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配偶造血干细胞移植

Spousal hematopoietic stem cell transplantation.

作者信息

Ikegame Kazuhiro, Kaida Katsuji, Yoshihara Satoshi, Yoshihara Kyoko, Ishii Shinichi, Inoue Takayuki, Okada Masaya, Tamaki Hiroya, Soma Toshihiro, Kusunoki Yasushi, Kojima Hiroto, Saji Hiroh, Ogawa Hiroyasu

机构信息

Division of Hematology, Department of Internal Medicine, Hyogo Medical College, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

Department of Transfusion Medicine and Cell Therapy, Hyogo Medical College, Nishinomiya, Hyogo, Japan.

出版信息

Int J Hematol. 2017 May;105(5):646-657. doi: 10.1007/s12185-016-2168-y. Epub 2016 Dec 24.

DOI:10.1007/s12185-016-2168-y
PMID:28013483
Abstract

We report a pilot series of five patients who received stem cell transplantation (SCT) from a spouse for post-transplant relapse or rejection. The inclusion criterion regarding HLA disparities was three or fewer antigen mismatches in the graft-versus-host direction at the HLA-A, B, and DR loci. Four patients received spousal SCT as a third transplant attempt after post-transplant relapse and one as rescue for graft rejection. The reduced intensity conditioning (RIC) regimen consisted of fludarabine, melphalan, and anti-thymocyte globulin (ATG) with 3 Gy of total body irradiation (TBI) for relapse cases and ATG plus 4 Gy of TBI for the rejection case. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. Peripheral blood stem cells were transplanted. Granulocyte engraftment was achieved in all cases between days 9 and 11 (median, 10) with complete spousal chimerism. In three of the five patients, no acute GVHD was observed, while one case developed grade III GVHD and one case grade IV. All four patients evaluable for the anti-leukemic effect achieved complete remission; however, all relapsed between 106 and 334 day post-transplant, and died between days 152 and 548. We suggest that spousal SCT can be performed as a repetitive SCT using a RIC regimen with low-dose ATG and steroid-containing GVHD prophylaxis.

摘要

我们报告了一个由五名患者组成的试点系列,这些患者因移植后复发或排斥反应接受了来自配偶的干细胞移植(SCT)。关于HLA差异的纳入标准是在HLA - A、B和DR位点上,移植物抗宿主方向的抗原错配为三个或更少。四名患者在移植后复发后接受配偶SCT作为第三次移植尝试,一名患者接受配偶SCT以挽救移植排斥反应。低强度预处理(RIC)方案包括氟达拉滨、美法仑和抗胸腺细胞球蛋白(ATG),复发患者接受3 Gy全身照射(TBI),排斥反应患者接受ATG加4 Gy TBI。移植物抗宿主病(GVHD)预防包括他克莫司、甲基泼尼松龙和霉酚酸酯。移植的是外周血干细胞。所有病例在第9天至第11天(中位数为10天)实现了粒细胞植入,并伴有完全的配偶嵌合体。五名患者中有三名未观察到急性GVHD,一名患者发生了III级GVHD,一名患者发生了IV级GVHD。所有四名可评估抗白血病效果的患者均实现了完全缓解;然而,所有患者均在移植后106天至334天之间复发,并在第152天至548天之间死亡。我们建议配偶SCT可以作为重复SCT进行,采用含低剂量ATG和类固醇的GVHD预防的RIC方案。

相似文献

1
Spousal hematopoietic stem cell transplantation.配偶造血干细胞移植
Int J Hematol. 2017 May;105(5):646-657. doi: 10.1007/s12185-016-2168-y. Epub 2016 Dec 24.
2
Low-dose total body irradiation, fludarabine, and antithymocyte globulin conditioning for nonmyeloablative allogeneic transplantation.低剂量全身照射、氟达拉滨和抗胸腺细胞球蛋白预处理用于非清髓性异基因移植。
Biol Blood Marrow Transplant. 2003 Jul;9(7):453-9. doi: 10.1016/s1083-8791(03)00139-3.
3
Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning.采用非清髓性预处理的未处理的HLA 2-3抗原错配(半相合)干细胞移植。
Biol Blood Marrow Transplant. 2006 Oct;12(10):1073-84. doi: 10.1016/j.bbmt.2006.06.007.
4
Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant.对于先前造血干细胞移植后复发的晚期血液系统恶性肿瘤患者,采用氟达拉滨和美法仑进行预处理。
Bone Marrow Transplant. 2001 Sep;28(6):557-62. doi: 10.1038/sj.bmt.1703198.
5
Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT.预处理强度对T细胞充足的单倍体相合干细胞移植治疗急性白血病的影响:欧洲血液与骨髓移植协会急性白血病工作组的报告
J Hematol Oncol. 2016 Mar 15;9:25. doi: 10.1186/s13045-016-0248-3.
6
Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society.氟达拉滨联合2 Gy全身照射或抗胸腺细胞球蛋白联合8 Gy胸腺照射后的非清髓性异基因造血细胞移植:比利时血液学会的一项II期随机研究
J Hematol Oncol. 2015 Feb 6;8:4. doi: 10.1186/s13045-014-0098-9.
7
A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia.在成年急性髓系白血病患者中,一种耐受性良好的800厘戈瑞全身照射-氟达拉滨-白消安-抗胸腺细胞球蛋白方案用于非处理单倍体相合外周血干细胞移植后可靠植入。
Biol Blood Marrow Transplant. 2015 Jan;21(1):119-29. doi: 10.1016/j.bbmt.2014.09.029. Epub 2014 Oct 6.
8
Unmanipulated Haploidentical Reduced-Intensity Stem Cell Transplantation Using Fludarabine, Busulfan, Low-Dose Antithymocyte Globulin, and Steroids for Patients in Non-Complete Remission or at High Risk of Relapse: A Prospective Multicenter Phase I/II Study in Japan.使用氟达拉滨、白消安、低剂量抗胸腺细胞球蛋白和类固醇对未完全缓解或复发高危患者进行非处理单倍体相合减低强度干细胞移植:日本一项前瞻性多中心I/II期研究
Biol Blood Marrow Transplant. 2015 Aug;21(8):1495-505. doi: 10.1016/j.bbmt.2015.04.012. Epub 2015 Apr 25.
9
A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome.对于骨髓增生异常综合征患者,采用基于氟达拉滨的剂量降低预处理方案,随后接受来自相关或无关供体的异基因干细胞移植。
Bone Marrow Transplant. 2001 Oct;28(7):643-7. doi: 10.1038/sj.bmt.1703215.
10
Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan.异基因造血干细胞移植前两种基于氟达拉滨的减低强度预处理方案的比较:与氟达拉滨/白消安相比,氟达拉滨/美法仑与更高的急性移植物抗宿主病发生率和非复发死亡率以及更低的复发率相关。
Leukemia. 2007 Oct;21(10):2109-16. doi: 10.1038/sj.leu.2404886. Epub 2007 Aug 9.

