Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.013
Multiplexed gastrointestinal PCR panels (MGPPs) are frequently used to aid the diagnosis and management of diarrhea in hematopoietic stem cell transplantation (HCT) recipients. Many issues related to the optimal use of MGPPs in HCT patients remain to be clarified. We aimed to better define MGPP diagnostic and therapeutic stewardship in HCT recipients, including indications for and benefits of testing, optimal timing of tests, and interpretation of results. We retrieved 463 consecutive MGPPs ordered on 651 consecutive first HCT (312 allogeneic, 339 autologous) performed at our institution between June 2015 and June 2023. One hundred and sixteen of the 463 MGPPs (25%) identified at least 1 diarrheagenic pathogen, and 12 (3%) identified more than 1 diarrheagenic pathogen. A positive result was more likely if the test was ordered within 48 hours of a hospital admission (41%; 32 of 78) or as an outpatient (41%; 46 of 111) compared with evaluation of hospital-onset diarrhea (14%; 38 of 274). Among the positive results, the most frequent pathogens identified included Clostridioides difficile (64%), diarrheagenic Escherichia coli (20%), norovirus (9%), and adenovirus 40/41 (5%). Thirty-eight percent of the positive C. difficile MGPP determinations were associated with a positive test for toxin. In our allogeneic HCT cohort, 3% of MGPPs for hospital-onset diarrhea yielded an organism other than C. difficile. Fifty-six percent of positive and 14% of all submitted tests resulted in a change in treatment. For organisms other than C. difficile, only 1% of all tests and 5% of positive tests resulted in initiation of therapy. For patients at risk for acute graft-versus-host disease (aGVHD), a positive or negative MGPP result was not predictive of a new diagnosis of aGVHD in proximity to diarrhea onset. These results suggest that MGPP testing is most useful when performed at hospital admission or on an outpatient basis. Because MGPPs are sensitive and do not distinguish between colonization and causes of diarrhea, caution is needed when interpreting results, especially for toxin-negative C. difficile and diarrheagenic gram-negative organisms.
{"title":"Multiplexed Gastrointestinal PCR Panels for the Evaluation of Diarrhea in Hematopoietic Stem Cell Transplantation Recipients","authors":"","doi":"10.1016/j.jtct.2024.05.013","DOIUrl":"10.1016/j.jtct.2024.05.013","url":null,"abstract":"<div><p>Multiplexed gastrointestinal PCR panels (MGPPs) are frequently used to aid the diagnosis and management of diarrhea in hematopoietic stem cell transplantation (HCT) recipients. Many issues related to the optimal use of MGPPs in HCT patients remain to be clarified. We aimed to better define MGPP diagnostic and therapeutic stewardship in HCT recipients, including indications for and benefits of testing, optimal timing of tests, and interpretation of results. We retrieved 463 consecutive MGPPs ordered on 651 consecutive first HCT (312 allogeneic, 339 autologous) performed at our institution between June 2015 and June 2023. One hundred and sixteen of the 463 MGPPs (25%) identified at least 1 diarrheagenic pathogen, and 12 (3%) identified more than 1 diarrheagenic pathogen. A positive result was more likely if the test was ordered within 48 hours of a hospital admission (41%; 32 of 78) or as an outpatient (41%; 46 of 111) compared with evaluation of hospital-onset diarrhea (14%; 38 of 274). Among the positive results, the most frequent pathogens identified included <em>Clostridioides difficile</em> (64%), diarrheagenic <em>Escherichia coli</em> (20%), norovirus (9%), and adenovirus 40/41 (5%). Thirty-eight percent of the positive <em>C. difficile</em> MGPP determinations were associated with a positive test for toxin. In our allogeneic HCT cohort, 3% of MGPPs for hospital-onset diarrhea yielded an organism other than <em>C. difficile</em>. Fifty-six percent of positive and 14% of all submitted tests resulted in a change in treatment. For organisms other than <em>C. difficile</em>, only 1% of all tests and 5% of positive tests resulted in initiation of therapy. For patients at risk for acute graft-versus-host disease (aGVHD), a positive or negative MGPP result was not predictive of a new diagnosis of aGVHD in proximity to diarrhea onset. These results suggest that MGPP testing is most useful when performed at hospital admission or on an outpatient basis. Because MGPPs are sensitive and do not distinguish between colonization and causes of diarrhea, caution is needed when interpreting results, especially for toxin-negative <em>C. difficile</em> and diarrheagenic gram-negative organisms.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071102","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.017
Germline genetic testing for patients with severe aplastic anemia (SAA) is recommended to guide treatment, including the use of immunosuppressive therapy and/or adjustment of hematopoietic cell transplantation (HCT) modalities. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition often associated with cytopenias with autosomal recessive (AR) or X-linked recessive (XLR) inheritance. HLH is part of the SAA differential diagnosis, and genetic testing may identify variants in HLH genes in patients with SAA. The impact of pathogenic/likely pathogenic (P/LP) variants in HLH genes on HCT outcomes in SAA is unclear. In this study, we aimed to determine the frequency of HLH gene variants in a large cohort of patients with acquired SAA and to evaluate their association(s) with HCT outcomes. The Transplant Outcomes in Aplastic Anemia project, a collaboration between the National Cancer Institute and the Center for International Blood and Marrow Transplant Research, collected genomic and clinical data from 824 patients who underwent HCT for SAA between 1989 and 2015. We excluded 140 patients with inherited bone marrow failure syndromes and used exome sequencing data from the remaining 684 patients with acquired SAA to identify P/LP variants in 14 HLH-associated genes (11 AR, 3 XLR) curated using American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) criteria. Deleterious variants of uncertain significance (del-VUS) were defined as those not meeting the ACMG/AMP P/LP criteria but with damaging predictions in ≥3 of 5 meta-predictors (BayesDel, REVEL, CADD, MetaSVM, and/or EIGEN). The Kaplan-Meier estimator was used to calculate the probability of overall survival (OS) after HCT, and the cumulative incidence calculator was used for other HCT outcomes, accounting for relevant competing risks. There were 46 HLH variants in 49 of the 684 patients (7.2%). Seventeen variants in 19 patients (2.8%) were P/LP; 8 of these were loss-of-function variants. Among the 19 patients with P/LP HLH variants, 16 (84%) had monoallelic variants in genes with AR inheritance, and 3 had variants in XLR genes. PRF1 was the most frequently affected gene (in 8 of the 19 patients). We found no statistically significant differences in transplantation-related factors between patients with and those without P/LP HLH variants. The 5-year survival probability was 89% (95% confidence interval [CI], 72% to 99%) in patients with P/LP HLH variants and 70% (95% CI, 53% to 85%) in those with del-VUS HLH variants, compared to 66% (95% CI, 62% to 70%) in those without variants (P = .16, log-rank test). The median time to neutrophil engraftment was 16 days for patients with P/LP HLH variants and 18 days in those with del-VUS HLH variants or without variants combined (P = .01, Gray's test). No statistically significant associations between P/LP HLH variants and the risk of acute or chronic gr
