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移植后环磷酰胺介导异基因造血细胞移植后记忆 B 细胞的有效重建。

Posttransplantation cyclophosphamide mediates effective reconstitution of memory B cells after allogeneic hematopoietic cell transplantation.

机构信息

Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Department of Clinical Laboratory, Osaka Metropolitan University Hospital, Osaka, Japan.

出版信息

Eur J Haematol. 2024 Nov;113(5):651-663. doi: 10.1111/ejh.14280. Epub 2024 Jul 28.

Abstract

OBJECTIVES

Impaired B-cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT) contributes to the pathogenesis of chronic graft-versus-host disease (cGVHD). Therefore, methods to consistently achieve effective B cell lymphogenesis are required. We assessed the long-term effects of posttransplantation cyclophosphamide (PTCy) use on immune reconstitution in clinical settings, an emerging strategy to suppress allogeneic immunological inflammation early after allo-HCT and prevent subsequent GVHD.

METHODS

We comprehensively analyzed peripheral immune cell subsets and measured serum immunoglobulin G (IgG) or cytokine levels in 39 patients who survived for >1 year after allo-HCT.

RESULTS

The absolute counts of B1 and IgM memory B cells were significantly lower in patients with severe cGVHD than in those without. The absolute count and percentage (among total CD19+ B cells) of switched memory B cells and serum IgG levels were significantly higher in patients transplanted with PTCy than in those transplanted with conventional GVHD prophylaxis. Interestingly, increased percentages of switched memory B cells and serum IgG levels were observed only in patients transplanted with PTCy and not in those transplanted with umbilical cord blood.

CONCLUSIONS

PTCy administration can mediate favorable memory B-cell reconstitution long after allo-HCT and may therefore suppress cGVHD.

摘要

目的

异基因造血细胞移植(allo-HCT)后 B 细胞重建受损,导致慢性移植物抗宿主病(cGVHD)的发病机制。因此,需要有方法能够持续实现有效的 B 细胞淋巴生成。我们评估了移植后环磷酰胺(PTCy)在临床环境中对免疫重建的长期影响,这是一种在 allo-HCT 后早期抑制同种异体免疫炎症并预防随后发生 GVHD 的新兴策略。

方法

我们全面分析了 39 例 allo-HCT 后存活时间>1 年的患者的外周免疫细胞亚群,并测量了血清免疫球蛋白 G(IgG)或细胞因子水平。

结果

与无严重 cGVHD 的患者相比,严重 cGVHD 患者的 B1 和 IgM 记忆 B 细胞绝对计数明显较低。与接受常规 GVHD 预防的患者相比,接受 PTCy 移植的患者的记忆 B 细胞和 IgG 水平的绝对计数和百分比(占总 CD19+B 细胞)显著更高。有趣的是,仅在接受 PTCy 移植而不是接受脐带血移植的患者中观察到记忆 B 细胞百分比和 IgG 水平升高。

结论

PTCy 给药可介导 allo-HCT 后很长时间内的有利记忆 B 细胞重建,因此可能抑制 cGVHD。

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