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供体白细胞输注后的移植物抗骨髓瘤效应:骨髓缓解得以维持,但出现浆细胞瘤导致髓外复发。

Graft-versus-myeloma after donor leukocyte infusion: maintenance of marrow remission but extramedullary relapse with plasmacytomas.

作者信息

Zomas A, Stefanoudaki K, Fisfis M, Papadaki T, Mehta J

机构信息

Hematology Department, St Anargyri General Cancer Hospital, Athens, Greece.

出版信息

Bone Marrow Transplant. 1998 Jun;21(11):1163-5. doi: 10.1038/sj.bmt.1701236.

DOI:10.1038/sj.bmt.1701236
PMID:9645583
Abstract

Adoptive immunotherapy with donor leukocytes has emerged as a promising strategy for the treatment of myeloma recurrence after allogeneic transplantation. 2.9 x 10(8)/kg donor mononuclear cells containing 1.4% CD34+ and 37% CD3+ cells were administered to a 48-year-old patient with non-secretory plasmablastic myeloma relapsing 9 months after a blood stem cell transplant from his HLA-identical sibling. In view of the extensive marrow infiltration and the aggressive behaviour of the disease, the donor cells were preceded by a course of EDAP chemotherapy. There was rapid clinical improvement, and CR was achieved on day 30 post infusion. However, three subcutaneous plasmacytomas showing anaplastic features developed within a few days. These failed to respond to interferon-alpha and continued to grow for 5 weeks in the absence of marrow plasmacytosis or other evidence of systemic disease. Grade 3 acute liver GVHD developed on day 79 which was controlled with immunosuppression. Overt systemic relapse occurred on day 90 as the GVHD came under control. The course of our case suggests highly proliferative malignant cells may escape the graft-versus-tumour effect of immunocompetent allogeneic cells in extramedullary sites subsequently resulting in overt systemic relapse if left untreated. New approaches are needed to deal with the problem of extramedullary disease recurrence.

摘要

采用供体白细胞进行过继性免疫治疗已成为治疗异基因移植后骨髓瘤复发的一种有前景的策略。将含有1.4% CD34+和37% CD3+细胞的2.9×10(8)/kg供体单个核细胞给予一名48岁的非分泌型浆母细胞骨髓瘤患者,该患者在接受来自其 HLA 相同同胞的造血干细胞移植9个月后复发。鉴于广泛的骨髓浸润和疾病的侵袭性,在输注供体细胞之前先进行了一个疗程的 EDAP 化疗。临床迅速改善,输注后第30天达到完全缓解。然而,几天内出现了3个表现为间变特征的皮下浆细胞瘤。这些瘤对α干扰素无反应,在无骨髓浆细胞增多或其他全身疾病证据的情况下持续生长5周。79天时发生3级急性肝移植物抗宿主病(GVHD),通过免疫抑制得以控制。当 GVHD 得到控制时,90天时出现明显的全身复发。我们这个病例的病程提示,高度增殖的恶性细胞可能逃避免疫活性异基因细胞在髓外部位的移植物抗肿瘤效应,随后如果不进行治疗,会导致明显的全身复发。需要新的方法来处理髓外疾病复发的问题。

相似文献

1
Graft-versus-myeloma after donor leukocyte infusion: maintenance of marrow remission but extramedullary relapse with plasmacytomas.供体白细胞输注后的移植物抗骨髓瘤效应:骨髓缓解得以维持,但出现浆细胞瘤导致髓外复发。
Bone Marrow Transplant. 1998 Jun;21(11):1163-5. doi: 10.1038/sj.bmt.1701236.
2
Donor leukocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual donor T cells.异基因骨髓移植后复发性血液系统恶性肿瘤的供体白细胞输注:输注的和残留的供体T细胞的影响
Bone Marrow Transplant. 1998 Dec;22(11):1057-63. doi: 10.1038/sj.bmt.1701496.
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Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.异基因反应性作为血液系统恶性肿瘤治疗的治疗原则。非清髓性预处理的异基因造血细胞移植的临床和免疫学方面的研究。
Dan Med Bull. 2007 May;54(2):112-39.
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Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease.α干扰素联合极低剂量供体淋巴细胞输注治疗慢性髓性白血病血液学或细胞遗传学复发可诱导快速且持久的完全缓解,并与可接受的移植物抗宿主病相关。
Biol Blood Marrow Transplant. 2004 Mar;10(3):204-12. doi: 10.1016/j.bbmt.2003.11.003.
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Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma.改良预处理方案白消安-环磷酰胺序贯异基因干细胞移植治疗多发性骨髓瘤患者
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Discrepancy between serological complete remission and concomitant new bone lytic lesions after infusion of escalating low doses of donor lymphocytes in multiple myeloma: a case report.多发性骨髓瘤患者输注递增低剂量供体淋巴细胞后血清学完全缓解与同时出现新的骨溶解性病变之间的差异:一例报告
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[Donor peripheral hematopoietic stem cells infusion for prophylaxis of relapse of high risk leukemia after allogeneic hematopoietic stem cell transplantation].
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Chemotherapy does not nullify the ability of donor lymphocyte infusions to mediate graft-versus-host reactions.化疗不会消除供体淋巴细胞输注介导移植物抗宿主反应的能力。
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Donor leukocyte infusions inducing remissions repeatedly in a patient with recurrent multiple myeloma after allogeneic bone marrow transplantation.供体白细胞输注使一名异基因骨髓移植后复发性多发性骨髓瘤患者多次缓解。
Bone Marrow Transplant. 1999 Jan;23(2):195-7. doi: 10.1038/sj.bmt.1701546.
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A trend towards an increased incidence of chronic graft-versus-host disease following allogeneic peripheral blood progenitor cell transplantation: a case controlled study.异基因外周血祖细胞移植后慢性移植物抗宿主病发病率增加的趋势:一项病例对照研究。
Bone Marrow Transplant. 1998 Aug;22(3):273-6. doi: 10.1038/sj.bmt.1701327.

引用本文的文献

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Isolated orbital relapse of multiple myeloma in a patient with severe chronic GVHD after allogeneic hematopoietic SCT.异基因造血干细胞移植后发生严重慢性移植物抗宿主病的患者出现孤立性眼眶多发性骨髓瘤复发。
Bone Marrow Transplant. 2014 Jul;49(7):988-9. doi: 10.1038/bmt.2014.81. Epub 2014 Apr 28.
2
Immune escape from NY-ESO-1-specific T-cell therapy via loss of heterozygosity in the MHC.通过 MHC 杂合性丢失实现针对 NY-ESO-1 的 T 细胞免疫逃逸。
Gene Ther. 2014 Mar;21(3):337-42. doi: 10.1038/gt.2013.87. Epub 2014 Jan 23.