背景：建议对重型再生障碍性贫血（SAA）患者进行种系遗传检测，以指导治疗，包括使用免疫抑制疗法和/或调整造血细胞移植（HCT）方式。嗜血细胞淋巴组织细胞增多症（HLH）是一种危及生命的高炎症性疾病，常伴有细胞减少症，为常染色体隐性遗传（AR）或X连锁隐性遗传（XLR）。HLH 是 SAA 鉴别诊断的一部分，基因检测可在 SAA 患者中发现 HLH 基因的变异。HLH基因中的致病/可能致病（P/LP）变异对SAA患者HCT结果的影响尚不清楚：我们旨在确定一大批获得性 SAA 患者中 HLH 基因变异的频率，并评估其与 HCT 结果的关联：再生障碍性贫血移植结果项目由美国国立癌症研究所（National Cancer Institute）和国际血液与骨髓移植研究中心（Center for International Blood and Marrow Transplant Research）合作开展，该项目包括1989年至2015年间因SAA接受HCT治疗的824名患者的基因组和临床数据。我们排除了 140 例遗传性骨髓衰竭综合征患者，并利用其余 684 例获得性 SAA 患者的外显子组测序数据，鉴定了根据 ACMG/AMP 标准策划的 14 个 HLH 相关基因（11 个 AR，3 个 XLR）中的 P/LP 变异。意义不确定的致病变异（del-VUS）被定义为不符合 ACMG/AMP P/LP 标准，但在≥3/5 个元预测因子（BayesDel、REVEL、CADD、MetaSVM 和/或 EIGEN）中有破坏性预测的变异。采用Kaplan-Meier估计器计算HCT后总生存期（OS）的概率，采用累积发病率计算器计算其他HCT结果，并考虑相关竞争风险：49名患者中有46个HLH变异体（7.2%；总数=684）。19名患者（2.8%）中的17个变异为P/LP；其中8个为功能缺失变异。在19名P/LP HLH变异患者中，16人（84%）的单拷贝变异位于AR遗传基因中，3人的变异位于XLR基因中。PRF1 是最常受影响的基因（8/19 名患者）。我们发现，有 P/LP HLH 变异和没有 P/LP HLH 变异的患者在移植相关因素方面没有明显的统计学差异。P/LP和del-VUS HLH变异患者的5年生存概率分别为89%（95% CI=72-99）和70%（95% CI=53-85%），而无变异患者的5年生存概率为66%（95% CI=62-70）（p-log-rank=0.16）。P/LP HLH变异型患者的中性粒细胞移植时间中位数为16天，而del-VUS或无变异型患者的中性粒细胞移植时间中位数为18天（p-格雷氏检验=0.01）。P/LP HLH变异与急性或慢性移植物抗宿主疾病风险之间没有统计学意义：结论：在这一庞大的获得性 SAA 患者队列中，我们发现 2.8% 的患者携带 HLH 基因中的 P/LP 变异。HLH基因变异对造血干细胞移植后的存活率没有负面影响。具有 P/LP HLH 基因变异的患者人数较少，这限制了研究提供确凿证据的能力。然而，我们的数据表明，对于携带 P/LP 变异基因的 SAA 患者，移植时无需特别考虑。
{"title":"Hemophagocytic Lymphohistiocytosis Gene Variants in Severe Aplastic Anemia and Their Impact on Hematopoietic Cell Transplantation Outcomes","authors":"","doi":"10.1016/j.jtct.2024.05.017","DOIUrl":"10.1016/j.jtct.2024.05.017","url":null,"abstract":"<div><p>Germline genetic testing for patients with severe aplastic anemia (SAA) is recommended to guide treatment, including the use of immunosuppressive therapy and/or adjustment of hematopoietic cell transplantation (HCT) modalities. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition often associated with cytopenias with autosomal recessive (AR) or X-linked recessive (XLR) inheritance. HLH is part of the SAA differential diagnosis, and genetic testing may identify variants in HLH genes in patients with SAA. The impact of pathogenic/likely pathogenic (P/LP) variants in HLH genes on HCT outcomes in SAA is unclear. In this study, we aimed to determine the frequency of HLH gene variants in a large cohort of patients with acquired SAA and to evaluate their association(s) with HCT outcomes. The Transplant Outcomes in Aplastic Anemia project, a collaboration between the National Cancer Institute and the Center for International Blood and Marrow Transplant Research, collected genomic and clinical data from 824 patients who underwent HCT for SAA between 1989 and 2015. We excluded 140 patients with inherited bone marrow failure syndromes and used exome sequencing data from the remaining 684 patients with acquired SAA to identify P/LP variants in 14 HLH-associated genes (11 AR, 3 XLR) curated using American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) criteria. Deleterious variants of uncertain significance (del-VUS) were defined as those not meeting the ACMG/AMP P/LP criteria but with damaging predictions in ≥3 of 5 meta-predictors (BayesDel, REVEL, CADD, MetaSVM, and/or EIGEN). The Kaplan-Meier estimator was used to calculate the probability of overall survival (OS) after HCT, and the cumulative incidence calculator was used for other HCT outcomes, accounting for relevant competing risks. There were 46 HLH variants in 49 of the 684 patients (7.2%). Seventeen variants in 19 patients (2.8%) were P/LP; 8 of these were loss-of-function variants. Among the 19 patients with P/LP HLH variants, 16 (84%) had monoallelic variants in genes with AR inheritance, and 3 had variants in XLR genes. <em>PRF1</em> was the most frequently affected gene (in 8 of the 19 patients). We found no statistically significant differences in transplantation-related factors between patients with and those without P/LP HLH variants. The 5-year survival probability was 89% (95% confidence interval [CI], 72% to 99%) in patients