 2024 to ensure a robust analysis of the available evidence. Data extraction was independently performed by 2 reviewers. The analysis utilized the inverse variance method with a 95% confidence interval (95% CI) to calculate the pooled proportion. To assess the heterogeneity among the studies, Cochran's Q test and Higgins' I-squared statistical methods were utilized. A random-effects model was employed to accommodate the variability between study results. Furthermore, subgroup analyses were explored differences in outcomes based on conditioning regimens and graft versus host disease (GVHD) prophylaxis. Conditioning regimens were categorized into reduced-intensity conditioning and myeloablative conditioning regimens. GVHD prophylaxis was classified into post-transplantation cyclophosphamide and non-post-transplantation cyclophosphamide. In this meta-analysis, we reviewed data from 10 studies encompassing 356 patients with thalassemia who underwent haplo-HSCT. Out of these, 328 patients survived until the follow-up date, resulting in a pooled overall survival rate of 92.4% (95% CI, 86.9-96.7; I² = 54.32%). The thalassemia-free survival was 84.5% (95% CI, 75.3-91.9; I² = 77.64%), and the graft failure rate was 8.1% (95% CI, 2.5-16.4; I² = 81.78%). The transplantation-related mortality stood at 7.4% (95% CI, 3.6-12.5; I² = 55.74%), with infections noted as the primary cause of death. The pooled proportion of acute graft versus host disease (aGVHD), grade 2-4 aGVHD, and grade 3-4 aGVHD were 29.6% (95% CI, 16.7-42.5, <em>I²</em> = 92.48%), 22.3% (95% CI, 10.1-42.1, <em>I²</em> = 80.06%), and 9.1% (95% CI, 2.8-17.7, <em>I²</em> = 67.92%), respectively. Subgroup analyses revealed no significant differences in these outcomes when comparing myeloablative conditioning to reduced-intensity conditioning, or post-transplantation cyclophosphamide to non-post-transplantation cyclophosphamide prophylaxis. However, variations in sample size, patient's age and geographic region among the studies suggest these factors as potential sources of heterogeneity.</div><div>Haploidentical hematopoietic stem cell transplantation utilizes donors who are partially HLA-matched, typically family members, making it a viable option for transfusion-dependent thalassemia when fully matched donors are not available.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 101.e1-101.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795223","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":"Venous Thromboembolism Incidence and Risk Factors in Patients Undergoing Hematopoietic Stem Cell Transplantation","authors":"Miranda Benfield ,&nbsp;Jiaxian He ,&nbsp;Justin Arnall ,&nbsp;Whitney Kaizen ,&nbsp;Elizabeth Jandrisevits ,&nbsp;Karine Eboli-Lopes ,&nbsp;Brandy Dodd ,&nbsp;Michael R. Grunwald ,&nbsp;Belinda Avalos ,&nbsp;Edward Copelan ,&nbsp;Jai N. Patel","doi":"10.1016/j.jtct.2024.10.016","DOIUrl":"10.1016/j.jtct.2024.10.016","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Malignancy is a well-known risk factor for venous thromboembolism (VTE), and the Khorana risk score is effective for screening patients with solid tumors. However, there is a lack of validated screening tools and established risk factors for patients undergoing hematopoietic stem cell transplantation (HCT). Current literature reports a 2.5% to 8.5% incidence of VTE in HCT recipients. Anticoagulation is difficult to manage post-transplantation, given prolonged thrombocytopenia and the likelihood of bleeding. By identifying risk factors, a predictive model may be developed to prospectively test prophylaxis strategies in patients at the highest risk of a thromboembolic event (TE). This retrospective single-center study evaluated the cumulative incidence of TE at 6 months following allogeneic or autologous HCT in adult subjects undergoing transplantation between March 2014 and December 2019. The study also aimed to identify risk factors for developing a TE, evaluate the time from HCT to TE, and compare 1-year survival following HCT between patients with a TE and those without a TE. In evaluating the incidence of TE, ICD-9 and ICD-10 codes were used to determine cancer diagnosis, TE events occurring up 180 days after HCT, and comorbidities of interest. Each subject was reviewed for data