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异基因骨髓移植后多发性骨髓瘤复发时的造血供体嵌合现象及移植物抗骨髓瘤效应

Hematopoietic donor chimerism and graft-versus-myeloma effect in relapse of multiple myeloma after allogeneic bone marrow transplantation.

作者信息

Keil F, Kalhs P, Chen X, Haas O A, Fritsch G, Chott A, Lechner K, Moser K, Ackermann J, Rabitsch W, Worel N, Mannhalter C, Greinix H T

机构信息

Department of Medicine 1, Bone Marrow Transplantation Unit, University of Vienna, Austria.

出版信息

Ann Hematol. 1999 Aug;78(8):376-9. doi: 10.1007/s002770050532.

DOI:10.1007/s002770050532
PMID:10460352
Abstract

A large group of patients relapsing after allogeneic bone marrow transplantation (BMT) have obtained remission after infusion of leukocytes from their original donor, suggesting a graft-versus-myeloma effect. However, side effects such as graft-versus-host disease and myelosuppression are severe, and sometimes fatal, complications of this therapeutic approach. Previously we demonstrated that patients with leukemia who lack donor hematopoiesis in relapse after BMT experience severe and lasting aplasia after infusion of donor leukocytes. In two patients - one with extramedullary and one with marrow relapse after a sex-mismatched transplantation - we analyzed hematopoietic chimerism by cell sorting and bone marrow cultures. CD34-positive cells, CD4-CD8-positive cells, committed progenitors, and LTC-IC were of donor origin, as demonstrated by two-color fluorescence in situ hybridization (FISH). Additionally, in relapse complete donor T-cell chimerism was seen. In contrast, plasma cells were of recipient origin in the patient who had a relapse in the bone marrow. Both patients were treated with infusions of donor leukocytes from their original donor. Neither patient suffered myelosuppression, and one achieved a stable complete remission.

摘要

一大群异基因骨髓移植(BMT)后复发的患者在输注来自其原始供体的白细胞后获得了缓解,提示存在移植物抗骨髓瘤效应。然而,移植物抗宿主病和骨髓抑制等副作用是这种治疗方法严重且有时致命的并发症。此前我们证明,BMT后复发且缺乏供体造血的白血病患者在输注供体白细胞后会经历严重且持久的再生障碍。在两名患者中——一名是在性别不匹配移植后出现髓外复发,另一名是骨髓复发——我们通过细胞分选和骨髓培养分析了造血嵌合体。双色荧光原位杂交(FISH)显示,CD34阳性细胞、CD4 - CD8阳性细胞、定向祖细胞和长期培养起始细胞(LTC - IC)均来自供体。此外,在复发时可见完全的供体T细胞嵌合体。相比之下,骨髓复发患者的浆细胞来自受体。两名患者均接受了来自其原始供体的供体白细胞输注。两名患者均未出现骨髓抑制,其中一名实现了稳定的完全缓解。

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1
Hematopoietic donor chimerism and graft-versus-myeloma effect in relapse of multiple myeloma after allogeneic bone marrow transplantation.异基因骨髓移植后多发性骨髓瘤复发时的造血供体嵌合现象及移植物抗骨髓瘤效应
Ann Hematol. 1999 Aug;78(8):376-9. doi: 10.1007/s002770050532.
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Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma.供体淋巴细胞输注后转化为完全供体嵌合状态与多发性骨髓瘤患者的疾病反应相关。
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Graft-versus-myeloma effect in two cases.两例移植物抗骨髓瘤效应
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Donor leukocyte infusion for leukemic relapse after allogeneic marrow transplantation: lack of residual donor hematopoiesis predicts aplasia.异基因骨髓移植后白血病复发时输注供体白细胞:缺乏残留供体造血功能预示着再生障碍。
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Detection of mixed chimerism and leukemic relapse after allogeneic bone marrow transplantation in subpopulations of leucocytes by fluorescent in situ hybridization in combination with the simultaneous immunophenotypic analysis of interphase cells.通过荧光原位杂交结合间期细胞的同步免疫表型分析检测异基因骨髓移植后白细胞亚群中的混合嵌合体和白血病复发。
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Transplantation of autologous and allogeneic bone marrow with liver from a cadaveric donor for primary liver cancer.采用来自尸体供体的肝脏进行自体和异体骨髓移植治疗原发性肝癌。
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Biol Blood Marrow Transplant. 2013 Oct;19(10):1509-13. doi: 10.1016/j.bbmt.2013.08.001. Epub 2013 Aug 13.
2
Ultra-short course sirolimus contributes to effective GVHD prophylaxis after reduced-intensity allogeneic hematopoietic cell transplantation.超短疗程西罗莫司有助于降低强度异基因造血细胞移植后移植物抗宿主病的有效预防。
Bone Marrow Transplant. 2012 Dec;47(12):1552-7. doi: 10.1038/bmt.2012.63. Epub 2012 Apr 23.
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EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT.
EPOCH-F:在降低强度异基因造血干细胞移植前治疗多发性骨髓瘤的新型挽救方案。
Bone Marrow Transplant. 2011 May;46(5):676-81. doi: 10.1038/bmt.2010.173. Epub 2010 Jul 26.