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Goal-Oriented Monitoring of Cyclosporine Is Effective for Graft-versus-Host Disease Prevention after Hematopoietic Stem Cell Transplantation in Sickle Cell Disease and Thalassemia Major 定向监测环孢素对镰状细胞病和重度地中海贫血患者造血干细胞移植后移植物抗宿主病预防有效
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.01.016
Alexandra Gauthier , Nathalie Bleyzac , Nathalie Garnier , Kamila Kebaili , Philippe Joly , Marie-Pierre Goutagny , Isabelle Mollet , Sylvain Goutelle , Cécile Renard , Yves Bertrand

Graft-versus-host disease (GVHD) is an important challenge and a major cause of morbidity and mortality in children after hematopoietic stem cell transplant (HSCT). Herein we report our institution's experience of goal-oriented Bayesian monitoring for cyclosporine (CsA) used alone as GVHD prophylaxis during the post-transplant period in pediatric patients with thalassemia major (TM) or sickle cell anemia (SCA) undergoing HLA-matched HSCT. We also studied evolution of chimerism. Twenty-six consecutive patients (SCA, 14; TM, 12) underwent matched sibling donor (MSD) HSCT from 2004 to 2014. All patients received a myeloablative conditioning regimen. GVHD prophylaxis consisted of 20 mg/kg antithymocyte globulin in the conditioning regimens and then CsA alone in the post-transplant period. Target CsA trough blood concentration (TBC) was 150 ± 20 ng/mL. At last follow-up, all patients were alive and free of disease, even in cases of mixed chimerism. Engraftment occurred in all patients. No patient developed grades II to IV acute GVHD, 4 patients developed acute grade I skin GVHD, and only 1 presented with chronic pulmonary GVHD. A better control of GVHD and immunosuppression by a strict monitoring of CsA TBC as described herein is promising and could play a crucial role. Further investigations are required, but this study opens new perspectives to improve survival and safety of HSCT from alternative donors in TM and SCA to levels compatible with that obtained with MSDs.

移植物抗宿主病(GVHD)是儿童造血干细胞移植(HSCT)后发病和死亡的一个重要挑战和主要原因。在此,我们报告了本机构在接受hla匹配的HSCT的患有地中海贫血(TM)或镰状细胞贫血(SCA)的儿童患者移植后单独使用环孢素(CsA)作为GVHD预防的目标导向贝叶斯监测的经验。我们也研究了嵌合的进化。26例连续患者(SCA, 14例;2004年至2014年,12例患者接受了兄弟姐妹匹配供体(MSD) HSCT。所有患者均接受清髓调理方案。GVHD预防包括在调节方案中使用20 mg/kg抗胸腺细胞球蛋白,然后在移植后单独使用CsA。靶CsA血药浓度(TBC)为150±20 ng/mL。在最后的随访中,即使是混合嵌合的病例,所有患者都存活且无疾病。所有患者均有移植。没有患者发展为II至IV级急性GVHD, 4例患者发展为急性I级皮肤GVHD,仅有1例患者表现为慢性肺GVHD。本文所述的通过严格监测CsA TBC来更好地控制GVHD和免疫抑制是有希望的,并且可能发挥关键作用。需要进一步的研究,但这项研究为提高TM和SCA中替代供体的HSCT的存活率和安全性提供了新的视角,使其达到与MSDs相容的水平。
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引用次数: 3
Pre-Hematopoietic Stem Cell Transplantation Lung Computed Tomography as an Alternative to the Pulmonary Function Test during the COVID-19 Pandemic 在COVID-19大流行期间,造血前干细胞移植肺部计算机断层扫描作为肺功能测试的替代方案
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.025
Masaharu Tamaki , Hideki Nakasone , Tadao Aikawa , Yuhei Nakamura , Masakatsu Kawamura , Shunto Kawamura , Junko Takeshita , Nozomu Yoshino , Yukiko Misaki , Kazuki Yoshimura , Shinpei Matsumi , Ayumi Gomyo , Aki Tanihara , Machiko Kusuda , Yu Akahoshi , Shun-ichi Kimura , Shinichi Kako , Noriko Oyama-Manabe , Yoshinobu Kanda

