Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Department of Clinical Laboratory, Osaka Metropolitan University Hospital, Osaka, Japan.
Eur J Haematol. 2024 Nov;113(5):651-663. doi: 10.1111/ejh.14280. Epub 2024 Jul 28.
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.
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.
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.
PTCy administration can mediate favorable memory B-cell reconstitution long after allo-HCT and may therefore suppress cGVHD.
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。
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。
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。
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。