Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Bone Marrow Transplant. 2021 Apr;56(4):900-908. doi: 10.1038/s41409-020-01128-2. Epub 2020 Nov 17.
The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts.A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 10 to 100 × 10/kg (haplo) and from 100 × 10 to 300 × 10 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire.In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.
适应性免疫的延迟恢复是αβ T 细胞耗竭造血干细胞移植（HSCT）后与移植相关的死亡率（TRM）的基础。我们测试了在αβ T 细胞耗竭移植物植入后使用低剂量记忆供体淋巴细胞输注（mDLI）。
一个由 131 名儿科患者组成的队列（中位年龄 9 岁）接受了来自半相合（n=79）或无关供体（n=52）的αβ T 细胞耗竭产品的移植。植入后，患者接受了通过 CD45RA 耗竭制备的 mDLI。细胞剂量每月从 25×10 增加到 100×10/kg（半相合）和从 100×10 增加到 300×10/kg（MUD）。在 16 名患者的亚队列中，使用深度测序对 T 细胞受体（TCR）谱进行了分析，以跟踪 T 细胞克隆，并评估 mDLI 对免疫谱的贡献。
共进行了 343 次 mDLI。新发 II 级和 III 级急性移植物抗宿主病（aGVHD）的累积发生率（CI）分别为 5%和 2%，慢性移植物抗宿主病的 CI 为 7%。在 mDLI 前无法检测到 CMV 特异性 T 细胞的一半患者恢复了 CMV 特异性 T 细胞。TCR 谱分析证实，mDLI 衍生的 T 细胞在 HSCT 后长达 1 年显著有助于 TCR 谱，包括持续存在的、CMV 特异性 T 细胞克隆。
