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Imaging in Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome 肝静脉闭塞病/静脉窦阻塞综合征的影像学研究
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.016
Sherwin S. Chan , Antonio Colecchia , Rafael F. Duarte , Francesca Bonifazi , Federico Ravaioli , Jean Henri Bourhis

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation. Early diagnosis and, subsequently, earlier intervention have been shown to be beneficial to clinical outcomes. Diagnostic criteria from the European Society for Blood and Marrow Transplantation include recommendations on the use of imaging for diagnosis. This review discusses evidence on the use of imaging in the management of VOD/SOS and how imaging biomarkers can contribute to earlier diagnosis/treatment.

静脉闭塞性疾病/静脉窦阻塞综合征(VOD/SOS)是造血细胞移植的潜在威胁生命的并发症。早期诊断和随后的早期干预已被证明有利于临床结果。欧洲血液和骨髓移植协会的诊断标准包括使用影像学诊断的建议。这篇综述讨论了影像学在VOD/SOS治疗中的应用证据,以及影像学生物标志物如何有助于早期诊断/治疗。
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引用次数: 24
Guidelines for Cord Blood Unit Thaw and Infusion 脐带血解冻和输注指南
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.018
Andromachi Scaradavou , Scott T Avecilla , Joann Tonon , Ioannis Politikos , Mitchell E. Horwitz , Joanne Kurtzberg , Filippo Milano , Juliet N Barker , American Society for Transplantation and Cellular Therapy Cord Blood Special Interest Group
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引用次数: 4
Who Enrolls in an Online Cancer Survivorship Program? Reach of the INSPIRE Randomized Controlled Trial for Hematopoietic Cell Transplantation Survivors 谁报名参加在线癌症幸存者计划?INSPIRE对造血细胞移植幸存者的随机对照试验的影响
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.017
Jean C. Yi , Brie Sullivan , Wendy M. Leisenring , Navneet S. Majhail , Heather Jim , Alison Loren , Joseph Uberti , Victoria Whalen , Mary E.D. Flowers , Stephanie J. Lee , Katie Maynard , Karen L. Syrjala

The internet can be a valuable tool in delivering survivorship care to hematopoietic cell transplantation (HCT) cancer survivors. We describe the reach of INSPIRE, an Internet and social media-based randomized controlled trial, to address healthcare and psychosocial needs of HCT survivors. All survivors 2-10 years after HCT for hematologic malignancy or myelodysplasia from 6 transplantation centers in the US were approached by mail and follow-up calls. Eligible participants had access to the Internet, an email address, and did not have active disease in the past 2 years. We used logistic regression to determine characteristics of eligible survivors who were more or less likely to enroll. Of 2578 eligible HCT survivors, 1065 (41%) enrolled in the study. The mean age of enrollees was 56.3 ± 12.6 years (range, 19 to 89 years), 52% were male, and 94% were white. Survivors less likely to enroll included those who were male, age <40 years, and who received an autologous transplant (all P < .001). Compared with white survivors, African Americans were less likely to enroll (P < .001), whereas Native Americans/Alaska Natives were more likely to join the study (P = .03). The reach of the INSPIRE program was broad, including to survivors who traditionally have less access to resources, such as Native Americans/Alaskan Natives and rural residents. Strategies are still needed to improve the enrollment of online studies of survivorship resources for males, young adults, African American, and autologous HCT survivors because their use may improve outcomes.