accuracy by a manual retrospective chart review. Statistical tests including the cumulative incidence method with competing risks, Gray's test, and univariate and multivariate Cox proportional hazards models were used to analyze the time to first TE, evaluate risk factors, and assess 1-year survival post-HCT in relation to TEs occurring within 180 days of HCT. Variables examined included age, sex, body mass index, transplant type, hospital length of stay (LOS), history of TE prior to transplantation, active infections, graft-versus-host disease (GVHD), veno-occlusive disorder, cytomegalovirus serostatus, and other factors. The study included 636 evaluable patients; the majority were male (57.9%) and white (68.7%) and had undergone autologous HCT (68.4%). Twenty-nine patients (4.6%) experienced a TE within 180 days post-transplantation. TEs were more common in the allogeneic HCT recipients (n = 13/201; 6.5%) compared to the autologous HCT recipients (n = 16/435; 3.7%; &lt;em&gt;P&lt;/em&gt; = .122). The cumulative incidence of TE was higher in patients who developed an active infection compared to those who did not (7.6% versus 3.1%; &lt;em&gt;P&lt;/em&gt; = .011). Hospital LOS (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.0 to 1.06; &lt;em&gt;P&lt;/em&gt; = .036) and active infection (HR, 2.34; 95% CI, 1.1 to 4.95; &lt;em&gt;P&lt;/em&gt; = .027) were significantly associated with TE in univariate analysis but were not retained in the final multivariate model. There was no difference in 1-year survival between all patients who experienced a TE and those who did not; however, in the autologous HCT group, 1-year survival rate was significantly lower in patients with a TE compared to those without ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 111.e1-111.e10"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590789","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 Year of Data from the Brazilian Registry SBTMO/CIBMTR","authors":"Fernando Barroso Duarte ,&nbsp;Yhasmine Delles Oliveira Garcia ,&nbsp;Nelson Hamerschlak ,&nbsp;Vaneuza Araújo Moreira Funke ,&nbsp;Maria Claudia Rodrigues Moreira ,&nbsp;Alessandra Aparecida Paz ,&nbsp;Jayr Schmidt Filho ,&nbsp;Claudia Caceres Astigarraga ,&nbsp;Roberto Luiz da Silva ,&nbsp;Vinícius Campos de Molla ,&nbsp;Alexandre Silvério ,&nbsp;Vanderson Geraldo Rocha ,&nbsp;João Victor Piccolo Feliciano ,&nbsp;George Maurício Navarro Barros ,&nbsp;Vergílio Antônio Rensi Colturato ,&nbsp;Samir Kanaan Nabhan ,&nbsp;João Samuel de Holanda Farias ,&nbsp;Ana Carolina Arrais Maia ,&nbsp;Ângelo Atalla ,&nbsp;Ricardo Chiattone ,&nbsp;Mary E. Flowers","doi":"10.1016/j.jtct.2024.12.003","DOIUrl":"10.1016/j.jtct.2024.12.003","url":null,"abstract":"<div><div>This study analyzed recent changes in the utilization of allogeneic hematopoietic cell transplantation (HCT) for treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative diseases (MPDs) 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 human leukocyte antigen (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 to 2017 (58%) and 2018 to 2020 (68%) compared with 2012 to 2014 (45%), but it did not differ for those during 2021 to 2023 (49%). Mortality with HLA-haploidentical donors (HR, 2.35; 95% CI, 1.65-3.34 [<em>P</em> &lt; .001]) and cord blood donors (HR, 4.68; 95%,CI, 1.29-16.9 [<em>P</em> = .01]) was higher than with HLA-matched related donors. Mortality was lower for patients with transplants during the 2015 to 2020 period (HR, 0.57; 95% CI, .34-.96 [.037]) than for those during 2012 to 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 donors has increased worldwide, its association with increased mortality in the elderly population warrants caution when considering this treatment</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 79.e1-79.