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异基因外周血造血干细胞移植中移植后环磷酰胺和抗胸腺细胞球蛋白与环磷酰胺预防移植物抗宿主病的比较:T 细胞和 NK 效应细胞重建的比较。

Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution.

机构信息

Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France.

Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France.

出版信息

J Immunol. 2020 Sep 1;205(5):1441-1448. doi: 10.4049/jimmunol.2000578. Epub 2020 Aug 3.

DOI:10.4049/jimmunol.2000578
PMID:32747504
Abstract

A higher incidence of graft-versus-host disease (GVHD) has been observed after haploidentical hematopoietic stem cell transplantation (h-HSCT) with posttransplant cyclophosphamide (PTCY) using peripheral blood stem cells (PBSC) as a source of graft. Moreover, combining PTCY with antithymocyte globulin (ATG) may help to reduce GVHD incidence. In this study, early immune reconstitution, especially of T and NK cell compartments, was compared after both types of transplant (PTCY versus PTCY + ATG) investigate their influence on patient outcomes. This retrospective study included 58 adults who received a reduced intensity conditioning to PBSC h-HSCT with cyclosporine and mycophenolate mofetyl + PTCY ( = 32) or PTCY + ATG ( = 26) as GVHD prophylaxis. Both groups shared similar characteristics except for the median number of CD3 T cells infused, significantly higher for PTCY + ATG patients. Blood samples from all patients were collected three times a week from day 0 until day 30 then at day 60 and day 90/100 to evaluate T and NK cells reconstitution by flow cytometry. The results show that PTCY + ATG versus PTCY alone significantly limits the occurrence of acute grade 2-4 GVHD after reduced intensity conditioning PBSC h-HSCT, perhaps because of the combined effect of T and NK cell reconstitution. Indeed, although a slower T cell reconstitution with PTCY + ATG may limit GVHD occurrence, the quicker reconstitution of some NK cell subtypes may help with avoiding relapse. Larger prospective studies are needed to better determine which NK cell subsets may influence the incidence of relapse after h-HSCT and optimize donor selection.

摘要

异基因造血干细胞移植(HSCT)后移植物抗宿主病(GVHD)的发生率较高,使用外周血干细胞(PBSC)作为移植物来源时,使用环磷酰胺(PTCY)进行移植后。此外,联合使用 PTCY 和抗胸腺细胞球蛋白(ATG)可能有助于降低 GVHD 的发生率。在这项研究中,比较了两种移植方式(PTCY 与 PTCY+ATG)后早期免疫重建,特别是 T 和 NK 细胞的重建,以探讨它们对患者结局的影响。这项回顾性研究纳入了 58 例接受环孢素和吗替麦考酚酯+PTCY(n=32)或 PTCY+ATG(n=26)作为 GVHD 预防的 PBSC 异基因 HSCT 的成人患者。除 PTCY+ATG 患者输注的 CD3 T 细胞中位数明显更高外,两组患者具有相似的特征。所有患者均在 0 天至 30 天内每周采集 3 次血液样本,然后在 60 天、90/100 天评估 T 和 NK 细胞重建。结果显示,与 PTCY 相比,PTCY+ATG 可显著限制 PBSC 异基因 HSCT 后低强度预处理后 2-4 级急性 GVHD 的发生,这可能是由于 T 和 NK 细胞重建的联合作用。确实,尽管 PTCY+ATG 会导致较慢的 T 细胞重建,但某些 NK 细胞亚群的快速重建可能有助于避免复发。需要更大的前瞻性研究来更好地确定哪些 NK 细胞亚群可能影响 HSCT 后复发的发生率,并优化供者选择。

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