互联网可以成为向造血细胞移植(HCT)癌症幸存者提供生存护理的宝贵工具。我们描述了INSPIRE的影响范围,这是一项基于互联网和社交媒体的随机对照试验,旨在解决HCT幸存者的医疗保健和心理社会需求。所有来自美国6个移植中心的血液恶性肿瘤或骨髓增生HCT后2-10年的幸存者通过邮件和随访电话联系。符合条件的参与者可以访问互联网,使用电子邮件地址,并且在过去两年内没有活动性疾病。我们使用逻辑回归来确定符合条件的幸存者或多或少可能入组的特征。在2578名符合条件的HCT幸存者中,1065名(41%)参加了这项研究。入组者的平均年龄为56.3±12.6岁(19 ~ 89岁),52%为男性,94%为白人。不太可能入组的幸存者包括年龄在40岁的男性和接受了自体移植的患者(均为P <措施)。与白人幸存者相比,非裔美国人报名参加的可能性更低(P <.001),而美国原住民/阿拉斯加原住民更有可能加入研究(P = .03)。INSPIRE项目的影响范围很广,包括传统上很少获得资源的幸存者,如美国原住民/阿拉斯加原住民和农村居民。对于男性、年轻人、非裔美国人和自体HCT幸存者,仍然需要策略来提高在线研究幸存者资源的登记,因为它们的使用可能会改善结果。
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引用次数: 6
Officers and Directors of ASTCT ASTCT的官员和董事
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/S1083-8791(20)30548-6
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引用次数: 0
Fludarabine, Campath, and Low-Dose Cyclophosphamide (FCClow) with or without TBI Conditioning Results in Excellent Transplant Outcomes in Children with Severe Aplastic Anemia 氟达拉滨、Campath和低剂量环磷酰胺(fclow)伴或不伴TBI调节可使重度再生障碍性贫血儿童移植预后良好
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.027
Ravi M. Shah , Tony H. Truong , Michel T. Leaker , Nicola A.M. Wright , Doan Le , MacGregor Steele , Aisha A.K. Bruce , Sunil Desai , Gregory M.T. Guilcher , Victor Lewis

Various reduced-intensity conditioning regimens are in use for allogeneic hematopoietic cell transplant (HSCT) in patients with idiopathic severe aplastic anemia (SAA). We describe the use of fludarabine, Campath, and low-dose cyclophosphamide (FCClow) conditioning in 15 children undergoing related or unrelated donor transplants. Total body irradiation (TBI) of 2 Gy was added for unrelated donor HSCT. At a median follow-up of 2.3 years, the failure-free survival was 100%, with low rates of infection and toxicity. There was no occurrence of grade III to IV acute graft-versus-host disease (GVHD). All patients had full donor myeloid chimerism post-HSCT, even with mixed chimerism in the T cell lineage. The absence of chronic GVHD and long-term stable mixed donor T cell chimerism confirms immune tolerance following FCClow (± TBI) conditioned transplantation in children with SAA.

各种降低强度调理方案用于特发性严重再生障碍性贫血(SAA)患者的异基因造血细胞移植(HSCT)。我们描述了15名接受相关或非相关供体移植的儿童使用氟达拉滨、Campath和低剂量环磷酰胺(fclow)调节。非亲属供体HSCT增加2gy的全身照射(TBI)。中位随访时间为2.3年,无失败生存率为100%,感染和毒性发生率低。未发生III至IV级急性移植物抗宿主病(GVHD)。所有患者在造血干细胞移植后都有完全的供体骨髓嵌合,甚至在T细胞谱系中有混合嵌合。慢性GVHD的缺失和长期稳定的混合供体T细胞嵌合证实了儿童SAA在FCClow(±TBI)条件移植后的免疫耐受。
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引用次数: 4
Impact of Preemptive Therapy for Cytomegalovirus on Hospitalizations and Cost after Hematopoietic Stem Cell Transplantation 巨细胞病毒先发制人治疗对造血干细胞移植后住院和费用的影响
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.025
Jiaqi Fang , Yiqi Su , Phaedon D. Zavras , Amit D. Raval , Yuexin Tang , Miguel-Angel Perales , Sergio Giralt , Anat Stern , Genovefa A. Papanicolaou

Cytomegalovirus (CMV) viremia occurs in 40% to 80% of CMV-seropositive (R+) recipients of allogeneic hematopoietic cell transplantation (HCT). The preemptive therapy (PET) strategy has reduced the risk of CMV end-organ disease (EOD) and associated mortality but may lead to substantial healthcare resource utilization (HCRU) and costs. Real-world data on the economic impact of PET is relevant for the evaluation of alternative strategies for CMV management. We examined the impact of clinically significant CMV treated with PET on inpatient length of stay (LOS), number of readmissions, and associated costs from day 0 through day 180 post-HCT.

