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异基因造血细胞移植与细胞治疗

英文原题:Allogeneic Hematopoietic Cell Transplantation and Cellular Therapy.

查看英文原题

Allogeneic Hematopoietic Cell Transplantation and Cellular Therapy.

PubMed 2021/10/14(内容时间) Blood Cell Ther

研究概要

急性髓系白血病(AML)和骨髓增生异常综合征(MDS)患者通常需要异基因造血细胞移植(allo-HCT)才能治愈,但核心结合因子AML等具有良好遗传基因型的患者除外。

中文摘要

除核心结合因子AML等具有有利遗传基因型的患者外,急性髓系白血病(AML)和骨髓增生异常综合征(MDS)患者通常需要异基因造血细胞移植(allo-HCT)才能治愈。然而,强化化疗后及时进行HCT仍不能完全避免疾病复发或难治。尽管移植技术和并发症管理已有改善,仍亟需进一步提高HCT结局。此外,谨慎的患者咨询、供者选择和移植类型决策,对于最大限度发挥早期异基因移植的获益至关重要。目前正在积极研究HCT后维持治疗,重点是选择性免疫调节联合靶向免疫疗法,以控制持续存在或复发的血液系统恶性肿瘤。为改善移植物抗宿主病(GVHD)、复发和感染之间的平衡,研究者探索了纯化血干细胞移植物联合体外扩增的供者T细胞;这些T细胞靶向常见感染和白血病抗原。针对感染因子的T细胞还可从冷冻细胞库中获得HLA部分匹配的第三方T细胞。多项研究证实,供者来源CMV和EBV特异性T细胞具有临床价值。这一方法也已用于急性白血病;目前正在开展的试验包括allo-HCT后输注供者来源、靶向多种白血病抗原(如WT1、PRAME、survivin和NY-ESO)的细胞毒性T细胞,以及供者来源CAR19 T细胞。

展开英文摘要原文

Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) generally require allogeneic hematopoietic cell transplantation (allo-HCT) for a cure, except for patients with favorable genetic genotypes such as those with core-binding factor AML. However, the use of intensive chemotherapy followed by prompt HCT does not fully prevent relapse or refractory disease. Despite improvements in transplant techniques and management of complications, further improvement of HCT outcomes is urgently needed. Moreover, careful patient counseling, donor selection, and choice of transplant type are essential to maximize the benefits of early allografting. Maintenance after HCT focusing on selective immunomodulation combined with targeted immunotherapies that control persisting or relapsed hematologic malignancies is currently under active investigation. To improve the balance between GVHD, relapse, and infection, the use of purified blood stem cell grafts in conjunction with ex vivo expanded T-cells from stem cell donors targeting common infectious and leukemic antigens has been explored. T cells against infectious agents might also be generated using partially HLA-matched third-party T cells from cryopreserved cell banks, and a series of studies confirmed the clinical value of donor-derived CMV- and EBV-specific T cells. This approach has also been applied to acute leukemia, and trials using donor-derived cytotoxic T-cells targeting multiple leukemic antigens such as WT1 , PRAME , survivin , and NY-ESO , as well as donor-derived CAR19 T-cells after allo-HCT, are currently underway.

论文信息

作者
Kim HJ、Weisdorf D、Gottlieb DJ
第一作者单位
Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, the Republic of Korea.South Korea
通讯作者单位
Westmead Hospital University of Sydney, Sydney, Australia.Australia
期刊
Blood cell therapy2021 Oct 14
原文标识
PubMed 36713469 · DOI 10.31547/bct-2021-014