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移植CD8 T细胞以改善血液系统恶性肿瘤患儿在T细胞充足的单倍体同基因干细胞移植后的无事件生存期。

Graft CD8 T cells for improving event-free survival after T cell-replete haploidentical stem cell transplantation in children with hematological malignancies.

作者信息

Takahashi Nobuhisa, Mochizuki Kazuhiro, Kikuta Atsushi, Ohara Yoshihiro, Kudo Shingo, Ikeda Kazuhiko, Ohto Hitoshi, Sano Hideki

机构信息

Department of Pediatric Oncology, Fukushima Medical University Hospital, 1 Hikariga-oka, Fukushima City, 960-1295, Japan.

Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, 1 Hikariga-oka, Fukushima City, 960-1295, Japan.

出版信息

Int J Hematol. 2025 Mar;121(3):403-410. doi: 10.1007/s12185-024-03900-2. Epub 2024 Dec 10.

Abstract

T cell-replete haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) is a potentially curative therapy for pediatric intractable hematological malignancies due to its graft-versus-leukemia efficacy. This single-center cohort study examined the effects of graft composition (T cell type and dose) on pediatric TCR-haplo-HSCT outcomes in 32 children with relapsed/intractable hematological malignancies. Graft T cell composition was classified using flow cytometry. High graft CD8 T cell doses reduced disease relapse and improved overall survival and event-free survival, but did not increase transplant-related mortality and the incidence of grade III/IV acute graft-versus-host disease. Doses of grafted CD3, CD4, and CD34 T cells did not affect patient outcomes. Children with differing event-free survival times were divided by a graft CD8 T cell dose cut-off of 2.03 × 10 kg. These findings revealed that grafted CD8 T cells improved the graft-versus-leukemia effect of pediatric TCR-haplo-HSCT without increasing the risk of transplant-related mortality.

摘要

T细胞充足的单倍体相合造血干细胞移植(TCR-单倍体-HSCT)因其移植物抗白血病疗效,是治疗儿童难治性血液系统恶性肿瘤的一种潜在治愈性疗法。这项单中心队列研究调查了移植物组成(T细胞类型和剂量)对32例复发/难治性血液系统恶性肿瘤儿童TCR-单倍体-HSCT结局的影响。采用流式细胞术对移植物T细胞组成进行分类。高剂量的移植物CD8 T细胞可降低疾病复发率,提高总生存率和无事件生存率,但不会增加移植相关死亡率和III/IV级急性移植物抗宿主病的发生率。移植的CD3、CD4和CD34 T细胞剂量不影响患者结局。无事件生存时间不同的儿童按移植物CD8 T细胞剂量临界值2.03×10⁶/kg进行划分。这些发现表明,移植的CD8 T细胞可改善儿童TCR-单倍体-HSCT的移植物抗白血病效应,而不会增加移植相关死亡风险。

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