with P/LP HLH variants and 70% (95% CI, 53% to 85%) in those with del-VUS HLH variants, compared to 66% (95% CI, 62% to 70%) in those without variants (<em>P</em> = .16, log-rank test). The median time to neutrophil engraftment was 16 days for patients with P/LP HLH variants and 18 days in those with del-VUS HLH variants or without variants combined (<em>P</em> = .01, Gray's test). No statistically significant associations between P/LP HLH variants and the risk of acute or chronic gr","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176503","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.06.001
Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (P < .001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (P < .001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, P < .001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, P < .001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, P = .001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, P < .001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, P < .001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM
背景：先期自体干细胞移植（auto-SCT）仍然是符合条件的新诊断多发性骨髓瘤（NDMM）患者的标准治疗方法，尽管近来其作用受到质疑：研究旨在评估30年来接受前期自体移植的NDMM患者的特征、治疗和预后趋势：我们对1988年至2021年间在MD安德森癌症中心接受前期自体移植的NDMM患者进行了单中心回顾性分析。主要终点为无进展生存期（PFS）和总生存期（OS）。患者按接受自体移植的年份分组：1988-2000年（249人）、2001-2005年（373人）、2006-2010年（568人）、2011-2015年（815人）和2016-2021年（1036人）。荧光原位杂交法将高危细胞遗传学异常定义为del(17p)、t(4;14)、t(14;16)和1q21增益或扩增：我们分析了 3041 名 MM 患者。接受自体造血干细胞移植时的中位年龄从52岁（1988-2000年）增至62岁（2016-2021年），高危细胞遗传学的发生率也从15%增至40%（p3，从17%（1988-2000年）增至28%（2016-2021年）（p结论：尽管患者年龄和合并症负担不断增加，但这项大型真实世界研究表明，在过去30年中，接受前期自体移植的NDMM患者（包括高危疾病患者）的反应深度和生存结果均有显著改善。
{"title":"Trends in Outcomes After Upfront Autologous Transplant for Multiple Myeloma Over Three Decades","authors":"","doi":"10.1016/j.jtct.2024.06.001","DOIUrl":"10.1016/j.jtct.2024.06.001","url":null,"abstract":"<div><p>Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (<em>n =</em> 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (<em>P < .</em>001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (<em>P < .</em><span>001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, </span><em>P < .</em>001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, <em>P < .</em>001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, <em>P = .</em>001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, <em>P < .</em>001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, <em>P < .</em>001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296759","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.025
Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis that comprises 3 groups: normal (≥1 × 109/L) pre-LD ALC (LDN), low (<1 × 109/L) pre-LD ALC (LDL) + percent reduction <37.5 (%RL), and LDL ALC + percent reduction ≥37.5 (%RH). A total of 214 SOC ide-cel recipients were included in this analysis. The median patient age was 64 years (interquartile range [IQR], 57 to 69 years), median number of prior therapies was 6 (IQR, 5 to 9), and median duration of follow-up was 5.4 months (IQR, 2.1 to 8.3 months). Most patients had both low pre-A ALC (75.3%) and pre-LD ALC (77.2%), and the reduction from pre-A to pre-LD (median, .65 to .55 × 109/L) was statistically significant. Univariate analysis showed that the LDL + %RH group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LDL + %RL and LDN ALC groups (6-month PFS: 40% versus 67.6% and 60.9%; 6-month OS: 69.5% versus 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance; however, OS remained significantly worse for LDL + %RH group compared to the LDN ALC group (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.1 to 17), but the difference between the LDL + %RH versus %RL groups was not statistically significant (HR, 1.7; 95% CI, .8 to 4.0). Our findings indicate that low pre-LD ALC with high %R from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.