The pulmonary function test (PFT) is an important test for risk stratification before allogeneic transplantation (allo-HCT). However, it might be preferable to avoid PFT as much as possible in the recent era of coronavirus disease 2019 (COVID-19), because PFT requires forced expirations and might produce aerosols, increasing the risk of COVID-19 transmission. Therefore, we tried to predict normal PFT results before allo-HCT based on computed tomography (CT) findings. This study included 390 allo-HCT recipients at our center for whom lung CT images and PFT results before allo-HCT were available. Abnormal CT findings were less likely to be observed in the normal PFT group (47.0% versus 67.4%, P = .015), with a high negative predictive value of 92.9%. In a multivariate analysis, normal CT was significantly associated with normal PFT (odds ratio, 2.47; 95% confidence interval, 1.22 to 4.97; P = .012). A model for predicting normal PFT was constructed based on the results of a multivariate analysis, and the area under the curve of the receiver operating characteristic analysis was 0.656, which gave a sensitivity of 45.5% and a specificity of 86.0%. The relatively high specificity of the model suggested that PFT can be omitted in patients with normal CT findings before allo-HCT.

肺功能检查(PFT)是同种异体移植(alloc - hct)前危险分层的重要检查。然而,在最近的2019冠状病毒病(COVID-19)时代,最好尽可能避免PFT,因为PFT需要强制过期,并且可能产生气溶胶,增加了COVID-19传播的风险。因此,我们试图根据计算机断层扫描(CT)的结果来预测同种异体hct前的正常PFT结果。本研究纳入了我们中心的390名接受同种异体hct治疗的患者,他们在接受同种异体hct之前的肺部CT图像和PFT结果都是可用的。PFT正常组CT异常表现较少(47.0% vs 67.4%, P = 0.015),阴性预测值为92.9%。在多变量分析中,正常CT与正常PFT显著相关(优势比,2.47;95%置信区间为1.22 ~ 4.97;p = .012)。基于多变量分析的结果,建立了正常PFT预测模型,受试者工作特征分析曲线下面积为0.656,敏感性为45.5%,特异性为86.0%。该模型的相对高特异性表明,在同种异体CT前CT表现正常的患者可以忽略PFT。
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引用次数: 2
Officers and Directors of ASTCT ASTCT的官员和董事
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/S1083-8791(20)30705-9
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引用次数: 0
Nonmyeloablative Conditioning Regimen before T Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Hodgkin and Non-Hodgkin Lymphomas 晚期霍奇金淋巴瘤和非霍奇金淋巴瘤的移植后环磷酰胺T细胞单倍体移植前非清髓调节方案
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.014
Catalina Montes de Oca , Luca Castagna , Chiara De Philippis , Stefania Bramanti , Jean Marc Schiano , Thomas Pagliardini , Aude Collignon , Samia Harbi , Jacopo Mariotti , Angela Granata , Valerio Maisano , Sabine Furst , Faezeah Legrand , Christian Chabannon , Carmelo Carlo-Stella , Armando Santoro , Didier Blaise , Raynier Devillier

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a valid option in patients with refractory lymphomas. HLA haploidentical stem cell transplantation (haplo-SCT) expanded the accessibility to allogeneic hematopoietic cell transplantation. The aims of study were to retrospectively assess the toxicity and efficacy of haplo-SCT using nonmyeloablative conditioning in patients with advanced lymphoma. In total, 147 patients with advanced lymphoma at 2 partner institutions were included. Patients received a uniform nonmyeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis. The primary endpoints were progression-free survival (PFS), overall survival (OS), GVHD, nonrelapse mortality, and GVHD, relapse-free survival (GRFS). Median follow-up was 39 months (range, 6 to 114 months). The median age was 46 years (range, 19 to 71 years). Sixty-five percent of patients were in complete remission (CR) at transplantation. Cumulative incidence of grade II to IV acute GVHD was 30% (95% confidence interval [Cl], 23% to 38%). Two-year cumulative incidence of all grades of chronic GVHD was 13% (95% CI, 8% to 20%). Two-year cumulative incidence of disease relapse was 19% (95% CI, 14% to 27%), with a higher incidence in patients not being in CR at allo-HCT (CR versus not CR: 12% versus 33%, P = .006). Two-year PFS, OS, and GRFS were 66% (95% CI, 59-75), 73% (95% CI, 66-81), and 56% (95% CI, 48-65), respectively. Haplo-SCT with post-transplantation cyclophosphamide may be considered a valid option for patients with aggressive lymphoma and deserves further evaluation.

