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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
Individuals, Boundaries, and Graft-versus-Host Disease 个体、边界和移植物抗宿主病
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.09.001
H. Joachim Deeg

Hematopoietic cell transplantation generates new individuals, transplant chimeras, composed of 2 genetic partners—the patient and donor-derived cells—no longer restricted by their original genomes. Interactions of donor-derived and recipient cells occur prominently at the boundary of the recipient with a third partner, the microbiome, in particular skin and intestinal tract, leading to disruption of microbiome homeostasis. These interactions of donor and patient cells at the boundary set the stage for the development of graft-versus-host disease, an expression of the defense of individuality by recipient and donor. Establishment of tolerance and return of homeostasis at the boundary will allow for the survival of the new integrated, physiologic individual.

造血细胞移植产生新的个体,移植嵌合体,由2个基因伴侣组成-患者和供体来源的细胞-不再受其原始基因组的限制。供体来源细胞和受体细胞的相互作用主要发生在受体与第三个伙伴,微生物组,特别是皮肤和肠道的边界,导致微生物组稳态的破坏。这些供体和患者细胞在边界的相互作用为移植物抗宿主病的发展奠定了基础,这是受体和供体对个体防御的一种表达。在边界处建立耐受性和恢复体内平衡将允许新的完整的生理个体的生存。
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引用次数: 1
Health-Related Quality-of-Life Comparison of Adult Related and Unrelated HSC Donors: An RDSafe Study 成人相关和非相关HSC供体的健康相关生活质量比较:一项RDSafe研究
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.016
Galen E. Switzer , Jessica G. Bruce , Deidre M. Kiefer , Hati Kobusingye , Kaleab Z. Abebe , Rebecca Drexler , RaeAnne M. Besser , Dennis L. Confer , Mary M. Horowitz , Roberta J. King , Bronwen E. Shaw , Marcie Riches , Brandon Hayes-Lattin , Michael Linenberger , Brian Bolwell , Scott D. Rowley , Mark R. Litzow , Michael A. Pulsipher

Multiple investigations have documented the health-related quality-of-life (HRQoL) and donation-related experiences of unrelated donors (URDs), but similar investigations of the related donor (RD) experience have been less common. The central goal of this study was to longitudinally examine and compare HRQoL of RD and URD hematopoietic stem cell (HSC) donors from predonation through 1 year postdonation. This prospective investigation included adult HSC donors ages 18 to 60 years who donated bone marrow or peripheral blood stem cells at one of 48 geographically diverse US transplant/donor centers and completed HRQoL interviews at predonation and 4 weeks and 1 year postdonation. At predonation, related donors were less ambivalent about donation (t = –3.30; P = .001), more satisfied with their decision to donate (t = 2.65; P = .009), and more likely to define themselves as donors (t = 2.94; P = .004) than were URDs. However, related donors were more concerned about the use of needles (odds ratio [OR] = 2.19; P = .012), about who would pay for the procedure (OR = 2.80; P = .011), and the possibility that they would feel responsible if the transplant failed (t = 2.31; P = .022). Shortly postdonation, related donors were more likely to report donation-related pain (t = 2.50; P = .013) and lightheadedness (OR = 3.63; P = .028). At 1 year postdonation, related donors were less likely to be fully recovered from donation (OR = 0.10; P = .010) and more likely to report a longer recovery period following donation (t = 2.57; P = .011), although this latter finding was primarily due to the percentage of related versus unrelated donors not fully recovered at 1 year postdonation (10% versus 1%). Taken together, these findings suggest that current related donor management practices may be sufficient in preparing related donors for the psychological aspects of donation but that there may be more to do in terms of calibrating the description of donation-related experiences and recovery time to the related donor group (i.e., descriptions of donation experiences based on unrelated donation may not provide best estimates of experience for this group).

