Transplantation and Cellular Therapy最新文献

{"title":"Antibiotic Prophylaxis During Allogeneic Stem Cell transplantation-A Comprehensive Single Center Retrospective Analysis.","authors":"Charlotte K F Neuerburg, Friederike Schmitz, Marie-Therese Schmitz, Susanne Rehnelt, Martin Schumacher, Marjio Parčina, Matthias Schmid, Dominik Wolf, Peter Brossart, Tobias A W Holderried","doi":"10.1016/j.jtct.2024.09.011","DOIUrl":"10.1016/j.jtct.2024.09.011","url":null,"abstract":"<p><strong>Background: </strong>Prophylactic antibiotics are still controversial during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our transplant center, we suspended antibiotic prophylaxis during allo-HSCT in 2017.</p><p><strong>Objective: </strong>The main objective of this study was the detailed analysis of the potentially beneficial impact of omittance of standard antibiotic prophylaxis during allo-HSCT in survival and Graft-versus-Host disease (GvHD) development, especially with consideration of confounding factors and competing events. Secondary objectives were the evaluation of the risk of severe infections and transplant-related mortality without antibiotic prophylaxis, the detailed assessment of bacterial and viral infections including multiresistant pathogens as well as occurrence of relapse in both groups. This study aims to support the development of future antibiotic strategies in allo-HSCT.</p><p><strong>Study design: </strong>We retrospectively analyzed patient outcome in the time periods before (between December 2012 and February 2017) and after suspension (between March 2017 and June 2020) of antibiotic prophylaxis during allo-HSCT. Relevant clinical outcome parameters of the patients (n = 221) were collected by chart-review in the two groups (with antibiotic prophylaxis n = 101 versus without antibiotic prophylaxis n = 120). All patients were 18 years or older. Propensity score methods were used to adjust for potentially confounding patient characteristics. To address competing events, transitions between moderate/severe acute and chronic GvHD, relapse and death were analyzed using an inverse-propensity score weighted multistate modeling approach.</p><p><strong>Results: </strong>While we observed a trend towards an improved outcome in the cohort without antibiotic prophylaxis, the inverse-propensity-score-weighted analyses did not show significant differences between the two groups in overall survival (OS) (P = .811) or development of acute GvHD (aGvHD) grade 3/4 (P = .158) and chronic moderate/severe GvHD (cGvHD) (P = .686). Multistate analysis respecting competing events revealed comparable estimated probabilities without antibiotic prophylaxis versus with antibiotic prophylaxis in OS (35.0% [95% CI: 28.2%-42.7%] versus 35.3% [95% CI: 27.8%-41.1%]) as well as development of aGvHD grade 3/4 (7.7% [95% CI: 5.9%-12.2%] vs. 10.6% [95% CI: 7.7%-15.7%]) and moderate/severe cGvHD (21.0% [95% CI: 17.7%-30.0%] vs. 23.8% [95% CI: 19.6%-31.4%]). Similar analyses showed also no significant differences in relapse rate, transplant-related mortality, relapse-related mortality, or GvHD-free/relapse-free survival between the two groups. An observed increase in severe infections without antibiotic prophylaxis did not lead to a significantly higher mortality rate. Viral reactivation and detection of multiresistant bacteria were comparable, yet a higher incidence of Clostridioides difficile infections was observed in patie","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296370","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":"Risk-Based Qualification of Cellular Starting Material Collection Sites: Tools to Determine Scope of Manufacturer Audits and Reduce Duplicative Efforts.","authors":"Peter Holman, Kara Wacker, Linda Barnes, Joan Myers, Tracey Hlucky, Victoria Walters, Christina Anderson, William Shingler, Karishma Contractor","doi":"10.1016/j.jtct.2024.09.006","DOIUrl":"10.1016/j.jtct.2024.09.006","url":null,"abstract":"<p><p>Cellular and Gene Therapy product (CGT product) manufacturers are required by regulations to qualify sites performing cell collection and processing as part of their manufacturing processes. The use of audits to qualify a site is part of the traditional supplier quality models for drug products. Due to the rapid growth of the CGT industry in recent years, healthcare institutions and manufacturers are finding it difficult to manage the increasing workload and resources needed to support audits when they are applied to the provision of Cellular Starting Material (CSM) collection from patients/subjects for the purpose of manufacturing. To alleviate this audit burden, several manufacturers have applied risk-based approaches to determine the needs and scope of audits. The authors of this commentary recommend that all manufacturers utilize a risk-based assessment program when appropriate and explain the use of tools created to facilitate a risk-based approach to streamline and reduce duplicative audits. This approach and tools, created by The NextGen Industry Working Group (IWG) site certification workstream with representation from pharmaceutical and biotech companies, health care institutions, accrediting organizations, and other stakeholders, is aligned with proposals from other multistakeholder groups, including the ASTCT 80/20 Task Force. The tools aim to streamline the site qualification processes performed by each manufacturer, offering a standardized approach to audits or gap analysis assessments. Offering an abbreviated audit model for sites that have already attained accreditation through agencies such as the AABB (Association for the Advancement of Blood & Biotherapies) and FACT (Foundation for the Accreditation of Cellular Therapy), helping the manufacturer to focus on product-specific requirements rather than re-evaluating systems that have already been audited in great detail by other parties.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296359","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":"Proceedings of the 2024 Third Annual ASTCT-NMDP ACCESS Initiative Workshop.","authors":"Jeffery J Auletta, Jennifer Holter-Chakrabarty, Pashna Munshi, Sarah Wall, Nandita Khera, Jess Knutson, Alexandra Gomez-Arteaga, Anurekha G Hall, Jackie Foster, Amber Ruffin, Delilah Robb, Eneida Nemecek, Rayne Rouce, Stella M Davies","doi":"10.1016/j.jtct.2024.09.004","DOIUrl":"10.1016/j.jtct.2024.09.004","url":null,"abstract":"<p><p>The Third Annual Workshop of the American Society for Transplantation and Cellular Therapy (ASTCT) and National Marrow Donor Program (NMDP) ACCESS Initiative occurred on July 23 and 24, 2024. Content from the workshop is provided to inform the hematopoietic cell transplantation (HCT) and cellular therapy (CT) ecosystem about progress and direction of the collaborative. Highlights from the meeting are reviewed, including the inaugural Corporate Roundtable and Advocacy Day, new partnerships with non-profit organizations, and updates on projects from the Awareness, Poverty and Race and Ethnicity Inequity Committees. In addition, the Junior Faculty and Trainee Immersion Program-sponsored efforts in workforce diversity and physician advocacy are presented. Lastly, continued education was provided on patient and caregiver participation as well as community engagement. As it enters its third year, the ASTCT-NMDP ACCESS Initiative will transition from foundation building as a grass roots collaborative to intentional impact in reducing barriers and improving outcome disparities for all patients in need of HCT/CT. Enthusiasm for and participation in the ACCESS Initiative remain high. Both are needed to sustain progress in achieving its goal in enabling all patients in need to receive HCT/CT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296375","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 Letermovir for Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant.","authors":"Ibrahim N Muhsen, Kristen E Shaver, Tao Wang, Mengfen Wu, Premal Lulla, Carlos A Ramos, Rammurti T Kamble, Helen E Heslop, George Carrum, LaQuisa C Hill","doi":"10.1016/j.jtct.2024.09.009","DOIUrl":"10.1016/j.jtct.2024.09.009","url":null,"abstract":"<p><p>In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy or CMV disease) within 100 days post-transplant. Secondary outcomes included the cumulative incidence of acute GvHD (grade ≥ 2), the cumulative incidence of extensive chronic GvHD, and overall survival. A total of 84 alemtuzumab TCD URD allo-HSCT recipients were included in the analysis, 30 of whom received letermovir (letermovir group) and 54 who did not receive letermovir (control group). The median age was 59 years (range: 26-75 years) and 55.5 years (range: 20-73 years) in the letermovir and control group, respectively. Most recipients (66.7%) in both groups received unrelated matched allografts, and myeloid neoplasms were the most common indication for allo-HSCT. A significantly lower cumulative incidence of significant CMV infection within 100 days was seen in the letermovir group compared to the control group (10.0% [95% CI: 2.5-23.9%] versus 55.6% [95% CI: 41.2-67.8%], P < .0001). There was no statistically significant difference in the incidence of acute GvHD (grade ≥ 2) or overall survival between the 2 groups. However, lower rates of extensive chronic GvHD were noted in the letermovir group (10.5% [95% CI: 2.6-24.9%] versus. 