This was a retrospective study of R+ adults who underwent peripheral blood or marrow allogeneic HCT at Memorial Sloan Kettering Cancer Center between March 2013 and December 2017. Patients were routinely screened for CMV by qPCR and received PET according to institutional standards of care. Data were extracted from electronic medical records and hospital databases. Itemized cost data per patient were obtained from the Vizient database, adjusted to 2017 dollars using inflation indices. Study outcomes included HCRU evaluated by inpatient LOS and inpatient cost in patients who received PET for clinically significant CMV (PET group) compared with those who did not receive PET (no PET group) and the frequency and cost of CMV-related readmissions compared with non CMV-related readmissions. We used generalized linear models to examine the incremental HCRU and costs associated with PET controlling for other potential factors. Of 357 patients, PET was initiated in 208 (58.3%), at a median of 35 days after HCT. By day 180, 23 patients (6.4%) had developed CMV EOD and 3 (.8%) had died of CMV. Compared with the no PET group, the PET group had a longer LOS for HCT admission (P = .0276), longer total LOS by day 180 (P = .0001), a higher number of readmissions (P = .0001), a higher mean inpatient cost for HCT admission ($189,389 versus $151,646; P = .0133), and a higher total inpatient cost ($297,563 versus $205,815; P < .0001). Among PET recipients, CMV-related readmissions were associated with higher mean cost per episode compared with non CMV-related readmissions ($165,455 versus $89,419; P = .005). CMV-related readmissions comprised 40.6% of total all-cause readmissions and incurred 55.9% of total all-cause readmission costs in PET recipients. Our data show that patients treated with currently available PET had greater inpatient HCRU and cost, by day 180 compared with patients who did not receive PET. The cost of CMV-related readmissions accounted for 56% of total readmission cost among PET recipients. Future studies are needed to examine the cost-effectiveness of alternative strategies for CMV management.

巨细胞病毒(CMV)病毒血症发生在40%至80%的巨细胞病毒血清阳性(R+)受体异体造血细胞移植(HCT)。先发制人治疗(PET)策略降低了巨细胞病毒终末器官疾病(EOD)和相关死亡率的风险,但可能导致大量的医疗资源利用(HCRU)和成本。关于PET经济影响的真实数据与CMV管理替代策略的评估相关。我们研究了经PET治疗的具有临床意义的巨细胞病毒对hct后第0至180天住院时间(LOS)、再入院次数和相关费用的影响。这是一项回顾性研究,研究对象为2013年3月至2017年12月期间在纪念斯隆凯特琳癌症中心接受外周血或骨髓同种异体HCT的R+成人。患者通过qPCR常规筛查巨细胞病毒,并根据机构护理标准接受PET。数据提取自电子病历和医院数据库。每位患者的逐项成本数据来自Vizient数据库,使用通胀指数调整为2017年美元。研究结果包括HCRU通过住院LOS和住院费用来评估接受PET治疗临床显著巨细胞病毒患者(PET组)与未接受PET治疗患者(未接受PET组)的HCRU,以及CMV相关再入院的频率和费用与非CMV相关再入院的比较。我们使用广义线性模型来检验与PET控制其他潜在因素相关的HCRU增量和成本。在357例患者中,208例(58.3%)在HCT后35天开始PET治疗。到第180天,23例(6.4%)发生巨细胞病毒EOD, 3例(0.8%)死于巨细胞病毒。与无PET组相比,PET组HCT入院时的住院时间更长(P = 0.0276), 180天的总住院时间更长(P = 0.0001),再入院次数更多(P = 0.0001), HCT入院的平均住院费用更高(189,389美元对151,646美元;P = 0.0133),住院总费用较高(297,563美元对205,815美元;P & lt;。)。在PET接受者中,与非cmv相关的再入院相比,cmv相关的再入院与每集平均费用较高相关(165,455美元对89,419美元;p = .005)。cmv相关再入院占PET患者全因再入院总费用的40.6%,占全因再入院总费用的55.9%。我们的数据显示,与未接受PET治疗的患者相比,接受目前可用PET治疗的患者在180天的住院HCRU和费用更高。与cmv相关的再入院费用占PET接受者总再入院费用的56%。未来的研究需要检验CMV管理的替代策略的成本效益。
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引用次数: 12
Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation 难治性和17p缺失的慢性淋巴细胞白血病:途径抑制剂和异体干细胞移植改善生存
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.032
L. Farina , F. Barretta , L. Scarfò , B Bruno , F. Patriarca , AM. Frustaci , M. Coscia , C. Salvetti , G. Quaresmini , R. Fanin , F. Onida , M. Magagnoli , F. Zallio , D. Vallisa , G. Reda , A Ferrario , P. Corradini , M Montillo

Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients.

难治性/早期复发性和17p缺失/p53突变(del(17p)/TP53mut)阳性的慢性淋巴细胞白血病(CLL)一直被认为是一种高风险疾病,可能适合同种异体干细胞移植(alloSCT)治疗。在这项涉及157例患者的多中心回顾性分析中,我们比较了接受同种异体细胞移植、b细胞受体途径抑制剂(BCRi)和两者治疗的高危CLL患者的结果。71例患者接受BCRis治疗,67例患者接受低强度调节同种异体细胞移植,19例患者在移植前后接受同种异体细胞移植和BCRi。采用治疗加权逆概率分析比较同种异体移植组和非同种异体移植组;在两组中,5年OS、PFS和累计非复发死亡率(NRM)和复发率分别为40%对60% (P = .096)、34%对17% (P = .638)、28%对5% (P = .016)、38%对83% (P = .005)。接受同种异体细胞移植+ BCRi治疗的患者3年总生存率为83%。包括接受BCRi治疗的患者在内,同种异体移植的3年OS和NRM在2000 - 2007年分别为53%和17%,2008 - 2012年分别为55%和30%,2013 - 2018年分别为72%和18%。综上所述,途径抑制剂联合同种异体细胞移植是可行的,并可能进一步改善高危CLL患者的预后。
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引用次数: 4
Global Metabolomics in Allogeneic Hematopoietic Cell Transplantation Recipients Discordant for Chronic Graft-versus-Host Disease 慢性移植物抗宿主病的异基因造血细胞移植受体的整体代谢组学不一致
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.014
Debra Lynch Kelly , Nosha Farhadfar , Angela Starkweather , Timothy J Garrett , Yingwei Yao , John R. Wingard , Iqbal Mahmud , Victoria Menzies , Param Patel , Karima M. Alabasi , Debra Lyon