多项调查记录了非亲属献血者(URDs)的健康相关生活质量(HRQoL)和捐赠相关经历,但对相关献血者(RD)经历的类似调查却不太常见。本研究的中心目标是纵向检查和比较RD和URD造血干细胞(HSC)供者从捐献前到捐献后1年的HRQoL。这项前瞻性调查包括年龄在18至60岁的成人HSC捐赠者,他们在美国48个地理位置不同的移植/捐赠中心之一捐赠骨髓或外周血干细胞,并在捐赠前、捐赠后4周和1年完成HRQoL访谈。在捐赠前,相关献血者对捐赠的矛盾心理较少(t = -3.30;P = .001),对捐赠决定更满意(t = 2.65;P = 0.009),更有可能将自己定义为捐赠者(t = 2.94;P = .004)。然而,相关献血者更关心针头的使用(优势比[OR] = 2.19;P = .012),关于谁将支付手术费用(OR = 2.80;P = 0.011),如果移植失败,他们会感到有责任的可能性(t = 2.31;p = .022)。在捐赠后不久,相关的献血者更有可能报告捐赠相关的疼痛(t = 2.50;P = 0.013)和头晕(OR = 3.63;p = .028)。在捐赠后1年,相关献血者不太可能从捐赠中完全恢复(OR = 0.10;P = 0.010),更有可能报告捐赠后的恢复期较长(t = 2.57;P = 0.011),尽管后一项发现主要是由于亲属和非亲属捐赠者在捐赠后1年未完全康复的百分比(10%对1%)。综上所述,这些发现表明,目前的相关捐赠者管理实践可能足以使相关捐赠者做好捐赠心理方面的准备,但在校准捐赠相关经历的描述和相关捐赠群体的恢复时间方面可能还有更多工作要做(即,基于不相关捐赠的捐赠经历描述可能无法为该群体提供最佳的经验估计)。
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引用次数: 5
Incidence and Outcome of Late Relapse after Allogeneic Stem Cell Transplantation for Myelofibrosis 同种异体干细胞移植治疗骨髓纤维化后晚期复发的发生率和结果
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.09.006
Isik Kaygusuz Atagunduz , Maximilian Christopeit , Francis Ayuk , Gaby Zeck , Christine Wolschke , Nicolaus Kröger

In this cross-sectional study, we retrospectively evaluated the files of 227 patients with myelofibrosis who underwent transplantation between 1994 and 2015 for relapse later than 5 years after allogeneic stem cell transplantation (SCT). A total of 94 patients who were alive and in remission at 5 years were identified with follow-up of at least 5 years (median, 9.15 years) after SCT. Thirteen patients (14%) experienced late molecular (n = 6) or hematologic (n = 7) relapse at a median of 7.1 years while 81 patients did not experience relapse. Relapse patients received either donor lymphocyte infusion (DLI) (n = 7) and/or second transplantation (n = 4). Of those, 72.7% achieved again full donor cell chimerism and molecular remission, and after a median follow-up of 45 months, the 3-year overall survival rates for patients with or without relapse were 90.9% (95% confidence interval [CI], 77% to 100%) and 98.8% (95% CI, 96% to 100%), respectively (P = .13). We conclude that late relapse occurs in about 14% of the patients and the majority can be successfully salvaged with DLI and/or second allograft. All patients with molecular relapse are alive and support the long-time molecular monitoring in myelofibrosis patients after allogeneic SCT.

在这项横断面研究中,我们回顾性评估了1994年至2015年间接受移植的227例骨髓纤维化患者在同种异体干细胞移植(SCT)后5年内复发的档案。在SCT后随访至少5年(中位9.15年),共有94名患者存活并在5年缓解。13名患者(14%)经历了晚期分子(n = 6)或血液学(n = 7)复发,中位时间为7.1年,而81名患者没有复发。复发患者接受供体淋巴细胞输注(DLI) (n = 7)和/或第二次移植(n = 4)。其中,72.7%再次实现供体细胞完全嵌合和分子缓解,中位随访45个月后,复发或无复发患者的3年总生存率分别为90.9%(95%置信区间[CI], 77%至100%)和98.8% (95% CI, 96%至100%)(P = 0.13)。我们得出结论,晚期复发发生在大约14%的患者中,大多数患者可以通过DLI和/或第二次同种异体移植成功挽救。所有分子复发的患者都存活,支持同种异体SCT后骨髓纤维化患者的长期分子监测。
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引用次数: 2
Posterior Reversible Encephalopathy Syndrome after Allogeneic Stem Cell Transplantation in Pediatric Patients with Fanconi Anemia, a Prospective Study 儿童范可尼贫血患者异体干细胞移植后后部可逆性脑病综合征的前瞻性研究
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.021
Maryam Behfar , Mohammad Babaei , Amir Reza Radmard , Soheil Kooraki , Hamid Farajifard , Parisa Naji , Sahar Taebi , Amir Ali Hamidieh

Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurologic complications following hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the incidence, clinical, and imaging features of PRES in pediatric patients with Fanconi anemia (FA) following HSCT. This prospective study included all post-HSCT patients with underlying FA disease between 2014 and 2017. Brain computed tomography scan and magnetic resonance imaging (MRI) were performed in all individuals who developed neurologic symptoms. PRES was diagnosed based on clinic-radiological evidence. Follow-up MRI was performed in all patients with PRES within two months. Forty-one patients with FA (28 males; mean age, 8.19 ± 3.25 years) were enrolled. Out of 15 patients with acute neurologic symptoms, PRES was diagnosed in 9 individuals (21.95% of the total cohort). The occurrence of PRES was significantly higher in patients who had a donor with a 1-locus mismatch (P= .02). Donor relation, stem cell source, and graft-versus-host disease grade did not have any significant association with the development of PRES. MRI showed asymmetric vasogenic edema in 5 patients, an overt infarct in 1 patient, and foci of microhemorrhages in 3 patients, 1 of whom developed a hemorrhagic infarct. This patient died shortly, and persistent microhemorrhages were noted in the other 2 patients. Our findings demonstrate a greater risk of developing PRES after HSCT in patients with FA compared with those with other diseases (21.95% versus 1% to 10%), and in contrast to its term, it might be irreversible and has adverse effects on HSCT outcomes. The increased vascular and endothelial fragility in FA may contribute to the higher frequency of PRES in these individuals.

后可逆性脑病综合征(PRES)是造血干细胞移植(HSCT)后最常见的神经系统并发症之一。我们的目的是评估HSCT后儿童范可尼贫血(FA)患者PRES的发生率、临床和影像学特征。这项前瞻性研究纳入了2014年至2017年间所有患有潜在FA疾病的hsct后患者。对所有出现神经系统症状的个体进行脑计算机断层扫描和磁共振成像(MRI)。PRES是根据临床放射学证据诊断的。所有PRES患者均在2个月内随访MRI。FA 41例(男性28例;平均年龄(8.19±3.25岁)。在15例有急性神经系统症状的患者中,有9例(占总队列的21.95%)被诊断为PRES。1位点不匹配的供体患者的PRES发生率显著高于1位点不匹配的供体(P= 0.02)。供体关系、干细胞来源和移植物抗宿主病分级与PRES的发生无显著相关性。MRI显示5例患者血管源性水肿不对称,1例患者有明显梗死,3例患者有微出血灶,其中1例发生出血性梗死。该患者很快死亡,另外2例患者出现持续性微出血。我们的研究结果表明,与其他疾病患者相比,FA患者在HSCT后发生PRES的风险更高(21.95%比1% - 10%),并且与其期限相反,它可能是不可逆的,并且对HSCT结果有不利影响。FA患者血管和内皮易碎性的增加可能导致这些患者发生PRES的频率更高。
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引用次数: 5
Outcome of Allogeneic Hematopoietic Cell Transplantation after Venetoclax and Hypomethylating Agent Therapy for Acute Myelogenous Leukemia 异基因造血细胞移植治疗急性骨髓性白血病的效果
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.027
Karamjeet S. Sandhu, Sanjeet Dadwal, Dongyun Yang, Matthew Mei, Joycelynne Palmer, Amandeep Salhotra, Monzr Al Malki, Ahmed Aribi, Haris Ali, Samer Khaled, Stephen J. Forman, David Snyder, Ryotaro Nakamura, Anthony S. Stein, Guido Marcucci, Ibrahim Aldoss, Vinod Pullarkat

