Pooja Khandelwal , Vijaya Chaturvedi , Erika Owsley , Yvonne A. Efebera , Hannah Choe , Matthew Bostic , Prashanti Kumchala , Girish Rajgolikar , Parvathi Ranganathan , Ramiro Garzon , Kelly Lake , Bridget Litts , Alexandra Duell , Patrick Elder , Stella M. Davies , Adam Lane , Michael B. Jordan , Sumithra Vasu , Steven Devine , Rebecca A. Marsh
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If CD38 bright CD8+ TEM ≥ 30 cells/µL, Epstein-Barr virus and cytomegalovirus specificity was determined by tetramer staining, granzyme B content was assessed, Ki-67 staining performed to assess T-cell proliferation. Cells were incubated with alemtuzumab, daratumumab and cyclophosphamide <em>in vitro</em> to determine susceptibility to depletion.</p></div><div><h3>Results</h3><p>Of the 182 enrolled patients, 83 (45.6%) developed acute GVHD by day+100 but 171 patients were evaluable (acute GVHD <em>n</em> = 77 and no GVHD <em>n</em> = 94). There was no difference in the maximum absolute CD38 bright CD8+TEM cells prior to clinical symptoms and also after CMV and EBV tetramer positive patients were excluded from both cohorts. Ki-67 or Granzyme B expression in patients were comparable between patients with and without acute GVHD. 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Efebera , Hannah Choe , Matthew Bostic , Prashanti Kumchala , Girish Rajgolikar , Parvathi Ranganathan , Ramiro Garzon , Kelly Lake , Bridget Litts , Alexandra Duell , Patrick Elder , Stella M. Davies , Adam Lane , Michael B. Jordan , Sumithra Vasu , Steven Devine , Rebecca A. Marsh\",\"doi\":\"10.1016/j.tpr.2022.100100\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>We conducted a prospective validation study at Cincinnati Children's Hospital Medical Center and Ohio State University Medical Center to test if absolute CD38 bright CD8+TEM cells > 30/µL would predict acute GVHD, similar to our pilot data.</p></div><div><h3>Methods</h3><p>Blood was collected twice weekly following HSCT. If CD38 bright CD8+ TEM ≥ 30 cells/µL, Epstein-Barr virus and cytomegalovirus specificity was determined by tetramer staining, granzyme B content was assessed, Ki-67 staining performed to assess T-cell proliferation. 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引用次数: 0
摘要
我们在辛辛那提儿童医院医学中心和俄亥俄州立大学医学中心进行了一项前瞻性验证研究,以测试绝对CD38亮CD8+TEM细胞是否;30/µL可以预测急性GVHD,与我们的试点数据相似。方法HSCT术后每周采血2次。当CD38 bright CD8+ TEM≥30 cells/µL时,采用四聚体染色检测eb病毒和巨细胞病毒特异性,评估颗粒酶B含量,Ki-67染色检测t细胞增殖。体外用阿仑单抗、达拉单抗和环磷酰胺孵育细胞,以测定细胞对耗竭的敏感性。结果182例入组患者中,83例(45.6%)在第100天发生急性GVHD, 171例患者可评估(急性GVHD n = 77,无GVHD n = 94)。在临床症状出现之前,以及在CMV和EBV四聚体阳性患者被排除后,最大绝对CD38亮CD8+TEM细胞没有差异。Ki-67或颗粒酶B在急性GVHD患者和非急性GVHD患者中的表达具有可比性。最后,体外用阿仑单抗和环磷酰胺有效地耗尽CD38亮CD8+ t细胞。结论:在成人和儿童HSCT接受者的大型验证队列中,绝对外周血CD38亮CD8+TEM细胞≥30不能预测急性GVHD。
Prospective two center study of CD38 bright CD8+ effector memory T-cells as a predictor of acute GVHD
Introduction
We conducted a prospective validation study at Cincinnati Children's Hospital Medical Center and Ohio State University Medical Center to test if absolute CD38 bright CD8+TEM cells > 30/µL would predict acute GVHD, similar to our pilot data.
Methods
Blood was collected twice weekly following HSCT. If CD38 bright CD8+ TEM ≥ 30 cells/µL, Epstein-Barr virus and cytomegalovirus specificity was determined by tetramer staining, granzyme B content was assessed, Ki-67 staining performed to assess T-cell proliferation. Cells were incubated with alemtuzumab, daratumumab and cyclophosphamide in vitro to determine susceptibility to depletion.
Results
Of the 182 enrolled patients, 83 (45.6%) developed acute GVHD by day+100 but 171 patients were evaluable (acute GVHD n = 77 and no GVHD n = 94). There was no difference in the maximum absolute CD38 bright CD8+TEM cells prior to clinical symptoms and also after CMV and EBV tetramer positive patients were excluded from both cohorts. Ki-67 or Granzyme B expression in patients were comparable between patients with and without acute GVHD. Lastly CD38 bright CD8+ T-cells were effectively depleted with alemtuzumab and cyclophosphamide in vitro.
Conclusion
Absolute peripheral blood CD38 bright CD8+TEM cells ≥30 do not predict acute GVHD in a large validation cohort of adult and pediatric HSCT recipients.
期刊介绍:
To provide to national and regional audiences experiences unique to them or confirming of broader concepts originating in large controlled trials. All aspects of organ, tissue and cell transplantation clinically and experimentally. Transplantation Reports will provide in-depth representation of emerging preclinical, impactful and clinical experiences. -Original basic or clinical science articles that represent initial limited experiences as preliminary reports. -Clinical trials of therapies previously well documented in large trials but now tested in limited, special, ethnic or clinically unique patient populations. -Case studies that confirm prior reports but have occurred in patients displaying unique clinical characteristics such as ethnicities or rarely associated co-morbidities. Transplantation Reports offers these benefits: -Fast and fair peer review -Rapid, article-based publication -Unrivalled visibility and exposure for your research -Immediate, free and permanent access to your paper on Science Direct -Immediately citable using the article DOI