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异基因造血干细胞移植治疗 MDS 或 AML 的通科医生:表观遗传学治疗。

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy.

机构信息

Medical Center of Hematology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China.

出版信息

Front Immunol. 2022 Oct 4;13:1034438. doi: 10.3389/fimmu.2022.1034438. eCollection 2022.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for patients with myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse and graft-versus-host disease (GvHD) still affect the survival of patients who receive allo-HSCT, and more appropriate therapeutic strategies should be applied at all stages of transplantation to prevent these adverse events. The use of epigenetics agents, such as hypomethylating agents (HMAs), has been explored to decrease the risk of relapse by epigenetic modulation, which is especially effective among AML patients with poor mutations in epigenetic regulators. Furthermore, epigenetic agents have also been regarded as prophylactic methods for GvHD management without abrogating graft versus leukemia (GvL) effects. Therefore, the combination of epigenetic therapy and HSCT may optimize the transplantation process and prevent treatment failure. Existing studies have investigated the feasibility and effectiveness of using HMAs in the pretransplant, transplant and posttransplant stages among MDS and AML patients. This review examines the application of HMAs as a bridge treatment to reduce the tumor burden and the determine appropriate dose during allo-HSCT. Within this review, we also examine the efficacy and safety of HMAs alone or HMA-based strategies in posttransplant settings for MDS and AML. Finally, we provide an overview of other epigenetic candidates, which have been discussed in the nontransplant setting.

摘要

异基因造血干细胞移植(allo-HSCT)仍然是治疗骨髓增生异常综合征(MDS)和急性髓系白血病(AML)等髓系恶性肿瘤患者的唯一治愈方法。然而,移植后复发和移植物抗宿主病(GvHD)仍然影响接受 allo-HSCT 患者的生存,应该在移植的所有阶段应用更合适的治疗策略来预防这些不良事件。已经探索了使用表观遗传学药物(如低甲基化剂(HMAs))来降低复发风险的方法,通过表观遗传学调节,这在表观遗传学调节剂中存在不良突变的 AML 患者中尤其有效。此外,表观遗传学药物也被认为是预防 GvHD 管理的方法,而不会削弱移植物抗白血病(GvL)的效果。因此,表观遗传学治疗与 HSCT 的联合可能优化移植过程并预防治疗失败。现有的研究已经探讨了在 MDS 和 AML 患者的移植前、移植中和移植后阶段使用 HMAs 的可行性和有效性。本综述检查了 HMAs 作为桥梁治疗在 allo-HSCT 期间降低肿瘤负担和确定适当剂量的应用。在本综述中,我们还检查了 HMAs 单独或基于 HMA 的策略在 MDS 和 AML 移植后环境中的疗效和安全性。最后,我们概述了在非移植环境中讨论的其他表观遗传候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bfc/9577610/abb54b978b64/fimmu-13-1034438-g001.jpg

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