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

慢性移植物抗宿主病(cGVHD)仍然是异基因造血细胞移植(同种异体造血细胞移植)幸存者的一个重要的晚期效应问题,导致发病率和死亡率。cGVHD的病因尚不清楚。由于缺乏早期诊断测试和病理生理学的模糊性,有针对性的治疗仍然有限。预测、控制反应或预测的生物标志物尚未确定。代谢组学,即代谢物的量化,是cGVHD的潜在生物标志物,但尚未在该人群中进行评估。在这项研究中,我们检测了储存血浆的整体代谢物,以鉴定同种异体hct后cGVHD不一致个体的差异表达代谢物。采用描述性、对比性、横断面研究设计,对来自两项亲本研究的40名成人同种异体hct受体(20名cGVHD患者和20名非cGVHD患者)血浆样本中代谢物的差异表达进行了检测。代谢组学分析在佛罗里达大学东南综合代谢组学中心进行。完整的实验方法遵循先前发表的方法。所有统计分析均由博士学位准备,训练有素的生物信息学统计学家进行。在cGVHD患者和非cGVHD患者之间有10种代谢物表达差异。差异代谢物包括与能量代谢(n = 3)、氨基酸代谢(n = 3)、脂质代谢(n = 2)、咖啡因代谢(n = 1)和神经传递(n = 1)相关的代谢物,其中血清素的倍数变化最大(21.01)。这项研究表明,cGVHD可能与细胞能量扩大和潜在的线粒体功能障碍有关。cGVHD患者和非cGVHD患者之间的代谢谱差异表明,代谢扰动值得进一步探索,作为cGVHD的潜在生物标志物。这些发现支持了进一步研究的需要,通过更大的前瞻性研究设计来确定代谢组学危险因素,这些因素可能表明需要早期预防措施和早期治疗来降低cGVHD。
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引用次数: 7
Splenomegaly May Increase the Risk of Rejection in Low-Risk Matched Related Donor Transplant for Thalassemia, This Risk Can Be Partially Overcome by Additional Immunosuppression during Conditioning 脾大可能增加地中海贫血低风险匹配相关供体移植的排斥风险,这种风险可以通过调节期间额外的免疫抑制部分克服
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.013
Stalin Ramprakash , C.P. Raghuram , Priya Marwah , Rajpreet Soni , Deepa Trivedi , Sadaf Khalid , Naila Yaqub , Fatima Itrat , Sarah Khan Gilani , Tatheer Zahra , Rakesh Dhanya , Rajat Kumar Agarwal , Lawrence Faulkner

Severe thalassemia syndromes (ST) are highly curable by bone marrow transplant (BMT), but rejection may still occur. We retrospectively analyzed our fully matched related donor transplants to establish if isolated splenomegaly is an independent risk factor for rejection and if this risk can be reduced by modifying the conditioning protocol. In this study, we compared rejection rates between patients with and without splenomegaly in 189 consecutive low-risk ST transplants across 2 sequential conditioning regimens: regimen A (August 2013 to December 2016): busulfan (14 mg/kg oral, not adjusted to serum levels), cyclophosphamide (200 mg/kg), and anti-thymocyte globulin (ATG) (Genzyme (Sanofi, Paris, France) 4 mg/kg or Fresenius (Grafalon, Neovii Biotech GmbH, Gräfelfing Germany) 16 mg/kg on days –12 to –10), and regimen B: same backbone as regimen A except fludarabine total dose of 150 mg was added upfront and ATG dose was increased to 7 mg/kg in case of splenomegaly and/or sex-mismatched transplants (January 2017 to September 2018). Compared with regimen A, in regimen B, both overall rejection rates (RRs) (16% versus 6.5%, P = .023) and treatment-related mortality (TRM) (9.9% versus 2.8%, P = .038) improved significantly. By Cox regression analysis, the improvement in RR between the 2 protocols was particularly significant in patients with splenomegaly (RR 54.5% versus 6.5%, P = .00015; TRM 18.2% versus 6.5%, P = .25) (hazard ratio, 4.13; confidence interval, 1.61 to 10.6; P = .003). The increased risk of rejection related to splenomegaly can be overcome by adding fludarabine to the standard ATG-Busulfan- Cyclophosphamide (ATG-Bu-Cy) protocol without significantly increasing transplant-related morbidity and mortality or resorting to splenectomy pre-BMT.