{"title":"Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience","authors":"","doi":"10.1016/j.jtct.2024.05.025","DOIUrl":"10.1016/j.jtct.2024.05.025","url":null,"abstract":"<div><p>Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis that comprises 3 groups: normal (≥1 × 10<sup>9</sup>/L) pre-LD ALC (LD<sub>N</sub>), low (<1 × 10<sup>9</sup>/L) pre-LD ALC (LD<sub>L</sub>) + percent reduction <37.5 (%R<sub>L</sub>), and LD<sub>L</sub> ALC + percent reduction ≥37.5 (%R<sub>H</sub>). A total of 214 SOC ide-cel recipients were included in this analysis. The median patient age was 64 years (interquartile range [IQR], 57 to 69 years), median number of prior therapies was 6 (IQR, 5 to 9), and median duration of follow-up was 5.4 months (IQR, 2.1 to 8.3 months). Most patients had both low pre-A ALC (75.3%) and pre-LD ALC (77.2%), and the reduction from pre-A to pre-LD (median, .65 to .55 × 10<sup>9</sup>/L) was statistically significant. Univariate analysis showed that the LD<sub>L</sub> + %R<sub>H</sub> group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LD<sub>L</sub> + %R<sub>L</sub> and LD<sub>N</sub> ALC groups (6-month PFS: 40% versus 67.6% and 60.9%; 6-month OS: 69.5% versus 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance; however, OS remained significantly worse for LD<sub>L</sub> + %R<sub>H</sub> group compared to the LD<sub>N</sub> ALC group (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.1 to 17), but the difference between the LD<sub>L</sub> + %R<sub>H</sub> versus %R<sub>L</sub> groups was not statistically significant (HR, 1.7; 95% CI, .8 to 4.0). Our findings indicate that low pre-LD ALC with high %R from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666636724004378/pdfft?md5=516a42e18a1fb9b4f30322163ccfb1a6&pid=1-s2.0-S2666636724004378-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.027
{"title":"Application of the Consensus Definition of Transplant Associated Thrombotic Microangiopathy (TA-TMA) Requires a More Expansive Lens to Accurately Diagnose and Risk Stratify Patients—Beware Reliance on Schistocytes Alone","authors":"","doi":"10.1016/j.jtct.2024.05.027","DOIUrl":"10.1016/j.jtct.2024.05.027","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262490","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.012
Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV1) threshold, focus on obstructive defects defined by FEV1/vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT.
{"title":"Diagnosis of Post-Hematopoietic Stem Cell Transplantation Bronchiolitis Obliterans Syndrome in Children: Time for a Rethink?","authors":"","doi":"10.1016/j.jtct.2024.05.012","DOIUrl":"10.1016/j.jtct.2024.05.012","url":null,"abstract":"<div><p>Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV<sub>1</sub>) threshold, focus on obstructive defects defined by FEV<sub>1</sub>/vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT.</p></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427700","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}
Pub Date : 2024-08-01DOI: 10.1016/S2666-6367(24)00507-4
{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(24)00507-4","DOIUrl":"10.1016/S2666-6367(24)00507-4","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961650","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.014
The implications of previous central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT) remain inadequately understood. Patients with CNS disease require more upfront CNS-directed intrathecal therapy, but little is known about whether transplant conditioning regimens should be intensified or if previous CNS involvement impacts post-HCT outcomes. While total body irradiation (TBI) remains standard for pediatric acute lymphoblastic leukemia myeloablative conditioning, it has been largely replaced with chemotherapy-only myeloablation in pediatric AML, primarily due to toxicity and late effects associated with TBI. In the setting of previous CNS involvement, it has been suggested that TBI-based myeloablation may have advantages due to superior CNS tissue penetration and thus decreased rates of AML relapse post-HCT. We analyzed a publicly available dataset derived from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry to characterize the impact of TBI in HCT