同种异体造血干细胞移植是治疗难治性淋巴瘤的有效方法。HLA单倍体干细胞移植(haploo - sct)扩大了异体造血细胞移植的可及性。本研究的目的是回顾性评估晚期淋巴瘤患者采用非清髓性条件下单倍体细胞移植的毒性和疗效。共纳入2家合作机构147例晚期淋巴瘤患者。患者接受统一的非清髓性调节方案和移植物抗宿主病(GVHD)预防。主要终点为无进展生存期(PFS)、总生存期(OS)、GVHD、非复发死亡率和GVHD、无复发生存期(GRFS)。中位随访为39个月(6至114个月)。中位年龄为46岁(范围19 - 71岁)。65%的患者移植后完全缓解(CR)。II级至IV级急性GVHD的累积发病率为30%(95%可信区间[Cl], 23%至38%)。所有级别慢性GVHD的两年累积发病率为13% (95% CI, 8% - 20%)。两年累积疾病复发率为19% (95% CI, 14% - 27%),在异位hct时未处于CR的患者中发病率更高(CR vs非CR: 12% vs 33%, P = 0.006)。两年PFS、OS和GRFS分别为66% (95% CI, 59-75)、73% (95% CI, 66-81)和56% (95% CI, 48-65)。单倍体sct移植后环磷酰胺可能被认为是侵袭性淋巴瘤患者的有效选择,值得进一步评估。
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引用次数: 4
Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma 无丙二醇Melphalan与PG-Melphalan对骨髓瘤自体造血细胞移植的调节作用。
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.030
Kathleen Monahan , Ariel Kleman , Bicky Thapa , Aniko Szabo , Anita D'Souza , Binod Dhakal , James H. Jerkins , Marcelo C. Pasquini , Mehdi Hamadani , Parameswaran N. Hari , Saurabh Chhabra

High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard of care for patients with transplantation-eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution, leading to the use of propylene glycol (PG) as a solubilizing agent. A newer PG-free Mel preparation (Evomela) uses beta cyclodextrin captisol as a solubilizing agent and was approved by the United States Food and Drug Administration as a conditioning agent based on a single-phase IIb study showing bioequivalence. We compared the outcomes of consecutive patients with myeloma undergoing autoHCT using the 2 formulations of Mel for conditioning as our center switched from using the older formulation (PG-Mel) to the newer one (PGF-Mel). Of 294 autoHCT recipients, 162 received PG-Mel conditioning and 132 received PGF-Mel conditioning. The PGF-Mel group was older and had a lower average Karnofsky Performance Status score. PGF-Mel was associated with faster neutrophil recovery (median, 12 days versus 13 days; P < .001), fewer grade 3-4 infections within 30 days of autoHCT (1.5% versus 8.0%; P = .048), and a lower 30-day rehospitalization rate (6.8% versus 17.9%; P = .04), as confirmed by propensity-weighted analysis. No significant between-group differences were detected in mucositis, organ toxicity, myeloma response, or 100-day mortality.

自体造血细胞移植(autoHCT)前大剂量美法兰(Mel)调理是适合移植的多发性骨髓瘤患者的标准治疗方法。传统的冻干梅尔配方在重组后的溶解度和稳定性不足,导致使用丙二醇(PG)作为增溶剂。一种新的不含pg的Mel制剂(Evomela)使用-环糊精captisol作为增溶剂,并被美国食品和药物管理局批准作为调理剂,基于一项显示生物等效性的单相IIb研究。我们比较了连续接受自体hct的骨髓瘤患者使用两种配方的Mel进行调节的结果,我们的中心从使用旧配方(PG-Mel)切换到使用新配方(PGF-Mel)。在294例自体hct受体中,162例接受PG-Mel调节,132例接受PGF-Mel调节。PGF-Mel组年龄较大,平均Karnofsky表现状态评分较低。PGF-Mel与更快的中性粒细胞恢复相关(中位数,12天对13天;P & lt;.001), 30天内3-4级感染较少(1.5%对8.0%;P = 0.048), 30天再住院率较低(6.8%对17.9%;P = .04),倾向加权分析证实了这一点。在粘膜炎、器官毒性、骨髓瘤反应或100天死亡率方面,两组间无显著差异。
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引用次数: 2
Clinical and Neuroimaging Correlates of Post-Transplant Delirium 移植后谵妄的临床和神经影像学相关性
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.09.016
Patrick Smith , Jillian C. Thompson , Elena Perea , Brian Wasserman , Lauren Bohannon , Alessandro Racioppi , Taewoong Choi , Cristina Gasparetto , Mitchell E. Horwitz , Gwynn Long , Richard Lopez , David A. Rizzieri , Stefanie Sarantopoulos , Keith M. Sullivan , Nelson J. Chao , Anthony D. Sung

