研究动态
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造血干细胞移植后小儿受者接受高剂量记忆 CD45RO 供体淋巴细胞输注的安全性和有效性。

Safety and Efficacy of High-Dose Memory CD45RO+ Donor Lymphocyte Infusion in Pediatric Recipients after Hematopoietic Stem Cell Transplantation.

发表日期:2024 Jul 11
作者: Mercedes Gasior Kabat, Ying Li, Victor Galán, Yasmina Mozo, Luisa Sisinni, David Bueno-Sánchez, Dolores Corral, Swati Naik, Carlos Echecopar, Cristina Aguirre-Portolés, Karima Al-Akioui-Sanz, Raquel De Paz, Antonio Marcos, Ana Belén Romero, Aimee Talleur, Víctor Jiménez Yuste, Brandon Triplett, Antonio Pérez-Martínez
来源: CYTOTHERAPY

摘要:

与初始 T 细胞相比,记忆 T 选择细胞 (CD45RA-/RO ) 作为供体淋巴细胞输注时产生同种异体反应性和移植物抗宿主病 (GvHD) 的能力较差。本研究的目的是评估异基因造血细胞移植(HCT)后高剂量记忆(CD45RA-/RO)供体淋巴细胞输注(mDLI)的安全性和有效性。 mDLI 的适应症是“根据需要”和“作为预防性治疗方案”。 61 名被诊断患有恶性疾病 (82%) 和非恶性疾病 (18%) 的儿童接受了 241 mDLI。患者平均接受 3 次 mDLI 输注(范围 1-13),中位输注剂量为 1.35 × 107/kg CD45RO,其中包含 8.96 × 106/kg CD3 CD45RO 和 3.81 × 103/kg CD3 CD45RA。 7 名患者在 4% 的 mDLI 输注后出现新发 GvHD。在 mDLI 之前患有 GvHD 的患者中,3 名 II-IV 级急性 GvHD 患者在 6 次输注后病情恶化(11%)。 65% 的 mDLI 输注后巨细胞病毒病毒载量下降。整个队列的两年总生存率 (OS) 为 64%(95% CI 57%−72%)。对于接受预防性 mDLI 的患者,两年无复发死亡率为 10%(95% CI 9%−11%)。综上所述,大剂量mDLI是可行且安全的,即使对于活动性GvHD患者,发生严重GvHD的风险也相对较低。重要的是,mDLI 与积极作用相关,包括增强对 CMV 病毒血症的控制。版权所有 © 2024 国际细胞学会
Memory T selected cells (CD45RA-/RO+) as donor lymphocyte infusion are less capable of producing alloreactivity and graft versus host disease (GvHD) compared with naïve T cells. The objective of this study was to evaluate the safety and efficacy of high-dose memory (CD45RA-/RO+) donor lymphocyte infusion (mDLI) after allogeneic hematopoietic cell transplantation (HCT). Indications for mDLI were "as needed" and "as prophylactic regimen." Sixty-one children diagnosed with malignant (82%) and non-malignant diseases (18%) received 241 mDLIs. Patients received a median of three infusions (range 1‒13) of mDLI with a median infused dose of 1.35 × 107/kg CD45RO+ containing 8.96 × 106/kg CD3+CD45RO+ and 3.81 × 103/kg CD3+CD45RA+. De novo GvHD developed in 7 patients following 4% of the mDLI infusions. Among patients with GvHD before mDLI, this condition worsened following 6 infusions (11%) in the 3 patients with grade II-IV acute GvHD. A decrease in cytomegalovirus viral load followed 65% of mDLI infusions. Two-year overall survival (OS) for the total cohort was 64% (95% CI 57%‒72%). For patients receiving prophylactic mDLI, the two-year non-relapse mortality was 10% (95% CI 9%‒11%). In summary, high-dose mDLI is feasible and safe, with a relatively low risk of severe GvHD even in patients with active GvHD. Importantly, mDLI was associated with positive effects, including enhanced control of CMV viremia.Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.