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欧洲异基因干细胞移植后供体淋巴细胞输注的当前应用情况:代表欧洲血液与骨髓移植协会细胞治疗与免疫生物学工作组开展的一项调查

Current use of donor lymphocyte infusions after allogenic stem cell transplantation in Europe: a survey on behalf of the cellular therapy and immunobiology working party of the EBMT.

作者信息

Santoro Nicole, Schmid Christoph, de Witte Moniek, Roeven Mieke W H, Potter Victoria, Richardson Deborah, Schroeder Thomas, Válková Veronika, Clesham Katherine, Loron Sandrine, Passweg Jakob, Besley Caroline, Gruhn Bernd, Hoogenboom Jorinde D, Mooyaart Jarl E, Sanchez-Ortega Isabel, Pagliuca Simona, Simonetta Federico, Battipaglia Giorgia, Guillaume Thierry, Hazenberg Mette D, Malard Florent, Kuball Jürgen, Ruggeri Annalisa

机构信息

Hematology Unit, Department of Oncology and Hematology, Santo Spirito Hospital, Pescara, Italy.

Department of Hematology and Oncology, Augsburg University Hospital and Medical Faculty Comprehensive Cancer Center Augsburg and Bavarian Cancer Research Center, Augsburg, Germany.

出版信息

Bone Marrow Transplant. 2025 May;60(5):697-701. doi: 10.1038/s41409-025-02555-9. Epub 2025 Mar 23.

DOI:10.1038/s41409-025-02555-9
PMID:40123004
Abstract

Unmanipulated donor lymphocyte infusions (DLI) are crucial for enhancing the graft versus tumor (GVT) effect in post-transplant settings. Practices regarding DLI use vary widely among centers, encompassing differences in indications, prerequisites, and application methods. To explore current DLI policies, we developed a comprehensive survey that garnered responses from 165 EBMT centers across 43 countries. Notably, 97% of respondents reported using DLI in their practices. Indications for DLI included preemptive use for minimal residual disease (MRD) positivity in 86.9% of centers and mixed chimerism in 73.1%; therapeutic use for hematological relapse in 73.1%; and prophylactic use for high-risk disease in 43.8%. Active graft-versus-host disease (GVHD) and active infections were deemed absolute contraindications by 85.6% and 57.5% of centers, respectively. 35% of centers did not consider a prior history of acute (a)GVHD as an exclusion criterion. The majority (71.9%) requested immunosuppression withdrawal before DLI. Most centers (71.3%) collected DLI post-transplant, with 78.1% utilizing unstimulated apheresis. The cell doses applied at the first DLI varied significantly, depending on indication, timing, and donor type. This survey provides the largest overview of current DLI practices, highlighting the need for high-quality data to assess the risks and benefits of different approaches.

摘要

未处理的供体淋巴细胞输注(DLI)对于增强移植后环境中的移植物抗肿瘤(GVT)效应至关重要。各中心在DLI使用方面的做法差异很大,包括适应症、前提条件和应用方法的不同。为了探索当前的DLI政策,我们开展了一项全面调查,收集了来自43个国家165个欧洲血液与骨髓移植协会(EBMT)中心的回复。值得注意的是,97%的受访者报告在其实践中使用了DLI。DLI的适应症包括:86.9%的中心对微小残留病(MRD)阳性进行抢先使用,73.1%的中心对混合嵌合体进行使用;73.1%的中心对血液学复发进行治疗性使用;43.8%的中心对高危疾病进行预防性使用。85.6%和57.5%的中心分别将活动性移植物抗宿主病(GVHD)和活动性感染视为绝对禁忌症。35%的中心不将既往急性(a)GVHD病史作为排除标准。大多数(71.9%)中心要求在DLI前停用免疫抑制剂。大多数中心(71.3%)在移植后采集DLI,78.1%的中心使用未刺激的单采术。首次DLI应用的细胞剂量因适应症、时机和供体类型而异。这项调查提供了当前DLI实践的最大概述,强调了需要高质量数据来评估不同方法的风险和益处。

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本文引用的文献

1
Donor lymphocyte infusion after allogeneic haematopoietic cell transplantation for haematological malignancies: basic considerations and best practice recommendations from the EBMT.异基因造血细胞移植后供者淋巴细胞输注治疗血液系统恶性肿瘤:EBMT 的基本考虑和最佳实践推荐。
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2
Spectral flow cytometry cluster analysis of therapeutic donor lymphocyte infusions identifies T cell subsets associated with outcome in patients with AML relapse.治疗性供者淋巴细胞输注的光谱流式细胞术聚类分析鉴定出与 AML 复发患者结局相关的 T 细胞亚群。
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3
Defining the Role of Donor Lymphocyte Infusion in High-Risk Hematologic Malignancies.
明确供体淋巴细胞输注在高危血液系统恶性肿瘤中的作用
J Clin Oncol. 2021 Feb 10;39(5):397-418. doi: 10.1200/JCO.20.01719. Epub 2021 Jan 12.
4
A Retrospective Comparison of DLI and gDLI for Post-Transplant Treatment.供体淋巴细胞输注(DLI)与基因编辑供体淋巴细胞输注(gDLI)用于移植后治疗的回顾性比较
J Clin Med. 2020 Jul 12;9(7):2204. doi: 10.3390/jcm9072204.
5
Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant.在单倍体移植中,改良供体淋巴细胞输注后进行6至8周的免疫抑制可降低急性移植物抗宿主病,且不影响移植物抗白血病效应。
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6
Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation.风险分层指导下的供者淋巴细胞输注可降低异基因造血干细胞移植后标准风险急性白血病患者的复发率。
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7
The effect of G-CSF on lymphocyte subsets and CD34+ cells in allogeneic stem cell transplantation.粒细胞集落刺激因子对异基因干细胞移植中淋巴细胞亚群和CD34+细胞的影响。
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Graft-versus-leukemia reactions after bone marrow transplantation.骨髓移植后的移植物抗白血病反应。
Blood. 1990 Feb 1;75(3):555-62.
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Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.供体白细胞输注用于治疗骨髓移植患者复发性慢性粒细胞白血病。
Blood. 1990 Dec 15;76(12):2462-5.