Delirium is common among adults undergoing hematopoietic stem cell transplantation (HCT), although the clinical and neuroimaging correlates of post-HCT delirium have not been adequately delineated. We therefore examined the frequency of delirium and neuroimaging correlates of post-transplant delirium in a retrospective cohort of 115 adults undergoing neuroimaging after allogeneic HCT. Delirium was established using previously validated methods for retrospective identification of chart-assessed postprocedural delirium. Chart reviews were independently conducted by a multidisciplinary team with expertise in HCT, psychiatry, and psychology on consecutive allogeneic HCT patients who underwent neuroimaging assessments and transplantation at a single center between January 2009 and December 2016. Neuroimaging markers of white matter damage and brain volume loss were also recorded. In total, 115 patients were included, ranging in age from 20 to 74 years (mean [SD] age, 49 [13]). Fifty-three patients (46%) developed post-HCT delirium. In an adjusted model, delirium incidence was associated with older age (odds ratio [OR], 1.92 [1.28, 2.87] per decade, P = .002), greater severity of white matter hyperintensities (OR, 1.95 [1.06, 3.57], P = .031), and conditioning intensity (OR, 6.37 [2.20, 18.45], P < .001) but was unrelated to cortical atrophy (P = .777). Delirium was associated with fewer hospital-free days (P = .023) but was not associated with overall survival (hazard ratio, 0.95 [0.56, 1.61], P = .844). Greater incidence of delirium following HCT was associated with greater age, microvascular burden, and conditioning intensity. Pre-HCT consideration of microvascular burden and other neuroimaging biomarkers of risk may be warranted.

谵妄在接受造血干细胞移植(HCT)的成年人中很常见,尽管HCT后谵妄的临床和神经影像学相关因素尚未得到充分的描述。因此,我们对115名接受同种异体HCT后神经影像学检查的成年人进行回顾性队列研究,检查了移植后谵妄的频率和神经影像学相关因素。谵妄是使用先前验证的方法来回顾性鉴定经图表评估的术后谵妄。2009年1月至2016年12月,一个具有HCT、精神病学和心理学专业知识的多学科团队对在同一中心连续接受神经影像学评估和移植的同种异体HCT患者进行了独立的图表审查。同时记录脑白质损伤和脑容量损失的神经影像学指标。共纳入115例患者,年龄20 ~ 74岁(平均[SD]年龄49岁[13])。53例患者(46%)出现hct后谵妄。在一个调整后的模型中,谵妄的发病率与年龄较大(比值比[OR],每十年1.92 [1.28,2.87],P = 0.002)、白质高信号的严重程度(OR, 1.95 [1.06, 3.57], P = 0.031)和调节强度(OR, 6.37 [2.20, 18.45], P <.001),但与皮质萎缩无关(P = .777)。谵妄与较少的无院天数相关(P = 0.023),但与总生存率无关(风险比,0.95 [0.56,1.61],P = 0.844)。HCT后谵妄的高发生率与较大的年龄、微血管负荷和调节强度相关。hct前考虑微血管负荷和其他神经成像生物标志物的风险可能是有必要的。
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引用次数: 0
Guidelines for Cord Blood Unit Selection 脐带血单位选择指南
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.07.030
Ioannis Politikos , Eric Davis , Melissa Nhaissi , John E. Wagner , Claudio G. Brunstein , Sandra Cohen , Elizabeth J. Shpall , Filippo Milano , Andromachi Scaradavou , Juliet N. Barker , American Society for Transplantation and Cellular Therapy Cord Blood Special Interest Group

