Takahashi Nobuhisa, Mochizuki Kazuhiro, Kikuta Atsushi, Ohara Yoshihiro, Kudo Shingo, Ikeda Kazuhiko, Ohto Hitoshi, Sano Hideki
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.
Int J Hematol. 2025 Mar;121(3):403-410. doi: 10.1007/s12185-024-03900-2. Epub 2024 Dec 10.
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.
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。