Biology of Blood and Marrow Transplantation最新文献

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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
Biology of Blood and Marrow Transplantation 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
{"title":"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","authors":"Alexandra Gauthier ,&nbsp;Nathalie Bleyzac ,&nbsp;Nathalie Garnier ,&nbsp;Kamila Kebaili ,&nbsp;Philippe Joly ,&nbsp;Marie-Pierre Goutagny ,&nbsp;Isabelle Mollet ,&nbsp;Sylvain Goutelle ,&nbsp;Cécile Renard ,&nbsp;Yves Bertrand","doi":"10.1016/j.bbmt.2020.01.016","DOIUrl":"10.1016/j.bbmt.2020.01.016","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.01.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37601574","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Pre-Hematopoietic Stem Cell Transplantation Lung Computed Tomography as an Alternative to the Pulmonary Function Test during the COVID-19 Pandemic","authors":"Masaharu Tamaki ,&nbsp;Hideki Nakasone ,&nbsp;Tadao Aikawa ,&nbsp;Yuhei Nakamura ,&nbsp;Masakatsu Kawamura ,&nbsp;Shunto Kawamura ,&nbsp;Junko Takeshita ,&nbsp;Nozomu Yoshino ,&nbsp;Yukiko Misaki ,&nbsp;Kazuki Yoshimura ,&nbsp;Shinpei Matsumi ,&nbsp;Ayumi Gomyo ,&nbsp;Aki Tanihara ,&nbsp;Machiko Kusuda ,&nbsp;Yu Akahoshi ,&nbsp;Shun-ichi Kimura ,&nbsp;Shinichi Kako ,&nbsp;Noriko Oyama-Manabe ,&nbsp;Yoshinobu Kanda","doi":"10.1016/j.bbmt.2020.08.025","DOIUrl":"10.1016/j.bbmt.2020.08.025","url":null,"abstract":"<div><p>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%, <em>P</em> = .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; <em>P</em> = .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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38323566","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: 2
Officers and Directors of ASTCT ASTCT的官员和董事
IF 4.3
Biology of Blood and Marrow Transplantation Pub Date : 2020-12-01 DOI: 10.1016/S1083-8791(20)30705-9
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S1083-8791(20)30705-9","DOIUrl":"https://doi.org/10.1016/S1083-8791(20)30705-9","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1083-8791(20)30705-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136816042","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Nonmyeloablative Conditioning Regimen before T Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Hodgkin and Non-Hodgkin Lymphomas","authors":"Catalina Montes de Oca ,&nbsp;Luca Castagna ,&nbsp;Chiara De Philippis ,&nbsp;Stefania Bramanti ,&nbsp;Jean Marc Schiano ,&nbsp;Thomas Pagliardini ,&nbsp;Aude Collignon ,&nbsp;Samia Harbi ,&nbsp;Jacopo Mariotti ,&nbsp;Angela Granata ,&nbsp;Valerio Maisano ,&nbsp;Sabine Furst ,&nbsp;Faezeah Legrand ,&nbsp;Christian Chabannon ,&nbsp;Carmelo Carlo-Stella ,&nbsp;Armando Santoro ,&nbsp;Didier Blaise ,&nbsp;Raynier Devillier","doi":"10.1016/j.bbmt.2020.08.014","DOIUrl":"10.1016/j.bbmt.2020.08.014","url":null,"abstract":"<div><p>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%, <em>P</em> = .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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38296340","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma","authors":"Kathleen Monahan ,&nbsp;Ariel Kleman ,&nbsp;Bicky Thapa ,&nbsp;Aniko Szabo ,&nbsp;Anita D'Souza ,&nbsp;Binod Dhakal ,&nbsp;James H. Jerkins ,&nbsp;Marcelo C. Pasquini ,&nbsp;Mehdi Hamadani ,&nbsp;Parameswaran N. Hari ,&nbsp;Saurabh Chhabra","doi":"10.1016/j.bbmt.2020.08.030","DOIUrl":"10.1016/j.bbmt.2020.08.030","url":null,"abstract":"<div><p>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; <em>P</em> &lt; .001), fewer grade 3-4 infections within 30 days of autoHCT (1.5% versus 8.0%; <em>P</em> = .048), and a lower 30-day rehospitalization rate (6.8% versus 17.9%; <em>P</em> = .04), as confirmed by propensity-weighted analysis. No significant between-group differences were detected in mucositis, organ toxicity, myeloma response, or 100-day mortality.