Optimal cord blood (CB) unit selection is critical to maximize the likelihood of successful engraftment and survival after CB transplantation (CBT). However, unit selection can be complex because multiple characteristics must be considered including unit cell dose, donor-recipient human leukocyte antigen (HLA) match, and unit quality. This review provides evidence-based and experience-based comprehensive guidelines for CB unit selection. Topics addressed include the use of both the TNC and the CD34+ cell dose, as well as the CD34+ cell to TNC content ratio to evaluate unit progenitor cell content and engraftment potential, the acceptable TNC and CD34+ cell dose criteria that define an adequate single-unit graft, and the indication and acceptable cell dose criteria for double-unit grafts. The acceptable criteria for 6-loci (HLA-A, -B antigen, -DRB1 allele) and 8-allele (HLA-A, -B, -C, -DRB1) donor-recipient HLA match, the evaluation of patients with donor-specific HLA antibodies, and the multiple determinants of unit quality are also reviewed in detail. Finally, a practical step-by-step guide to CB searches and the principles that guide ultimate graft selection are outlined.

最佳脐带血(CB)单位选择是最大限度地提高脐带血移植(CBT)成功植入和存活的可能性的关键。然而,单位选择可能很复杂,因为必须考虑多种特征,包括单位细胞剂量、供体-受体人类白细胞抗原(HLA)匹配和单位质量。本综述为CB单元的选择提供了基于证据和经验的综合指南。讨论的主题包括TNC和CD34+细胞剂量的使用,以及CD34+细胞与TNC含量的比值来评估单位祖细胞含量和移植潜力,定义适当的单单位移植的可接受TNC和CD34+细胞剂量标准,以及双单位移植的适应症和可接受细胞剂量标准。对6位点(HLA- a, -B抗原,-DRB1等位基因)和8位点(HLA- a, -B, -C, -DRB1)供体-受体HLA匹配的可接受标准,供体特异性HLA抗体患者的评估,以及单位质量的多个决定因素也进行了详细综述。最后,对CB搜索和指导最终移植物选择的原则进行了概述。
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引用次数: 38
Clinical-Grade Expanded Regulatory T Cells Are Enriched with Highly Suppressive Cells Producing IL-10, Granzyme B, and IL-35 临床级扩增调节性T细胞富含产生IL-10、颗粒酶B和IL-35的高抑制性细胞
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.034
Francesca Ulbar , Ida Villanova , Raffaella Giancola , Stefano Baldoni , Francesco Guardalupi , Bianca Fabi , Paola Olioso , Anita Capone , Rosaria Sola , Sara Ciardelli , Beatrice Del Papa , Antonello Brattelli , Ilda Ricciardi , Stefano Taricani , Giulia Sabbatinelli , Ornella Iuliani , Cecilia Passeri , Paolo Sportoletti , Stella Santarone , Antonio Pierini , Mauro Di Ianni

In the setting of T cell-depleted, full-haplotype mismatched transplantation, adoptive immunotherapy with regulatory T cells (Tregs) and conventional T cells (Tcons) can prevent graft-versus-host disease (GVHD) and improve post-transplantation immunologic reconstitution and is associated with a powerful graft-versus-leukemia effect. To improve the purity and the quantity of the infused Tregs, good manufacturing practices (GMP)-compatible expansion protocols are needed. Here we expanded Tregs using an automated, clinical-grade protocol. Cells were extensively characterized in vitro, and their efficiency was tested in vivo in a mouse model. Tregs were selected by CliniMacs (CD4+CD25+, 94.5 ± 6.3%; FoxP3+, 63.7 ± 11.5%; CD127+, 20 ± 3%; suppressive activity, 60 ± 7%), and an aliquot of 100 × 106 was expanded for 14 days using the CliniMACS Prodigy System, obtaining 684 ± 279 × 106 cells (CD4+CD25+, 99.6 ± 0.2%; FoxP3+, 82 ± 8%; CD127+, 1.1 ± 0.8%; suppressive activity, 75 ± 12%). CD39 and CTLA4 expression levels increased from 22.4 ± 12% to 58.1 ± 13.3% (P < .05) and from 20.4 ± 6.7% to 85.4 ± 9.8% (P < .01), respectively. TIM3 levels increased from .4 ± .05% to 29 ± 16% (P < .05). Memory Tregs were the prevalent population, whereas naive Tregs almost disappeared at the end of the culture. mRNA analysis displayed significant increases in CD39, IL-10, granzyme B, and IL-35 levels at the end of culture period (P < .05). Conversely, IFNγ expression decreased significantly by day +14. Expanded Tregs were sorted according to TIM3, CD39, and CD62L expression levels (purity >95%). When sorted populations were analyzed, TIM3+ cells showed significant increases in IL-10 and granzyme B (P < .01) .When expanded Tregs were infused in an NSG murine model, mice that received Tcons only died of GVHD, whereas mice that received both Tcons and Tregs survived without GVHD. GMP grade expanded cells that display phenotypic and functional Treg characteristics can be obtained using a fully automated system. Treg suppression is mediated by multiple overlapping mechanisms (eg, CTLA-4, CD39, IL-10, IL-35, TGF-β, granzyme B). TIM3+ cells emerge as a potentially highly suppressive population.