The combination of hypomethylating agents with the selective Bcl-2 inhibitor venetoclax (HMA-VEN) has emerged as a highly active regimen in patients with acute myelogenous leukemia (AML) in both the upfront and relapsed/refractory (r/r) settings. We report our early experience with a cohort of patients who were able to proceed to allogeneic hematopoietic cell transplantation (alloHCT) after HMA-VEN therapy. Thirty-two patients with AML (19 r/r and 13 de novo) with a median age of 62 years underwent alloHCT after HMA-VEN therapy. Twenty-two (68.8%) were in complete remission (CR)/CR with incomplete count recovery at time of HCT. With a median follow up of 14.4 months, the 1-year overall survival (OS) was 62.5%, and disease-free survival was 43.8%. The 1-year nonrelapse mortality rate was 18.8%, and the cumulative incidence of relapse was 37.5%. Among patients who underwent alloHCT in CR, the 1-year OS was 77.3%, and the cumulative incidence of nonrelapse mortality was 9.1%. The cumulative incidence of grade II-IV acute graft-versus-host disease was 43.8%. We conclude that alloHCT after HMA-VEN is therapy associated with favorable allogeneic HCT outcomes in newly diagnosed older patients with AML, as well as those with r/r AML.

低甲基化药物联合选择性Bcl-2抑制剂venetoclax (HMA-VEN)已成为急性髓性白血病(AML)患者在前期和复发/难治性(r/r)患者中的一种高活性方案。我们报告了一组患者在HMA-VEN治疗后能够进行同种异体造血细胞移植(alloHCT)的早期经验。32例AML患者(19例复发/复发,13例新生)在HMA-VEN治疗后接受了同种异体hct治疗,中位年龄为62岁。22例(68.8%)在HCT时完全缓解(CR)/计数恢复不完全的CR。中位随访14.4个月,1年总生存率(OS)为62.5%,无病生存率为43.8%。1年未复发死亡率为18.8%,累计复发率为37.5%。在CR中接受同种异体hct的患者中,1年总生存率为77.3%,累计非复发死亡率为9.1%。II-IV级急性移植物抗宿主病的累积发病率为43.8%。我们得出结论,HMA-VEN后的同种异体HCT治疗与新诊断的老年AML患者以及r/r AML患者的同种异体HCT预后相关。
{"title":"Outcome of Allogeneic Hematopoietic Cell Transplantation after Venetoclax and Hypomethylating Agent Therapy for Acute Myelogenous Leukemia","authors":"Karamjeet S. Sandhu,&nbsp;Sanjeet Dadwal,&nbsp;Dongyun Yang,&nbsp;Matthew Mei,&nbsp;Joycelynne Palmer,&nbsp;Amandeep Salhotra,&nbsp;Monzr Al Malki,&nbsp;Ahmed Aribi,&nbsp;Haris Ali,&nbsp;Samer Khaled,&nbsp;Stephen J. Forman,&nbsp;David Snyder,&nbsp;Ryotaro Nakamura,&nbsp;Anthony S. Stein,&nbsp;Guido Marcucci,&nbsp;Ibrahim Aldoss,&nbsp;Vinod Pullarkat","doi":"10.1016/j.bbmt.2020.08.027","DOIUrl":"10.1016/j.bbmt.2020.08.027","url":null,"abstract":"<div><p>The combination of hypomethylating agents with the selective Bcl-2 inhibitor venetoclax (HMA-VEN) has emerged as a highly active regimen in patients with acute myelogenous leukemia (AML) in both the upfront and relapsed/refractory (r/r) settings. We report our early experience with a cohort of patients who were able to proceed to allogeneic hematopoietic cell transplantation (alloHCT) after HMA-VEN therapy. Thirty-two patients with AML (19 r/r and 13 de novo) with a median age of 62 years underwent alloHCT after HMA-VEN therapy. Twenty-two (68.8%) were in complete remission (CR)/CR with incomplete count recovery at time of HCT. With a median follow up of 14.4 months, the 1-year overall survival (OS) was 62.5%, and disease-free survival was 43.8%. The 1-year nonrelapse mortality rate was 18.8%, and the cumulative incidence of relapse was 37.5%. Among patients who underwent alloHCT in CR, the 1-year OS was 77.3%, and the cumulative incidence of nonrelapse mortality was 9.1%. The cumulative incidence of grade II-IV acute graft-versus-host disease was 43.8%. We conclude that alloHCT after HMA-VEN is therapy associated with favorable allogeneic HCT outcomes in newly diagnosed older patients with AML, as well as those with r/r AML.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":"26 12","pages":"Pages e322-e327"},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38327387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 32
Real-World Issues and Potential Solutions in Hematopoietic Cell Transplantation during the COVID-19 Pandemic: Perspectives from the Worldwide Network for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research Health Services and International Studies Committee COVID-19大流行期间造血细胞移植的现实问题和潜在解决方案:来自全球血液和骨髓移植网络和国际血液和骨髓移植研究中心卫生服务和国际研究委员会的观点
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.07.021
Ghada Algwaiz , Mahmoud Aljurf , Mickey Koh , Mary M. Horowitz , Per Ljungman , Daniel Weisdorf , Wael Saber , Yoshihisa Kodera , Jeff Szer , Dunia Jawdat , William A. Wood , Ruta Brazauskas , Leslie Lehmann , Marcelo C. Pasquini , Adriana Seber , Pei Hua Lu , Yoshiko Atsuta , Marcie Riches , Miguel-Angel Perales , Nina Worel , Shahrukh K. Hashmi

