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

IF 2.3 3区 医学 Q2 HEMATOLOGY European Journal of Haematology Pub Date : 2024-07-28 DOI:10.1111/ejh.14280
Tetsuya Hayashi, Yasuhiro Nakashima, Shinichi Takeda, Mitsutaka Nishimoto, Hiroshi Okamura, Teruhito Takakuwa, Masatomo Kuno, Yosuke Makuuchi, Kentaro Ido, Kazuki Sakatoku, Mirei Horiuchi, Hideo Koh, Mika Nakamae, Masayuki Hino, Hirohisa Nakamae
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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.

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异体造血细胞移植后,移植后环磷酰胺介导记忆 B 细胞的有效重建。
目的:异基因造血细胞移植(allo-HCT)后 B 细胞重建受损是慢性移植物抗宿主病(cGVHD)的发病机制之一。因此,我们需要持续有效地实现 B 细胞淋巴生成的方法。我们评估了移植后使用环磷酰胺(PTCy)对临床环境中免疫重建的长期影响,这是异体HCT后早期抑制异体免疫炎症并预防后续GVHD的一种新兴策略:我们对异体肝移植后存活超过一年的 39 例患者的外周免疫细胞亚群进行了全面分析,并测量了血清免疫球蛋白 G (IgG) 或细胞因子水平:结果:重度 cGVHD 患者 B1 和 IgM 记忆 B 细胞的绝对数量明显低于非重度 cGVHD 患者。PTCy移植患者的转换记忆B细胞绝对数量和百分比(在CD19+ B细胞总数中)以及血清IgG水平均明显高于采用传统GVHD预防措施的移植患者。有趣的是,仅在使用 PTCy 移植的患者中观察到切换记忆 B 细胞百分比和血清 IgG 水平的增加,而在使用脐带血移植的患者中未观察到:结论:在allo-HCT 后很长时间内,PTCy 可以促进记忆 B 细胞的重建,因此可以抑制 cGVHD。
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来源期刊
CiteScore
5.50
自引率
0.00%
发文量
168
审稿时长
4-8 weeks
期刊介绍: European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
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