严重地中海贫血综合征(ST)可通过骨髓移植(BMT)高度治愈,但仍可能发生排斥反应。我们回顾性分析了完全匹配的相关供体移植,以确定孤立性脾肿大是否是排斥反应的独立危险因素,以及是否可以通过修改条件方案来降低这种风险。在这项研究中,我们比较了189例连续低风险ST移植患者的脾肿大和非脾肿大患者在2个顺序调节方案中的排异率:方案A(2013年8月至2016年12月):busulfan(口服14mg /kg,未调整到血清水平)、环磷酰胺(200mg /kg)和抗胸腺细胞球蛋白(ATG) (Genzyme (Sanofi, Paris, France) 4mg /kg或Fresenius (Grafalon, Neovii Biotech GmbH, Gräfelfing德国)16mg /kg,第12天至第10天),方案B。2017年1月至2018年9月,在脾大和/或性别不匹配移植的情况下,前期增加氟达拉滨总剂量150 mg, ATG剂量增加至7 mg/kg,与方案A相同。与方案A相比,方案B的总排斥率(RRs)(16%对6.5%,P = 0.023)和治疗相关死亡率(TRM)(9.9%对2.8%,P = 0.038)均显著改善。Cox回归分析显示,两种治疗方案在脾肿大患者中的RR改善尤为显著(RR分别为54.5%和6.5%,P = 0.00015;TRM为18.2%对6.5%,P = 0.25)(风险比4.13;置信区间为1.61 ~ 10.6;p = .003)。通过在标准ATG-Busulfan- Cyclophosphamide (ATG-Bu-Cy)方案中加入氟达拉滨,可以克服脾大相关排斥反应风险的增加,而不会显著增加移植相关的发病率和死亡率,也不会在bmt前进行脾切除术。
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引用次数: 2
Chimeric Antigen Receptor Therapy: How Are We Driving in Solid Tumors? 嵌合抗原受体治疗:我们如何在实体肿瘤中驱动?
IF 4.3 Q1 Medicine Pub Date : 2020-10-01 DOI: 10.1016/j.bbmt.2020.06.020
Uri Greenbaum , Fevzi F. Yalniz , Samer A. Srour , Katayoun Rezvani , Harjeet Singh , Amanda Olson , George Blumenschein Jr , David S. Hong , Elizabeth J. Shpall , Partow Kebriaei

Immune effector cell (IEC) therapy is emerging as a promising approach in the field of cancer immunotherapy. Clinical IEC trials, predominantly using chimeric antigen receptor (CAR) T cells, have shown excellent responses in CD19+ B cell malignancies and multiple myeloma. In solid tumors, preclinical data are encouraging, but clinical data are in their infancy, and there are challenges in using CAR T therapy in this setting, including (1) on-target off-tumor toxicity, (2) optimal target identification, (3) effective trafficking into bulky tumor tissue, and (4) resistance to tumor immune evasion mechanisms.

Novel techniques and modifications are being explored in both the preclinical and clinical settings, aiming to improve treatment efficacy and address the aforementioned obstacles to successful CAR T therapy in solid tumors. Here we review these challenges in a clinically oriented approach and summarize published clinical trials using CAR T therapy in a variety of solid tumors.

免疫效应细胞(IEC)治疗是肿瘤免疫治疗领域的一种很有前途的方法。临床IEC试验主要使用嵌合抗原受体(CAR) T细胞,在CD19+ B细胞恶性肿瘤和多发性骨髓瘤中显示出良好的应答。在实体瘤中,临床前数据令人鼓舞,但临床数据尚处于起步阶段,在这种情况下使用CAR - T疗法存在挑战,包括(1)靶外肿瘤毒性,(2)最佳靶点识别,(3)有效运输到庞大的肿瘤组织,以及(4)抵抗肿瘤免疫逃避机制。新的技术和改进正在临床前和临床环境中进行探索,旨在提高治疗效果并解决上述阻碍CAR - T治疗实体瘤成功的障碍。在这里,我们以临床为导向的方法回顾了这些挑战,并总结了在各种实体瘤中使用CAR - T疗法的已发表的临床试验。
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引用次数: 7
期刊
Biology of Blood and Marrow Transplantation
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