引用本文的文献

1
Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study.来自2个HLA单倍型不匹配的家庭供体的异基因造血干细胞移植治疗移植后复发:一项前瞻性I/II期研究。
Bone Marrow Transplant. 2021 Jan;56(1):70-83. doi: 10.1038/s41409-020-0980-8. Epub 2020 Jun 20.

本文引用的文献

1
Effect of major histocompatibility complex haplotype matching by C4 and MICA genotyping on acute graft versus host disease in unrelated hematopoietic stem cell transplantation.通过C4和MICA基因分型进行主要组织相容性复合体单倍型匹配对非亲缘造血干细胞移植中急性移植物抗宿主病的影响。
Hum Immunol. 2016 Feb;77(2):176-83. doi: 10.1016/j.humimm.2015.11.015. Epub 2015 Nov 18.
2
Unmanipulated Haploidentical Reduced-Intensity Stem Cell Transplantation Using Fludarabine, Busulfan, Low-Dose Antithymocyte Globulin, and Steroids for Patients in Non-Complete Remission or at High Risk of Relapse: A Prospective Multicenter Phase I/II Study in Japan.使用氟达拉滨、白消安、低剂量抗胸腺细胞球蛋白和类固醇对未完全缓解或复发高危患者进行非处理单倍体相合减低强度干细胞移植:日本一项前瞻性多中心I/II期研究
Biol Blood Marrow Transplant. 2015 Aug;21(8):1495-505. doi: 10.1016/j.bbmt.2015.04.012. Epub 2015 Apr 25.
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The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT.高连锁不平衡中频繁 HLA 单倍型对无关造血干细胞移植后供者搜索和临床结局的影响。
Bone Marrow Transplant. 2013 Apr;48(4):483-90. doi: 10.1038/bmt.2012.189. Epub 2012 Oct 15.
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Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study.在移植物抗宿主病方向上与 HLA-1Ag 不匹配,以及在 HLA-8/8 等位基因匹配的非亲缘移植中进行相关移植:一项全国性回顾性研究。
Blood. 2012 Mar 8;119(10):2409-16. doi: 10.1182/blood-2011-08-372573. Epub 2011 Oct 31.
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Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT.预先存在的供者特异性 HLA 抗体患者行非清除性单倍体相合造血干细胞移植后移植物失功的风险和预防。
Bone Marrow Transplant. 2012 Apr;47(4):508-15. doi: 10.1038/bmt.2011.131. Epub 2011 Jun 20.
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Loss of mismatched HLA in leukemia after stem-cell transplantation.干细胞移植后白血病中错配HLA的丢失。
N Engl J Med. 2009 Jul 30;361(5):478-88. doi: 10.1056/NEJMoa0811036.
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Transplantation of ABO-incompatible and living unrelated donor-recipient combinations.ABO血型不相容及活体非亲属供受者组合的移植。
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The excellent results of spousal kidney transplantation: experience in a Japanese single center.配偶肾移植的卓越成果:日本单中心经验
Transplant Proc. 2008 Sep;40(7):2118-20. doi: 10.1016/j.transproceed.2008.07.072.
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Recovery from established graft-vs-host disease achieved by bone marrow transplantation from a third-party allogeneic donor.通过第三方异基因供体进行骨髓移植实现已确立的移植物抗宿主病的缓解。
Exp Hematol. 2008 Sep;36(9):1216-25. doi: 10.1016/j.exphem.2008.03.018. Epub 2008 Jul 2.
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HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.采用非清髓性预处理及大剂量移植后环磷酰胺的HLA单倍型相合骨髓移植治疗血液系统恶性肿瘤
Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.