© 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

在T细胞衰竭、全单倍型错配移植的情况下,调节性T细胞(Tregs)和常规T细胞(Tcons)的过继免疫治疗可以预防移植物抗宿主病(GVHD)和改善移植后免疫重建,并与强大的移植物抗白血病效应相关。为了提高注射Tregs的纯度和数量,需要符合良好生产规范(GMP)的扩增协议。在这里,我们使用自动化的临床级方案扩展Tregs。在体外对细胞进行了广泛的表征,并在小鼠模型中对其效率进行了体内测试。CliniMacs筛选treg (CD4+CD25+, 94.5±6.3%;FoxP3+, 63.7±11.5%;Cd127 +, 20±3%;使用CliniMACS Prodigy系统扩增14天,获得684±279 × 106个细胞(CD4+CD25+, 99.6±0.2%;FoxP3+, 82±8%;Cd127 +, 1.1±0.8%;抑制活性,75±12%)。CD39和CTLA4的表达水平从22.4±12%增加到58.1±13.3% (P <0.05),从20.4±6.7%上升到85.4±9.8% (P <. 01),分别。TIM3水平从0.4±0.05%上升至29±16% (P <. 05)。记忆型treg是普遍存在的群体,而幼稚型treg在培养结束时几乎消失了。mRNA分析显示CD39、IL-10、颗粒酶B和IL-35水平在培养期结束时显著升高(P <. 05)。相反,IFNγ的表达在第14天显著下降。扩增treg根据TIM3、CD39和CD62L表达水平进行分类(纯度>95%)。对分选群体进行分析时,TIM3+细胞IL-10和颗粒酶B显著升高(P <在NSG小鼠模型中注入扩增的Tregs,接受Tcons的小鼠仅死于GVHD,而同时接受Tcons和Tregs的小鼠则存活,无GVHD。使用全自动系统可以获得显示表型和功能Treg特征的GMP级扩增细胞。Treg抑制是由多种重叠机制介导的(如CTLA-4、CD39、IL-10、IL-35、TGF-β、颗粒酶B)。TIM3+细胞是一种潜在的高抑制群体。©2020美国移植和细胞治疗学会。Elsevier Inc.出版。
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引用次数: 8
Outcomes with Autologous or Allogeneic Stem Cell Transplantation in Patients with Plasma Cell Leukemia in the Era of Novel Agents 在新药物时代,自体或异体干细胞移植治疗浆细胞白血病的结果
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.035
Christopher Lemieux, Laura J. Johnston, Robert Lowsky, Lori S. Muffly, Juliana K. Craig, Parveen Shiraz, Andrew Rezvani, Matthew J. Frank, Wen-Kai Weng, Everett Meyer, Judith Shizuru, Sally Arai, Robert Negrin, David B. Miklos, Surbhi Sidana

Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (auto) or allogeneic (allo) stem cell transplantation (SCT) is not clear, given the lack of clinical trial-based evidence. This single-center retrospective study describes the outcomes of 16 patients with PCL (n = 14 with primary PCL) who underwent either autoSCT (n = 9) or alloSCT (n = 7) for PCL in the era of novel agents, between 2007 and 2019. The median age of the cohort was 58 years. High-risk cytogenetics were found in 50% of the patients. All patients received a proteasome inhibitor and/or immunomodulatory drug-based regimen before transplantation. At the time of transplantation, 10 patients (62%) obtained at least a very good partial response (VGPR). The response after autoSCT (3 months) was at least a VGPR in 6 patients (67%; complete response [CR] in 5). All patients undergoing alloSCT achieved a CR at 3 months. Maintenance therapy was provided to 5 patients (56%) after autoSCT. The median progression-free survival after transplantation was 6 months in the autoSCT group, compared with 18 months in the alloSCT group (P = .09), and median overall survival (OS) after transplantation in the 2 groups was 19 months and 40 months, respectively (P = .41). The median OS from diagnosis was 27 months and 49 months, respectively (P = .50). Of the 11 deaths, 10 patients (91%) died of relapsed disease. AlloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, in agreement with recent reports, and relapse remains the primary cause of death in these patients.