36.5% [95% CI: 23.6-49.5%], P = .0126). These results demonstrate the efficacy of letermovir in decreasing the rates of clinically significant CMV infection in patients undergoing alemtuzumab T-cell depleted allo-HSCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296373","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":"Racial and Ethnic Disparities in Autologous Hematopoietic Cell Transplantation Utilization in Multiple Myeloma Have Persisted Over Time Even After Referral to a Transplant Center.","authors":"James Fan Wu, Noel Estrada-Merly, Binod Dhakal, Meera Mohan, Ravi Kishore Narra, Marcelo C Pasquini, Anita D'Souza","doi":"10.1016/j.jtct.2024.09.010","DOIUrl":"10.1016/j.jtct.2024.09.010","url":null,"abstract":"<p><p>Despite the use of autologous hematopoietic cell transplantation (AHCT) in treatment of multiple myeloma (MM) for almost 40 years and its persistence as standard of care in transplantation-eligible patients with MM even after the advent of novel agents, AHCT remains underutilized, especially in racial and ethnic minority populations. As part of a multipronged effort to quantify disparities in AHCT utilization in MM by race and ethnicity and over time in our own cancer center, we conducted an institutional review of all new patients seen at an academic transplant center for consultation for MM between 2012 and 2022, to calculate AHCT utilization and investigate the factors associated with AHCT utilization. Race and ethnicity were self-reported. Baseline characteristics were analyzed in 3 groups: non-Hispanic White (NHW), non-Hispanic Black (NHB), and Others. Reasons for not undergoing AHCT in the EHR were recorded. Multivariate analyses evaluated the effect of group on AHCT utilization, controlling for covariates related to patients not undergoing AHCT by overall cohort and consult period. Of the 1266 patients, 13.4% were NHB. The median age at consult was 66 (IQR, 23-97) years overall, 66 (IQR, 23-97) years for NHWs, 63 (IQR, 25-85) years for NHBs, and 59.5 (IQR, 31-79) years for Others (P < .01). AHCT utilization was 76% overall, 64.7% in NHBs, 76.8% in Others, and 77.8% in NHWs (P < .01). Age, cytogenetics, stage, comorbidities, and time from diagnosis to consult were associated with receipt of AHCT. From 2012-2017 to 2018-2022, NHB AHCT utilization increased from 57.5% to 69.8% (P = .10). For those who did not receive AHCT, patient preference, older age, comorbidity, early mortality, and lack of caregiver support were the most frequently documented reasons. The NHW group had greater AHCT utilization compared to the NHB group (odds ratio [OR], 3.32; 95% confidence interval [CI], 2.17-5.08; P < .0001). Absent cardiac (OR, 1.88; 95% CI, 1.35-2.62; P = .0002) or renal comorbidity (OR, 3.23; 95% CI, 2.03-5.15; P < .0001) was associated with receipt of AHCT. Older age at consult (OR, .89; 95% CI, .87-.90; P < .0001) and longer time from diagnosis to consult (OR, .97; 95% CI, .95-.98; P < .0001) were associated with lower AHCT utilization. While AHCT utilization increased from 2012-2017 to 2018-2022 in NHBs compared to NHWs, it remained significantly lower. Racial and ethnic AHCT underutilization has improved over time, but disparities persist. Younger age at consult, shorter time from diagnosis to consult, and lack of cardiac and renal comorbidities also are associated with AHCT utilization.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296357","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":"Levels of C-reactive protein and body temperature elevation during neutropenia predict engraftment and non-relapse mortality for unrelated single-unit cord blood transplantation in adults.","authors":"Takaaki Konuma,Maki Monna-Oiwa,Seiko Kato,Shohei Andoh,Masamichi Isobe,Yasuhito Nannya,Satoshi Takahashi","doi":"10.1016/j.jtct.