preparative regimens in pediatric AML patients with a history of CNS involvement. The study dataset was obtained from the CIBMTR data repository. The study cohort included patients aged ≤21 years who underwent initial allogeneic HCT with myeloablative conditioning for de novo AML in the first or second complete remission (CR) between 2008 and 2016, who provided consent for research. Patients with mismatched related donor transplants and noncalcineurin inhibitor graft-versus-host disease (GVHD) prophylaxis were excluded. The dataset was further modified by excluding patients with missing disease site data or those with non-CNS extramedullary disease. Patients were categorized as CNS-positive or -negative AML (AML-CNS(+) and AML-CNS(−), respectively) based on the disease status at diagnosis. The Cox regression model and Fine-Grey methods were employed to delineate the effects of TBI and CNS disease on key HCT outcomes. The study cohort comprised 550 pediatric AML patients, of which 25% (n = 136) were AML-CNS(+). CNS involvement was more prevalent in patients aged 0 to 3 years, patients who were in the second CR, and those with a mismatched unrelated donor or umbilical cord blood. AML-CNS(+) patients demonstrated a lower relapse rate (hazard ratio: 0.50, 95% confidence interval: 0.33 to 0.76) compared to AML-CNS(−) patients, with comparable disease-free survival (DFS) and overall survival (OS) (P = .10 and 0.20, respectively) in the two cohorts. The entire TBI-treated cohort showed an association with increased risks of grade 2 to 4 acute GVHD, bloodstream infections, and endocrine dysfunction. TBI use within the AML-CNS(+) cohort was associated with a lower relapse rate but increased risks of nonrelapse mortality and a trend of higher grade 3 to 4 acute GVHD. In this population-based analysis of pediatric patients with de novo AML u
{"title":"Effects of Total Body Irradiation on Hematopoietic Cell Transplantation Outcomes in Pediatric Acute Myeloid Leukemia with Prior Central Nervous System Involvement","authors":"","doi":"10.1016/j.jtct.2024.05.014","DOIUrl":"10.1016/j.jtct.2024.05.014","url":null,"abstract":"<div><p><span>The implications of previous central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT) remain inadequately understood. Patients with CNS disease require more upfront CNS-directed intrathecal therapy, but little is known about whether transplant conditioning regimens should be intensified or if previous CNS involvement impacts post-HCT outcomes. While total body irradiation (TBI) remains standard for pediatric acute lymphoblastic leukemia myeloablative conditioning, it has been largely replaced with chemotherapy-only myeloablation in pediatric AML, primarily due to toxicity and late effects associated with TBI. In the setting of previous CNS involvement, it has been suggested that TBI-based myeloablation may have advantages due to superior CNS tissue penetration and thus decreased rates of AML relapse post-HCT. We analyzed a publicly available dataset derived from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry to characterize the impact of TBI in HCT preparative regimens in pediatric AML patients with a history of CNS involvement. The study dataset was obtained from the CIBMTR data repository. The study cohort included patients aged ≤21 years who underwent initial allogeneic HCT with myeloablative conditioning for de novo AML in the first or second complete remission (CR) between 2008 and 2016, who provided consent for research. Patients with mismatched related donor transplants and noncalcineurin inhibitor graft-versus-host disease (GVHD) prophylaxis were excluded. The dataset was further modified by excluding patients with missing disease site data or those with non-CNS extramedullary disease. Patients were categorized as CNS-positive or -negative AML (AML-CNS(+) and AML-CNS(−), respectively) based on the disease status at diagnosis. The Cox regression model and Fine-Grey methods were employed to delineate the effects of TBI and CNS disease on key HCT outcomes. The study cohort comprised 550 pediatric AML patients, of which 25% (</span><em>n</em> = 136) were AML-CNS(+). CNS involvement was more prevalent in patients aged 0 to 3 years, patients who were in the second CR, and those with a mismatched