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静脉注射免疫球蛋白、地塞米松和高剂量单核细胞输注联合应用:一种在单倍体造血干细胞移植期间降低供者特异性抗体的有效策略。

The Combination of Intravenous Immunoglobulin, Dexamethasone, and a High Dose of Mononuclear Cells Transfusion: An Effective Strategy for Decreasing Donor-Specific Antibodies During Haploidentical Hematopoietic Stem Cell Transplantation.

作者信息

Li Xiaoping, Li Yu, Zhang Dingsong, Hu Xiaozhuang, Liu Lin, Yuan Zhongtao, Li Shiqi, Dong Yancheng, Chen Yingnian, Wang Sanbin

机构信息

Department of Hematology, 920th Hospital of Joint Logistics Support Force, Kunming, China.

Shanghai Tissuebank Biotechnology Co., Ltd, Shanghai, China.

出版信息

Cell Transplant. 2025 Jan-Dec;34:9636897241303292. doi: 10.1177/09636897241303292.

DOI:10.1177/09636897241303292
PMID:39874071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11775969/
Abstract

Donor-specific antibodies (DSAs) are essential causes of graft rejection in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). DSAs are unavoidable for some patients who have no alternative donor. Effective interventions to reduce DSAs are still needed, and the cost of the current therapies is relatively high. In this study, we retrospectively analyzed the data of 11 DSA-positive patients who received haplo-HSCT at our center and evaluated the therapeutic efficacy of the combination of intravenous immunoglobulin (IVIG), dexamethasone and high dose of transfused mononuclear cells (MNCs) for DSA desensitization. The kinetics of DSAs at different times and the engraftment and transplantation outcomes were also observed. We found that all patients had successful donor-cell engraftment and that no patient developed poor graft function. The median engraftment times of neutrophils and platelets were 14 days (range, 11-24 days) and 13 days (range, 11-123 days), respectively. The DSA levels of all patients became negative or dropped under 2000 within 22 days after HSCT. A total of 36.4% of patients developed grade II-IV acute graft-versus-host disease (aGVHD), and 9.1% of patients died of severe gastrointestinal aGVHD. Of the 7 surviving patients, four were diagnosed with chronic GVHD. After a median follow-up of 28.9 months (2.0-52.1 months), four patients died: of relapse (two), aGVHD (one), and multiple-organ failure (one). The 2-year OS, DFS, and NRM were 63.6%, 45.4%, and 18.2%, respectively. Combination therapy with IVIG, dexamethasone, and a high dose of MNCs transfusion, a simple and efficient procedure, was safe and effective for DSA desensitization and peripheral blood stem cell (PBSC) engraftment.

摘要

供者特异性抗体(DSA)是单倍体相合造血干细胞移植(haplo-HSCT)中移植物排斥反应的重要原因。对于一些没有其他供者选择的患者来说,DSA是不可避免的。仍需要有效的干预措施来降低DSA,而目前治疗方法的费用相对较高。在本研究中,我们回顾性分析了在我们中心接受haplo-HSCT的11例DSA阳性患者的数据,并评估了静脉注射免疫球蛋白(IVIG)、地塞米松和高剂量输注单个核细胞(MNC)联合用于DSA脱敏的治疗效果。还观察了不同时间DSA的变化动态以及植入和移植结局。我们发现所有患者的供者细胞均成功植入,且无患者发生移植物功能不良。中性粒细胞和血小板的中位植入时间分别为14天(范围11 - 24天)和13天(范围11 - 123天)。所有患者的DSA水平在HSCT后22天内均转为阴性或降至2000以下。共有36.4%的患者发生了II - IV级急性移植物抗宿主病(aGVHD),9.1%的患者死于严重的胃肠道aGVHD。在7例存活患者中,4例被诊断为慢性GVHD。中位随访28.9个月(2.0 - 52.1个月)后,4例患者死亡:2例死于复发,1例死于aGVHD,1例死于多器官功能衰竭。2年总生存率(OS)、无病生存率(DFS)和非复发死亡率(NRM)分别为63.6%、45.4%和18.2%。IVIG、地塞米松和高剂量MNC输注的联合治疗是一种简单有效的方法,对DSA脱敏和外周血干细胞(PBSC)植入安全有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/5183259d8d71/10.1177_09636897241303292-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/f07a771fb387/10.1177_09636897241303292-img2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/2fa53bcfcc4f/10.1177_09636897241303292-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/9cb1e7a3e436/10.1177_09636897241303292-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/5183259d8d71/10.1177_09636897241303292-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/f07a771fb387/10.1177_09636897241303292-img2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/2fa53bcfcc4f/10.1177_09636897241303292-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/9cb1e7a3e436/10.1177_09636897241303292-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e15b/11775969/5183259d8d71/10.1177_09636897241303292-fig3.jpg

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本文引用的文献

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[Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases].鲁索替尼联合小剂量PTCY预防恶性血液病单倍体移植后急性移植物抗宿主病的疗效临床研究
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Targeting T cells is a novel approach for donor-specific antibody desensitization of allograft candidates: an and study.靶向 T 细胞是一种用于同种异体移植物候选者的供体特异性抗体脱敏的新方法:一项前瞻性和回顾性研究。
Haematologica. 2024 Apr 1;109(4):1233-1246. doi: 10.3324/haematol.2023.283698.
3
Treatment With the Combination of Rituximab and Intravenous γ Globulin Is Effective in Promoting Engraftment in Donor-Specific Antibody Positive Patients Receiving Myeloablative Conditioning Haploidentical Stem Cell Transplantation.
利妥昔单抗联合静脉注射丙种球蛋白治疗在接受清髓性单倍体造血干细胞移植的供体特异性抗体阳性患者中促进植入是有效的。
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Splenic irradiation combined with plasmapheresis and rituximab: a new option reducing donor-specific antibody in haploidentical hematopoietic stem cell transplantation.脾照射联合血浆置换和利妥昔单抗:一种降低单倍体造血干细胞移植中供者特异性抗体的新选择。
Bone Marrow Transplant. 2023 Feb;58(2):226-228. doi: 10.1038/s41409-022-01868-3. Epub 2022 Nov 19.
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