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.09.008","url":null,"abstract":"BACKGROUNDCord blood transplantation (CBT) presents unique challenges related to inflammation during neutropenia, such as mucosal damage, infections, and the potential development of pre-engraftment syndrome or pre-engraftment immune reaction. These factors can contribute to significant inflammation and infection shortly after CBT. However, the effect of severe inflammation during neutropenia, specifically elevated C-reactive protein (CRP) level and body temperature, on post-transplant outcomes after CBT remains unclear.OBJECTIVEThis retrospective study aimed to investigate the association between maximum CRP level, maximum body temperature during neutropenia, and post-transplantation outcomes in adult patients undergoing single-unit CBT.STUDY DESIGNWe retrospectively evaluated the impact of maximum CRP level and maximum body temperature during neutropenia on post-transplantation outcomes in adults who underwent single-unit unrelated CBT between 1998 and 2023 at our institution.RESULTSA total of 336 adult patients were included in this study. The median maximum CRP level before neutrophil recovery was 7.75 mg/dL (interquartile range [IQR], 4.70 to 12.05 mg/dL) at a median of 14 days (IQR, 8 to 16 days). The median maximum body temperature before neutrophil recovery was 39.5°C (IQR, 39.0 to 40.0°C) at a median of 15 days (IQR, 12 to 17 days). In the multivariate analysis, a maximum CRP level≥20 mg/dL was significantly associated with lower neutrophil recovery (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.23 to 0.59; P<0.001), lower platelet recovery (HR, 0.28; 95% CI, 0.16 to 0.48; P<0.001), and a higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (HR, 16.42; 95% CI, 4.11 to 65.54; P<0.001), which resulted in higher non-relapse mortality (NRM) (HR, 5.16; 95% CI, 2.62 to 10.15; P<0.001) and worse overall survival (HR, 2.81; 95% CI, 1.66 to 4.78; P<0.001). Similarly, a maximum body temperature≥40.5°C was significantly associated with lower neutrophil recovery (HR, 0.51; 95% CI, 0.33 to 0.79; P=0.002), lower platelet recovery (HR, 0.55; 95% CI, 0.38 to 0.79; P=0.001), higher incidence of grades III to IV acute GVHD (HR, 2.93; 95% CI, 1.24 to 6.88; P=0.013), and extensive chronic GVHD (HR, 2.47; 95% CI, 1.22 to 4.97; P=0.011), which resulted in higher NRM (HR, 3.43; 95% CI, 1.53 to 7.67; P=0.002).CONCLUSIONMaximum CRP level and maximum body temperature during neutropenia were significantly associated with lower hematopoietic recovery and higher NRM following single-unit CBT in adults. Further studies are warranted to explore early intervention strategies aimed at preventing severe inflammation and improving post-transplant outcomes in single-unit CBT.","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269338","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,Rakhee Vaidya,Ferdous Ahmed,Hamid Ehsan,Tamara K Moyo,Ryan W Jacobs,Yifan Pang,Steven Park,Michelle Wallander,Vishal Shroff,Victoria Boseman,Travis Beam,Jennifer Elder,Melissa Yountz,Rebecca D Jennings,Dianna S Howard,Belinda Avalos,Edward A Copelan,Ruben Mesa,Nilanjan Ghosh","doi":"10.1016/j.jtct.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.09.007","url":null,"abstract":"BACKGROUNDThe implementation of 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).OBJECTIVEHerein, 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 DLBCL who received CAR T therapy.STUDY DESIGNWe conducted a retrospective study of adult patients with R/R 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.RESULTSThe 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 vs. 9 days, p < .001). Of those with private insurance (n=63), 35% needed a single case agreement (SCA) which led to significant delay in receiving financial clearance (median 50.5 vs.19 days, p < .001) and increased decision-to-vein time (median 75 vs. 55 days, p < .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, n = 9) and non-conforming products being the longest (median 94.5 days, n = 6) (p< .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 vs. 21.0 months, p < .001).CONCLUSIONDecision-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 hurdles, such as SCAs and insurance approvals, for timely access to CAR T therapy for patients with DLBCL.","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","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}