浆细胞白血病(PCL)是一种罕见的侵袭性浆细胞疾病。由于缺乏基于临床试验的证据,最佳治疗方法,包括是否进行自体(auto)或同种异体(allo)干细胞移植(SCT)尚不清楚。这项单中心回顾性研究描述了在2007年至2019年新药物时代,16名PCL患者(n = 14名原发性PCL患者)接受了自体sct (n = 9)或同种异体sct (n = 7)治疗PCL的结果。该队列的中位年龄为58岁。50%的患者存在高危细胞遗传学。所有患者在移植前均接受蛋白酶体抑制剂和/或免疫调节药物治疗。移植时,10例患者(62%)获得了至少非常好的部分缓解(VGPR)。autoSCT(3个月)后至少有6例患者(67%;所有接受同种异体细胞移植的患者在3个月时均达到完全缓解(CR)。5例患者(56%)在autoSCT后接受维持治疗。autoSCT组移植后的中位无进展生存期为6个月,而alloSCT组为18个月(P = 0.09),两组移植后的中位总生存期(OS)分别为19个月和40个月(P = 0.41)。诊断后的中位OS分别为27个月和49个月(P = 0.50)。在11例死亡病例中,10例(91%)死于疾病复发。与最近的报道一致,在PCL中,没有观察到同种异体细胞移植比自体细胞移植提供任何显著的生存优势,复发仍然是这些患者死亡的主要原因。
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引用次数: 7
Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis: Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model 预测骨髓纤维化患者同种异体造血细胞移植后的生存:骨髓纤维化移植评分系统(MTSS)的性能和新预后模型的发展
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.07.022
Juan-Carlos Hernández-Boluda , Arturo Pereira , Alberto Alvarez-Larran , Ana-Africa Martín , Ana Benzaquen , Lourdes Aguirre , Elvira Mora , Pedro González , Jorge Mora , Nieves Dorado , Antonia Sampol , Valentín García-Gutiérrez , Oriana López-Godino , María-Laura Fox , Juan Luis Reguera , Manuel Pérez-Encinas , María-Jesús Pascual , Blanca Xicoy , Rocío Parody , Leslie González-Pinedo , José-Luis Piñana

Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P < .001).

We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P < .001).

In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF.

准确的预后工具对于评估骨髓纤维化(MF)患者异体造血细胞移植(alloc - hct)的风险/收益比至关重要。我们的目的是评估骨髓纤维化移植评分系统(MTSS)的性能,并在197名接受同种异体hct治疗的MF患者的多中心系列研究中确定生存的危险因素。中位随访3.1年后,47%的患者死亡,估计5年生存率为51%。预计5年非复发死亡率和复发率分别为30%和20%。与死亡率增加独立相关的因素是造血细胞移植特异性合并症指数(HCT-CI)≥3和接受hla不匹配的非亲属供体或脐带血移植,而移植后环磷酰胺(PT-Cy)与生存率提高相关。供体类型是MTSS模型中唯一具有独立生存预后价值的参数。根据MTSS,低、中、高、高危组的3年生存率分别为62%、66%、37%和17%。通过将低、中危组以及高、高危组汇总在一起,我们确定了两类:标准危组和高危组(占该系列的25%)。标准风险组的3年生存率为62%,高风险组为25% (P <措施)。我们根据三个独立的生存风险因素(供体类型、HCT-CI和PT-Cy)得出了一个风险评分。低、中、高风险组相应的5年生存率分别为79%、55%和32% (P <措施)。总之,在我们的研究中,MTSS模型未能清晰地描述4个预后组,但可能仍然有助于识别预后不良的患者亚群。我们为MF患者移植前的风险/获益考虑提供了一个简单的预后评分系统。
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引用次数: 12
期刊
Biology of Blood and Marrow Transplantation
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