Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.
Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.
Transplant Cell Ther. 2022 Mar;28(3):152.e1-152.e7. doi: 10.1016/j.jtct.2021.12.017. Epub 2021 Dec 29.
Mixed chimerism (MC) and secondary graft failure (SGF) with recipient- or donor-type chimerism is a major obstacle in allogeneic hematopoietic stem cell transplantation (HSCT). Donor lymphocyte infusion (DLI) can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions after HSCT. This study aimed to analyze the efficacy and immune mechanism of DLI from the original and alternative donor for patients of mixed donor chimerism with SGF. The alternative donor refers to the candidate relative donor who did not initially provide stem cells and includes HLA-matched sibling donor or HLA-haploidentical donor. We conducted a retrospective study of 246 patients with a median age of 37 (9-58) years who had regularly detected MC, complete donor chimera (CC), and regulatory T cells (Treg). The median diagnosis time of SGF was 69 (39-141) days after transplantation. Sixteen patients with SGF received DLI from the alternative donor, including 3 patients who chose DLI from the original donor with no initial response and 13 patients who directly chose DLI from the alternative donor. Sixteen patients with SGF existed mixed chimerism synchronously and the rate calculated overall chimerism of MC was 63% (range 42%-85%) after transplantation. The proportion of Treg decreased significantly in SGF patients from a median of 2.66% ± 0.80% to 0.93% ± 0.57% at a time point after transplantation (P = .02). The DLI of the alternative donor in 14 patients achieved complete response and MC gradually convert to CC state, simultaneously there was significant increase in the Treg fraction (SGF versus complete response: 0.93% ± 0.57% versus 3.61% ± 0.82% [P = .01]). For the clinical nonresponders from 2 types of donors, there was no significant change in MC and Treg cells. The OS and disease-free survival at 2 years after DLI were 69.7% ± 3.19% and 61.3% ± 4.80%, respectively. DLI from the alternative donor may be an effective treatment for MC with SGF, and the mechanism is closely related to the activation of Treg cells level.
嵌合状态（MC）和受者或供者来源嵌合体的二次移植物失败（SGF）是异基因造血干细胞移植（HSCT）的主要障碍。供者淋巴细胞输注（DLI）可清除微小残留疾病或用于挽救血液学复发，能够在 HSCT 后诱导持久缓解。本研究旨在分析供者来源嵌合体伴 SGF 的患者中来自原始供者和替代供者的 DLI 的疗效和免疫机制。替代供者是指最初未提供干细胞的候选亲缘供者，包括 HLA 匹配的同胞供者或 HLA 单倍体相合供者。我们对 246 例中位年龄为 37（9-58）岁的患者进行了回顾性研究，这些患者定期检测到 MC、完全供者嵌合体（CC）和调节性 T 细胞（Treg）。SGF 的中位诊断时间是移植后 69（39-141）天。16 例 SGF 患者接受了来自替代供者的 DLI，其中 3 例患者最初对 DLI 无反应，选择了来自原始供者的 DLI，13 例患者直接选择了来自替代供者的 DLI。16 例 SGF 患者同时存在混合嵌合体，移植后整体嵌合体 MC 的计算率为 63%（范围 42%-85%）。SGF 患者的 Treg 比例从移植后中位值 2.66%±0.80%显著下降至 0.93%±0.57%（P=0.02）。14 例患者的替代供者 DLI 达到完全缓解，MC 逐渐转化为 CC 状态，同时 Treg 分数显著增加（SGF 与完全缓解：0.93%±0.57%与 3.61%±0.82%[P=0.01]）。对于来自 2 种供者的临床无反应者，MC 和 Treg 细胞没有明显变化。DLI 后 2 年的 OS 和无病生存率分别为 69.7%±3.19%和 61.3%±4.80%。来自替代供者的 DLI 可能是伴 SGF 的 MC 的有效治疗方法，其机制与 Treg 细胞水平的激活密切相关。