{"title":"ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies.","authors":"Piyanuch Kongtim,Pongthep Vittayawacharin,Jun Zou,Samer Srour,Brian Shaffer,Roman M Shapiro,Ankur Varma,Joseph McGuirk,Bhagirathbhai R Dholaria,Shannon R McCurdy,Amy E DeZern,Nelli Bejanyan,Asad Bashey,Sabine Furst,Luca Castagna,Jacopo Mariotti,Annalisa Ruggeri,Rebeca Bailen,Takanori Teshima,Huang Xiao-Jun,Carmen Bonfim,Fleur Aung,Kai Cao,Paul A Carpenter,Mehdi Hamadani,Medhat Askar,Marcelo Fernandez-Vina,Alin Girnita,Stefan O Ciurea","doi":"10.1016/j.jtct.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.09.005","url":null,"abstract":"Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204642","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, Franco Castillo Tokumori, Zhengming Chen, Marie Liu, Sebastian A Mayer, Ghaith Abu Zeinah, Tsiporah B Shore, Ellen K Ritchie, Richard T Silver, Joseph M Scandura, Gail J Roboz, Koen van Besien, Alexandra Gomez-Arteaga","doi":"10.1016/j.jtct.2024.08.023","DOIUrl":"10.1016/j.jtct.2024.08.023","url":null,"abstract":"<p><p>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 (P = .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 (P = .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%, P = .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) (P = .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 (P = .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.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-05","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":"Preadmission Penicillin Allergy Evaluation Before Hematopoietic Stem Cell Transplantation Optimizes Febrile Neutropenia Treatment and Inpatient Resource Utilization.","authors":"George X Huang, Lauren E Merz, Geneva D Mehta, Kathleen D Marquis, Kylie Besz, Donna-Marie Lynch, Corey Cutler, Mariana C Castells","doi":"10.1016/j.jtct.2024.08.021","DOIUrl":"10.1016/j.jtct.2024.08.021","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Febrile neutropenia is a common complication of conditioning chemotherapy for hematopoietic stem cell transplant (HSCT), but a major barrier for optimal treatment of febrile neutropenia is historical penicillin allergies. Our group recently published a development of a clinical pipeline for delabeling penicillin allergies in adult patients planned to undergo hematopoietic stem cell transplant (HSCT). In this retrospective cohort study, we followed patients to evaluate their outcomes during inpatient admission for HSCT. We hypothesized that, among patients planned for HSCT with a self-reported penicillin allergy, completing penicillin allergy testing (amoxicillin ingestion challenge with or without concomitant penicillin skin testing) prior to HSCT admission would be associated with differences in inpatient treatment for febrile neutropenia (including antibiotic selection and timing of antibiotic administration) and improved inpatient resource utilization (including nursing and inpatient physician consults). We identified patients with a self-reported penicillin allergy who answered a penicillin allergy questionnaire and were subsequently admitted to our institution for HSCT. We divided the cohort into 2 groups: patients whose penicillin allergy was evaluated prior to admission (EPTA) and patients whose penicillin allergy was not evaluated prior to admission (NEPTA). We then performed comparison between the 2 groups for general clinical outcomes of HSCT admission (duration of admission, need for ICU transfer, readmission rate, etc.), febrile neutropenia treatment, and inpatient resource utilization. Statistics were calculated using the nonparametric 2-tailed Fisher exact test for categorical outcomes and the nonparametric 2-tailed Mann-Whitney U test for numerical outcomes. Within our cohort, 35 patients completed penicillin allergy testing prior to HSCT admission (EPTA) and 44 patients did not (NEPTA). Demographics were similar between these groups, and there was no significant difference in the rate of febrile neutropenia during HSCT admission (EPTA 64% versus NEPTA 66%, P = 1.00). EPTA patients were significantly more likely to receive standard first-line antibiotics (cefepime or ceftazidime) for febrile neutropenia (EPTA 95% versus NEPTA 65%, P = .015) and time between febrile neutropenia onset and antibiotic administration was shorter (EPTA mean 66 mins versus NEPTA mean 121 mins, P = .0058). No patients in the EPTA group experienced an immediate hypersensitivity reaction (hives, anaphylaxis, etc.) or severe cutaneous adverse reaction (SCAR) during HSCT admission. EPTA patients were also significantly less likely to require 1:1 nursing for antibiotic test doses, challenges, and desensitizations (EPTA 0% versus NEPTA 49%, P &lt; .0001); less likely to require inpatient allergy consult (EPTA 0% versus NEPTA 12%, P = .031); and less likely to require inpatient antimicrobial stewardship consult (EPTA 0% versus NEPTA 13%, P = .013) during their","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146323","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}