unrelated donor or umbilical cord blood. AML-CNS(+) patients demonstrated a lower relapse rate (hazard ratio: 0.50, 95% confidence interval: 0.33 to 0.76) compared to AML-CNS(−) patients, with comparable disease-free survival (DFS) and overall survival (OS) (<em>P</em><span> = .10 and 0.20, respectively) in the two cohorts. The entire TBI-treated cohort showed an association with increased risks of grade 2 to 4 acute GVHD<span>, bloodstream infections, and endocrine dysfunction. TBI use within the AML-CNS(+) cohort was associated with a lower relapse rate but increased risks of nonrelapse mortality and a trend of higher grade 3 to 4 acute GVHD. In this population-based analysis of pediatric patients with de novo AML u","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065643","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}
Pub Date : 2024-08-01DOI: 10.1016/j.jtct.2024.05.016
Most transplant-eligible multiple myeloma (MM) patients undergo autologous peripheral blood stem cell collection (PBSC) using G-CSF with on-demand plerixafor (G ± P). Chemomobilization (CM) can be used as a salvage regimen after G ± P failure or for debulking residual tumor burden ahead of autologous peripheral blood stem cell transplantation (ASCT). Prior studies utilizing cyclophosphamide-based CM have not shown long-term benefits. At our center, intensive CM (ICM) using a PACE- or HyperCVAD-based regimen has been used to mitigate “excessive” residual disease based on plasma cell (PC) burden or MM-related biomarkers. Given the lack of efficacy of non-ICM, we sought to determine the impact of ICM on event-free survival (EFS), defined as death, progressive disease, or unplanned treatment escalation. We performed a retrospective study of newly diagnosed MM patients who collected autologous PBSCs with the intent to proceed immediately to ASCT at our center between 7/2020 and 2/2023. Patients were excluded if they underwent a tandem autologous or sequential autologous-allogeneic transplant, had primary PC leukemia, received non-ICM treatment (i.e., cyclophosphamide and/or etoposide), or had previously failed G ± P mobilization. To appropriately evaluate the impact of ICM among those who potentially could have received it, we utilized a propensity score matching (PSM) approach whereby ICM patients were compared to a cohort of non-CM patients matched on pre-ASCT factors most strongly associated with the receipt of ICM. Of 451 patients identified, 61 (13.5%) received ICM (PACE-based, n = 45; hyper-CVAD-based, n = 16). Post-ICM/pre-ASCT, 11 patients (18%) required admission for neutropenic fever and/or infection. Among 51 evaluable patients, the overall response rate was 31%; however, 46 of 55 evaluable patients (84%) saw a reduction in M-spike and/or involved free light chains. Among those evaluated with longitudinal peripheral blood flow cytometry (n = 8), 5 patients (63%) cleared circulating blood PCs post-ICM. Compared to patients mobilized with non-CM, ICM patients collected a slightly greater median number of CD34+ cells (10.8 versus 10.2 × 10⁶/kg, P = .018). The median follow-up was 30.6 months post-ASCT. In a PSM multivariable analysis, ICM was associated with significantly improved EFS (hazard ratio [HR] 0.30, 95% CI 0.14 to 0.67, P = .003), but not improved OS (HR 0.38, 95% CI 0.10 to 1.44, P = .2). ICM was associated with longer post-ASCT inpatient duration (+4.1 days, 95% CI, 2.4 to 5.8, P < .001), more febrile days (+0.96 days, 95% CI 0.50 to 1.4, P < .001), impaired platelet engraftment (HR 0.23, 95% CI 0.06 to 0.87, P = .031), more bacteremia (OR 3.41, 95% CI 1.20 to 9.31, P = .018), and increased antibiotic usage (cefepime: +2.3 doses, 95% CI 0.39 to 4.1, P = .018; vancomycin: +1.0 doses, 95% CI 0.23 to 1.8, P