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38372974","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Clinical and Neuroimaging Correlates of Post-Transplant Delirium","authors":"Patrick Smith ,&nbsp;Jillian C. Thompson ,&nbsp;Elena Perea ,&nbsp;Brian Wasserman ,&nbsp;Lauren Bohannon ,&nbsp;Alessandro Racioppi ,&nbsp;Taewoong Choi ,&nbsp;Cristina Gasparetto ,&nbsp;Mitchell E. Horwitz ,&nbsp;Gwynn Long ,&nbsp;Richard Lopez ,&nbsp;David A. Rizzieri ,&nbsp;Stefanie Sarantopoulos ,&nbsp;Keith M. Sullivan ,&nbsp;Nelson J. Chao ,&nbsp;Anthony D. Sung","doi":"10.1016/j.bbmt.2020.09.016","DOIUrl":"10.1016/j.bbmt.2020.09.016","url":null,"abstract":"<div><p>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, <em>P</em> = .002), greater severity of white matter hyperintensities (OR, 1.95 [1.06, 3.57], <em>P</em> = .031), and conditioning intensity (OR, 6.37 [2.20, 18.45], <em>P</em> &lt; .001) but was unrelated to cortical atrophy (<em>P</em> = .777). Delirium was associated with fewer hospital-free days (<em>P</em> = .023) but was not associated with overall survival (hazard ratio, 0.95 [0.56, 1.61], <em>P</em> = .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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.09.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38503565","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: 0
Guidelines for Cord Blood Unit Selection 脐带血单位选择指南
IF 4.3
Biology of Blood and Marrow Transplantation 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
{"title":"Guidelines for Cord Blood Unit Selection","authors":"Ioannis Politikos ,&nbsp;Eric Davis ,&nbsp;Melissa Nhaissi ,&nbsp;John E. Wagner ,&nbsp;Claudio G. Brunstein ,&nbsp;Sandra Cohen ,&nbsp;Elizabeth J. Shpall ,&nbsp;Filippo Milano ,&nbsp;Andromachi Scaradavou ,&nbsp;Juliet N. Barker ,&nbsp;American Society for Transplantation and Cellular Therapy Cord Blood Special Interest Group","doi":"10.1016/j.bbmt.2020.07.030","DOIUrl":"10.1016/j.bbmt.2020.07.030","url":null,"abstract":"<div><p>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<sup>+</sup> cell dose, as well as the CD34<sup>+</sup> cell to TNC content ratio to evaluate unit progenitor cell content and engraftment potential, the acceptable TNC and CD34<sup>+</sup> 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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38212626","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Clinical-Grade Expanded Regulatory T Cells Are Enriched with Highly Suppressive Cells Producing IL-10, Granzyme B, and IL-35","authors":"Francesca Ulbar ,&nbsp;Ida Villanova ,&nbsp;Raffaella Giancola ,&nbsp;Stefano Baldoni ,&nbsp;Francesco Guardalupi ,&nbsp;Bianca Fabi ,&nbsp;Paola Olioso ,&nbsp;Anita Capone ,&nbsp;Rosaria Sola ,&nbsp;Sara Ciardelli ,&nbsp;Beatrice Del Papa ,&nbsp;Antonello Brattelli ,&nbsp;Ilda Ricciardi ,&nbsp;Stefano Taricani ,&nbsp;Giulia Sabbatinelli ,&nbsp;Ornella Iuliani ,&nbsp;Cecilia Passeri ,&nbsp;Paolo Sportoletti ,&nbsp;Stella Santarone ,&nbsp;Antonio Pierini ,&nbsp;Mauro Di Ianni","doi":"10.1016/j.bbmt.2020.08.034","DOIUrl":"10.1016/j.bbmt.2020.08.034","url":null,"abstract":"<div><p>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<sup>+</sup>CD25<sup>+</sup>, 