The current COVID-19 pandemic, caused by SARS-CoV-2, has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. Realizing the challenges as a result of this pandemic affecting the daily practice of the HCT centers and the recognition of the variability in practice worldwide, the Worldwide Network for Blood and Marrow Transplantation (WBMT) and the Center for International Blood and Marrow Transplant Research's (CIBMTR) Health Services and International Studies Committee have jointly produced an expert opinion statement as a general guide to deal with certain aspects of HCT, including diagnostics for SARS-CoV-2 in HCT recipient, pre- and post-HCT management, donor issues, medical tourism, and facilities management. During these crucial times, which may last for months or years, the HCT community must reorganize to proceed with transplantation activity in those patients who urgently require it, albeit with extreme caution. This shared knowledge may be of value to the HCT community in the absence of high-quality evidence-based medicine.

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

当前由SARS-CoV-2引起的COVID-19大流行,对发达国家和发展中国家造血细胞移植(HCT)的许多方面都产生了影响。认识到此次大流行对HCT中心日常工作的影响所带来的挑战,以及认识到世界范围内实践的差异,世界血液和骨髓移植网络(WBMT)和国际血液和骨髓移植研究中心(CIBMTR)卫生服务和国际研究委员会联合编写了一份专家意见声明,作为处理HCT某些方面的一般指南。包括HCT接受者的SARS-CoV-2诊断、HCT前后的管理、捐赠者问题、医疗旅游和设施管理。在这些可能持续数月或数年的关键时期,HCT社区必须重新组织,对那些迫切需要移植的患者进行移植活动,尽管要非常谨慎。在缺乏高质量循证医学的情况下,这种共享的知识可能对HCT社区有价值。©2020美国移植和细胞治疗学会。Elsevier Inc.出版。
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引用次数: 40
Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation for Mature T Cell and Natural Killer Cell Neoplasms in the Kyoto Stem Cell Transplantation Group 供体来源对京都干细胞移植组成熟T细胞和自然杀伤细胞肿瘤同种异体造血干细胞移植的影响
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.07.032
Mizuki Watanabe , Junya Kanda , Yasuyuki Arai , Masakatsu Hishizawa , Momoko Nishikori , Takayuki Ishikawa , Kazunori Imada , Yasunori Ueda , Takashi Akasaka , Akihito Yonezawa , Masaharu Nohgawa , Toshiyuki Kitano , Mitsuru Itoh , Tomoharu Takeoka , Toshinori Moriguchi , Kazuhiro Yago , Nobuyoshi Arima , Naoyuki Anzai , Mitsumasa Watanabe , Tadakazu Kondo , Akifumi Takaori-Kondo