背景：大多数符合移植条件的多发性骨髓瘤（MM）患者接受自体外周血干细胞采集（PBSC），使用G-CSF和按需普利沙佛（G±P）。化学动员（CM）可作为G±P失败后的挽救方案，或在自体外周血干细胞移植（ASCT）前清除残余肿瘤负荷。之前使用环磷酰胺为基础的CM疗法的研究并未显示出长期疗效：在我们中心，使用基于PACE或HyperCVAD方案的强化CM（ICM）已被用于减轻基于浆细胞负荷或MM相关生物标志物的 "过度 "残留疾病。鉴于非强化CM缺乏疗效，我们试图确定ICM对无事件生存期（EFS）的影响，无事件生存期是指死亡、疾病进展或计划外治疗升级：我们对 2020 年 7 月至 2023 年 2 月期间在本中心采集了自体 PBSCs 并打算立即进行 ASCT 的新诊断 MM 患者进行了回顾性研究。如果患者接受了串联自体移植或序贯自体-异基因移植、患有原发性浆细胞白血病、接受了非ICM治疗（即环磷酰胺和/或依托泊苷）或之前G±P动员失败，则将其排除在外。为了适当评估 ICM 对那些有可能接受 ICM 的患者的影响，我们采用了倾向得分匹配 (PSM) 方法，将 ICM 患者与根据与接受 ICM 最密切相关的辅助检查前因素进行匹配的非 ICM 患者进行比较：在确定的 451 名患者中，61 人（13.5%）接受了 ICM（基于 PACE 的患者，45 人；基于 hyper-CVAD 的患者，16 人）。ICM 后/ASCT 前，11 名患者（18%）因中性粒细胞减少性发热和/或感染需要入院。在51名可评估的患者中，总反应率为31%；但在55名可评估的患者中，46名（84%）的M-棘和/或受累FLCs有所下降。在使用纵向外周血流式细胞术进行评估的患者（8 人）中，有 5 名患者（63%）在 ICM 后清除了循环血液中的 PC。与非 CM 动员的患者相比，ICM 患者收集的 CD34+ 细胞中位数略多（10.8 vs 10.2 × 10⁶/kg，p=.018）。ASCT后的中位随访时间为30.6个月。在 PSM 多变量分析中，ICM 与 EFS 的显著改善相关（HR 0.30，95% CI 0.14 至 0.67，p=.003），但与 OS 的改善无关（HR 0.38，95% CI 0.10 至 1.44，p=.2）。ICM与ASCT后住院时间延长有关（+4.1天，95% CI，2.4至5.8，p结论：在一项涉及接受辅助治疗前检查时疾病负担过重的 MM 患者的匹配分析中，ICM 与 EFS 的改善密切相关。这种益处是以延长住院时间、增加发热天数、增加菌血症发生率以及增加辅助治疗后抗生素用量为代价的。我们的研究结果表明，部分 MM 患者可以考虑使用 ICM，但必须谨慎权衡其使用与额外毒性之间的关系。
{"title":"Optimizing Autologous Stem Cell Transplantation in Multiple Myeloma: The Impact of Intensive Chemomobilization","authors":"","doi":"10.1016/j.jtct.2024.05.016","DOIUrl":"10.1016/j.jtct.2024.05.016","url":null,"abstract":"<div><p>Most transplant-eligible multiple myeloma (MM) patients undergo autologous peripheral blood stem cell collection (PBSC) using G-CSF with on-demand plerixafor (G ± P). Chemomobilization (CM) can be used as a salvage regimen after G ± P failure or for debulking residual tumor burden ahead of autologous peripheral blood stem cell transplantation (ASCT). Prior studies utilizing cyclophosphamide-based CM have not shown long-term benefits. At our center, intensive CM (ICM) using a PACE- or HyperCVAD-based regimen has been used to mitigate “excessive” residual disease based on plasma cell (PC) burden or MM-related biomarkers. Given the lack of efficacy of non-ICM, we sought to determine the impact of ICM on event-free survival (EFS), defined as death, progressive disease, or unplanned treatment escalation. We performed a retrospective study of newly diagnosed MM patients who collected autologous PBSCs with the intent to proceed immediately to ASCT at our center between 7/2020 and 2/2023. Patients were excluded if they underwent a tandem autologous or sequential autologous-allogeneic transplant, had primary PC leukemia, received non-ICM treatment (i.e., cyclophosphamide and/or etoposide), or had previously failed G ± P mobilization. To appropriately evaluate the impact of ICM among those who potentially could have received it, we utilized a propensity score matching (PSM) approach whereby ICM patients were compared to a cohort of non-CM patients matched on pre-ASCT factors most strongly associated with the receipt of ICM. Of 451 patients identified, 61 (13.5%) received ICM (PACE-based, <em>n</em> = 45; hyper-CVAD-based, <em>n</em> = 16). Post-ICM/pre-ASCT, 11 patients (18%) required admission for neutropenic fever and/or infection. Among 51 evaluable patients, the overall response rate was 31%; however, 46 of 55 evaluable patients (84%) saw a reduction in M-spike and/or involved free light chains. Among those evaluated with longitudinal peripheral blood flow cytometry (<em>n</em> = 8), 5 patients (63%) cleared circulating blood PCs post-ICM. Compared to patients mobilized with non-CM, ICM patients collected a slightly greater median number of CD34<sup>+</sup> cells (10.8 versus 10.2 × 10⁶/kg, <em>P</em> = .018). The median follow-up was 30.6 months post-ASCT. In a PSM multivariable analysis, ICM was associated with significantly improved EFS (hazard ratio [HR] 0.30, 95% CI 0.14 to 0.67, <em>P</em> = .003), but not improved OS (HR 0.38, 95% CI 0.10 to 1.44, <em>P</em> = .2). ICM was associated with longer post-ASCT inpatient duration (+4.1 days, 95% CI, 2.4 to 5.8, <em>P</em> < .001), more febrile days (+0.96 days, 95% CI 0.50 to 1.4, <em>P</em> < .001), impaired platelet engraftment (HR 0.23, 95% CI 0.06 to 0.87, <em>P</em> = .031), more bacteremia (OR 3.41, 95% CI 1.20 to 9.31, <em>P</em> = .018), and increased antibiotic usage (cefepime: +2.3 doses, 95% CI 0.39 to 4.1, <em>P</em> = .018; vancomycin: +1.0 doses, 95% CI 0.23 to 1.8, <em>P</","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071229","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}
Pub Date : 2024-08-01DOI: 10.1016/S2666-6367(24)00509-8
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(24)00509-8","DOIUrl":"10.1016/S2666-6367(24)00509-8","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961692","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}
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