94.5 ± 6.3%; FoxP3<sup>+</sup>, 63.7 ± 11.5%; CD127<sup>+</sup>, 20 ± 3%; suppressive activity, 60 ± 7%), and an aliquot of 100 × 10<sup>6</sup> was expanded for 14 days using the CliniMACS Prodigy System, obtaining 684 ± 279 × 10<sup>6</sup> cells (CD4<sup>+</sup>CD25<sup>+</sup>, 99.6 ± 0.2%; FoxP3<sup>+</sup>, 82 ± 8%; CD127<sup>+</sup>, 1.1 ± 0.8%; suppressive activity, 75 ± 12%). CD39 and CTLA4 expression levels increased from 22.4 ± 12% to 58.1 ± 13.3% (<em>P</em> &lt; .05) and from 20.4 ± 6.7% to 85.4 ± 9.8% (<em>P</em> &lt; .01), respectively. TIM3 levels increased from .4 ± .05% to 29 ± 16% (<em>P</em> &lt; .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 (<em>P</em> &lt; .05). Conversely, IFNγ expression decreased significantly by day +14. Expanded Tregs were sorted according to TIM3, CD39, and CD62L expression levels (purity &gt;95%). When sorted populations were analyzed, TIM3<sup>+</sup> cells showed significant increases in IL-10 and granzyme B (<em>P</em> &lt; .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<sup>+</sup> cells emerge as a potentially highly suppressive population.</p><p>© 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38406253","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Outcomes with Autologous or Allogeneic Stem Cell Transplantation in Patients with Plasma Cell Leukemia in the Era of Novel Agents","authors":"Christopher Lemieux,&nbsp;Laura J. Johnston,&nbsp;Robert Lowsky,&nbsp;Lori S. Muffly,&nbsp;Juliana K. Craig,&nbsp;Parveen Shiraz,&nbsp;Andrew Rezvani,&nbsp;Matthew J. Frank,&nbsp;Wen-Kai Weng,&nbsp;Everett Meyer,&nbsp;Judith Shizuru,&nbsp;Sally Arai,&nbsp;Robert Negrin,&nbsp;David B. Miklos,&nbsp;Surbhi Sidana","doi":"10.1016/j.bbmt.2020.08.035","DOIUrl":"10.1016/j.bbmt.2020.08.035","url":null,"abstract":"<div><p>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 (<em>P</em> = .09), and median overall survival (OS) after transplantation in the 2 groups was 19 months and 40 months, respectively (<em>P</em> = .41). The median OS from diagnosis was 27 months and 49 months, respectively (<em>P</em> = .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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38406255","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: 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
Biology of Blood and Marrow Transplantation 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
{"title":"Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis: Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model","authors":"Juan-Carlos Hernández-Boluda ,&nbsp;Arturo Pereira ,&nbsp;Alberto Alvarez-Larran ,&nbsp;Ana-Africa Martín ,&nbsp;Ana Benzaquen ,&nbsp;Lourdes Aguirre ,&nbsp;Elvira Mora ,&nbsp;Pedro González ,&nbsp;Jorge Mora ,&nbsp;Nieves Dorado ,&nbsp;Antonia Sampol ,&nbsp;Valentín García-Gutiérrez ,&nbsp;Oriana López-Godino ,&nbsp;María-Laura Fox ,&nbsp;Juan Luis Reguera ,&nbsp;Manuel Pérez-Encinas ,&nbsp;María-Jesús Pascual ,&nbsp;Blanca Xicoy ,&nbsp;Rocío Parody ,&nbsp;Leslie González-Pinedo ,&nbsp;José-Luis Piñana","doi":"10.1016/j.bbmt.2020.07.022","DOIUrl":"10.1016/j.bbmt.2020.07.022","url":null,"abstract":"<div><p>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 (<em>P</em> &lt; .001).</p><p>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 (<em>P</em> &lt; .001).</p><p>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.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38205685","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: 12
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