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","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":"Efficacy and Safety of Bispecific T-Cell Engagers in Relapsed/Refractory Multiple Myeloma: A Real-World Data-Based Case-Controlled Study","authors":"Suein Choi ,&nbsp;Ja Min Byun ,&nbsp;Sung-Soo Park ,&nbsp;Jinsun Han ,&nbsp;Sieun Oh ,&nbsp;Seungpil Jung ,&nbsp;Hyejoon Park ,&nbsp;Seunghoon Han ,&nbsp;Jung Yeon Lee ,&nbsp;Youngil Koh ,&nbsp;Young-Woo Jeon ,&nbsp;Seung-Ah Yahng ,&nbsp;Seung-Hwan Shin ,&nbsp;Sung-Soo Yoon ,&nbsp;Chang-Ki Min","doi":"10.1016/j.jtct.2024.11.010","DOIUrl":"10.1016/j.jtct.2024.11.010","url":null,"abstract":"<div><div>Although bispecific T-cell engager (BiTE) is a promising treatment for relapsed/refractory multiple myeloma (RRMM), it needs to be evaluated in a real-world setting. This study aimed to evaluate the efficacy and safety of BiTEs compared with a synthetic standard of care (SOC). From a multicenter registry database of 474 patients with RRMM who received third- or more advanced-line treatments between January 2021 and October 2023, 1:1 propensity score-matched BiTE cohort (n = 71) and SOC cohort (n = 71) were established. Matching was based on age, sex, number of prior therapies, international staging system at diagnosis, and baseline biochemical characteristics. Compared with the matched SOC cohort, the matched BiTE cohort demonstrated a significant improvement in median progression-free survival (PFS, 19.2 vs 5.4 months, hazard ratio (HR) = .50 [95% CI, .33 to .78], <em>p</em> &lt; .01). However, the overall survival (OS) was not significantly different between the two cohorts. Safety profiles showed that 37 (52%) patients in the matched BiTE cohort experienced cytokine release syndrome, mostly grade 1 (n = 29, 41%), with rare occurrences of neurotoxicity (n = 4, 5.6%). Infections were significantly more common in the matched BiTE cohort compared with the matched SOC cohort (81% vs. 49%, <em>p</em> &lt; .01). Non-B-cell mutation antigen (BCMA)-targeted BiTEs improved 6-month OS rates compared with BCMA-targeted BiTEs in monotherapy (94% [95% CI, 84 to 100] vs. 65% [95% CI, 45 to 95], <em>p</em> = .04) and combination with daratumumab (100% [95% CI, 100 to 100] vs. 77% [95% CI, 57 to 100], <em>p</em> = .20). Non-BCMA-targeted BiTEs also provided benefit for 6-month PFS rate compared with the BCMA-targeted BiTE cohort in monotherapy (76% [95% CI, 59 to 100] vs. 50% [95% CI, 31 to 82], <em>p</em> = .11) and combination with daratumumab (100% [95% CI, 100 to 100] vs. 69% [95% CI, 48 to 99], <em>p</em> = .10). Quantitative bias and sensitivity analyses confirmed the robustness of these results. This real-world data-based study underscores the potential of BiTEs to significantly enhance survival outcomes in patients with heavily treated RRMM and manageable safety profiles. The difference in clinical outcomes by BiTE targets warrants further investigation in larger clinical trials (ClinicalTrials.gov identifier: <span><span>NCT06205823</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 74.e1-74.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751799","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":"Generosity of the Unrelated Stem Cell Transplant Donor: Moving from Hope to Reality While Overcoming Challenges to Deliver the Gift of Life","authors":"Steven M. Devine","doi":"10.1016/j.jtct.2025.01.033","DOIUrl":"10.1016/j.jtct.2025.01.033","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 59-62"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080920","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":"RBC Alloimmunization in SCD: Chipping Away at the Iceberg of Implications","authors":"RCG Azbell ,&nbsp;PC Desai","doi":"10.1016/j.jtct.2025.01.035","DOIUrl":"10.1016/j.jtct.2025.01.035","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 66-68"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081019","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":"Letermovir for Prevention of Recurrent Cytomegalovirus in High-Risk Allogeneic Hematopoietic Cell Transplantation Recipients","authors":"Gyuri Han ,&nbsp;Anat Stern ,&nbsp;Yeon Joo Lee ,&nbsp;Yuxuan Li ,&nbsp;Parastoo B. Dahi ,&nbsp;Roni Tamari ,&nbsp;Boglarka Gyurkocza ,&nbsp;Ann A. Jakubowski ,&nbsp;Esperanza B. Papadopoulos ,&nbsp;Brian Shaffer ,&nbsp;Miguel-Angel Perales ,&nbsp;Karam M. Obeid ,&nbsp;Jo-Anne H. Young ,&nbsp;Genovefa A. Papanicolaou","doi":"10.1016/j.jtct.2024.12.010","DOIUrl":"10.1016/j.jtct.2024.12.010","url":null,"abstract":"<div><div>We evaluated letermovir (LTV) for secondary prophylaxis for cytomegalovirus (CMV) in allogeneic hematopoietic cell transplant recipients (HCT) at high-risk for CMV recurrence. This open-label study was 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 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 at week 14. Thirty-six patients were analyzed (CMV seropositive, n = 33; T cell-depleted HCT, n = 25; cord blood allograft, n = 5). By week 14 post-transplantation, 5 patients met the primary endpoint of cs-CMVi, for a cumulative incidence of 14.9% (95% confidence interval, 2.6% to 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, CMV-related death, or LTV-related adverse events by week 14 or by week 24. Our data support that LTV secondary prophylaxis is safe and effective in high-risk HCT recipients.