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the key strategy to cure patients with mature T and natural killer (NK) cell lymphomas/leukemia, especially those with relapsed/refractory diseases, there is no consensus strategy for donor selection. We retrospectively analyzed the outcomes of allo-HSCT in 111 patients in 15 Japanese institutions as a multi-institutional joint research project. Thirty-nine patients received bone marrow or peripheral blood stem cell transplantation from related donors (rBMT/rPBSCT), 37 received BMT/PBSCT from unrelated donors (uBMT/uPBSCT), and 35 received cord blood transplantation (CBT). Overall survival (OS) and progression-free survival (PFS) at 4 years were 42% and 34%, respectively. The cumulative incidences of relapse and nonrelapse mortality were 43% and 25%. In multivariate analysis, CBT showed comparable OS with rBMT/rPBSCT (rBMT/rPBSCT versus CBT: hazard ratio [HR], 1.63; P = .264) and better OS compared with uBMT/uPBSCT (HR, 2.99; P = .010), with a trend toward a lower relapse rate (rBMT/rPBSCT versus CBT: HR, 2.60; P = .010; uBMT/uPBSCT versus CBT: HR, 2.05; P = .082). This superiority of CBT was more definite in on-disease patients (OS: rBMT/rPBSCT versus CBT: HR, 5.52; P = .021; uBMT/uPBSCT versus CBT: HR, 6.80; P = .007). Better disease control was also strongly associated with better OS and PFS with lower relapse rate. In conclusion, allo-HSCT is beneficial for the survival of patients with mature T and NK cell lymphomas/leukemia if performed in a timely fashion. Since CBT showed favorable survival with a lower relapse risk, it could be a preferred alternative, especially in on-disease patients.

尽管同种异体造血干细胞移植(allogeneic hematopoietic stem cell transplantation, alloo - hsct)是治疗成熟T细胞和自然杀伤细胞(NK)淋巴瘤/白血病的关键策略,尤其是那些复发/难治性疾病的患者,但在供体选择方面尚无共识策略。作为一项多机构联合研究项目,我们回顾性分析了日本15家机构111例患者的同种异体造血干细胞移植结果。39例患者接受了亲属供者的骨髓或外周血干细胞移植(rBMT/rPBSCT), 37例接受了非亲属供者的BMT/PBSCT (uBMT/uPBSCT), 35例接受了脐带血移植(CBT)。4年总生存期(OS)和无进展生存期(PFS)分别为42%和34%。复发和非复发死亡率的累计发生率分别为43%和25%。在多变量分析中,CBT显示出与rBMT/rPBSCT相当的OS (rBMT/rPBSCT vs CBT:风险比[HR], 1.63;P = .264),与uBMT/uPBSCT相比,OS更好(HR, 2.99;P = 0.010),复发率呈较低趋势(rBMT/rPBSCT与CBT: HR, 2.60;p = 0.010;uBMT/uPBSCT与CBT: HR, 2.05;p = .082)。CBT的优势在非疾病患者中更为明确(OS: rBMT/rPBSCT vs CBT: HR, 5.52;p = 0.021;uBMT/uPBSCT与CBT: HR, 6.80;p = .007)。更好的疾病控制也与更好的OS和PFS以及更低的复发率密切相关。总之,如果及时进行同种异体造血干细胞移植,对成熟T细胞和NK细胞淋巴瘤/白血病患者的生存是有益的。由于CBT表现出较好的生存率和较低的复发风险,因此它可能是一种首选的替代方案,特别是在未患病的患者中。
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引用次数: 3
期刊
Biology of Blood and Marrow Transplantation
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