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 105.e1-105.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","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":"Neurotoxicity and Rare Adverse Events in BCMA-Directed CAR T Cell Therapy: A Comprehensive Analysis of Real-World FAERS Data","authors":"Moataz Ellithi ,&nbsp;Magdi Elsallab ,&nbsp;Matthew A. Lunning ,&nbsp;Sarah A. Holstein ,&nbsp;Smriti Sharma ,&nbsp;Jonathan Q. Trinh ,&nbsp;Jihyun Ma ,&nbsp;Marcela V. Maus ,&nbsp;Matthew J. Frigault ,&nbsp;Christopher R. D'Angelo","doi":"10.1016/j.jtct.2024.12.002","DOIUrl":"10.1016/j.jtct.2024.12.002","url":null,"abstract":"<div><div>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, the identification and management of associated rare toxicities become increasingly crucial. This study aims 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). We performed 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. 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, Parkinson's disease and parkinsonism, and 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 to 47.5), intracranial hemorrhage and cerebrovascular accidents (ROR: 2.9, 95% CI 1.8 to 4.8), Haemophilus infections (ROR: 34.2, 95% CI 11.8 to 98.9) and cytomegalovirus infections (ROR: 3.9, 95% CI 1.6 to 9.5). For ide-cel, new signals included parkinsonism (ROR: 13.7, 95% CI 5.5 to 34.5), acute and chronic sarcoidosis (ROR: 197.1, 95% CI 32.9 to 1180.1), ventricular arrhythmias, and cardiac arrest (ROR: 3.9, 95% CI 2.1 to 7.3). This analysis 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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 71.e1-71.e14"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","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}

{"title":"Lipid Levels Increase to the Normal Range After Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease","authors":"Jackie Queen ,&nbsp;Emily Limerick ,&nbsp;Neal Jeffries,&nbsp;Matthew M. Hsieh,&nbsp;Robert D. Shamburek,&nbsp;Courtney D. Fitzhugh","doi":"10.1016/j.jtct.2024.12.008","DOIUrl":"10.1016/j.jtct.2024.12.008","url":null,"abstract":"<div><div>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. This retrospective cohort study characterizes lipid profiles at baseline and after nonmyeloablative allogeneic HCT for SCD. We analyzed data from 116 patients after nonmyeloablative HLA-matched sibling or haploidentical HCT for SCD at the NIH from 2009 to 2021. TC, HDL-c, LDL-c, and TG were collected pre-HCT, 1-year post-HCT, and annually thereafter. Data were analyzed using linear generalized estimating equation regression modeling. 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. 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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 82.e1-82.e8"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","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 ,&nbsp;Andrew C. Harris ,&nbsp;Lev Gorfinkel ,&nbsp;Katarzyna Ibanez ,&nbsp;Eric R. Tkaczyk ,&nbsp;Sandra A. Mitchell ,&nbsp;Stacey Albuquerque ,&nbsp;Tal Schechter ,&nbsp;Steven Pavletic ,&nbsp;Christine N. Duncan ,&nbsp;Seth J. Rotz ,&nbsp;Kirsten Williams ,&nbsp;Paul A. Carpenter ,&nbsp;Geoffrey D.E. Cuvelier","doi":"10.1016/j.jtct.2024.12.011","DOIUrl":"10.1016/j.jtct.2024.12.011","url":null,"abstract":"<div><div>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 &lt;18 yr 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 4 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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 69.e1-69.e18"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","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}