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低危骨髓增生异常综合征的当前治疗现状。

Current Therapeutic Landscape in Lower Risk Myelodysplastic Syndromes.

机构信息

Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL, USA.

Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.

出版信息

Curr Treat Options Oncol. 2023 May;24(5):387-408. doi: 10.1007/s11864-023-01062-7. Epub 2023 Mar 25.

DOI:10.1007/s11864-023-01062-7
PMID:36966266
Abstract

Lower risk myelodysplastic syndromes are typically characterized by an indolent disease course with a relatively low risk of transformation into acute myeloid leukemia. These patients are classically identified using the revised International Prognostic Scoring System and most likely its molecular version in the near future which may change the paradigm of treatment. The overall goals of care are symptomatic control to reduce transfusion requirements and improve quality of life. Symptomatic anemia is the most common indication to initiate disease-specific therapies after the optimization of supportive measures. Currently, erythropoiesis-stimulating agents remain the standard upfront therapy for anemia, and patients with del(5q) cytogenetic changes can benefit from lenalidomide monotherapy. Other therapeutic options after failure of upfront treatment include luspatercept, hypomethylating agents, and immunosuppressive therapies after taking into account of individualized disease features. Allogeneic hematopoietic stem cell transplant is the only potentially curative option and is usually reserved for medically fit patients with severe symptomatic cytopenias who failed all standard options and/or the disease is progressing toward higher risk categories. Fortunately, novel investigational therapies are rapidly emerging by targeting different biological processes contributing to MDS pathogenesis, and eligible patients should be managed in clinical trials if available.

摘要

低危骨髓增生异常综合征通常表现为疾病进程缓慢,向急性髓系白血病转化的风险相对较低。这些患者通常使用修订后的国际预后评分系统(IPSS)和近期可能改变治疗模式的其分子版本进行识别。治疗的总体目标是通过症状控制减少输血需求并提高生活质量。症状性贫血是在优化支持措施后启动针对特定疾病治疗的最常见指征。目前,红细胞生成刺激剂仍然是贫血的标准一线治疗方法,具有 del(5q)细胞遗传学改变的患者可以从来那度胺单药治疗中获益。一线治疗失败后的其他治疗选择包括芦可替尼、低甲基化剂和免疫抑制疗法,同时需要考虑个体化疾病特征。异基因造血干细胞移植是唯一潜在的治愈方法,通常保留给患有严重症状性细胞减少症且对所有标准治疗方法均无效和/或疾病进展为高危类别的身体状况良好的患者。幸运的是,通过针对导致 MDS 发病机制的不同生物学过程,新型研究性治疗方法正在迅速涌现,有资格的患者应在临床试验中进行管理(如果有)。

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本文引用的文献

1
Somatic gene mutations expose cytoplasmic DNA to co-opt the cGAS/STING/NLRP3 axis in myelodysplastic syndromes.体细胞基因突变使细胞质 DNA 暴露,从而在骨髓增生异常综合征中共同募集 cGAS/STING/NLRP3 轴。
JCI Insight. 2022 Aug 8;7(15):e159430. doi: 10.1172/jci.insight.159430.
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Myelodysplastic syndrome and autoimmune disorders: two sides of the same coin?骨髓增生异常综合征与自身免疫性疾病:同一枚硬币的两面?
Lancet Haematol. 2022 Jul;9(7):e523-e534. doi: 10.1016/S2352-3026(22)00138-7.
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Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study.
芦可替尼治疗 VEXAS 综合征比其他 JAK 抑制剂更有效:一项回顾性多中心研究。
Blood. 2022 Aug 25;140(8):927-931. doi: 10.1182/blood.2022016642.
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Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms.来那度胺可促进 TP53 突变的治疗相关髓系肿瘤的发展。
Blood. 2022 Oct 20;140(16):1753-1763. doi: 10.1182/blood.2021014956.
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TET2-Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial.TET2 驱动的克隆性造血与卡那奴单抗反应:CANTOS 随机临床试验的探索性分析。
JAMA Cardiol. 2022 May 1;7(5):521-528. doi: 10.1001/jamacardio.2022.0386.
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Targeting ineffective hematopoiesis in myelodysplastic syndromes.针对骨髓增生异常综合征中无效造血
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7
Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study.罗沙司他治疗低危骨髓增生异常综合征患者的贫血:一项 3 期研究的开放标签、剂量选择、导入阶段。
Am J Hematol. 2022 Feb 1;97(2):174-184. doi: 10.1002/ajh.26397. Epub 2021 Nov 9.
8
Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience.成功进行 VEXAS 综合征患者的异基因造血干细胞移植:来自 2 个中心的经验。
Blood Adv. 2022 Feb 8;6(3):998-1003. doi: 10.1182/bloodadvances.2021004749.
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Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry.阿扎胞苷治疗空泡酶、E1 酶、X 连锁、自身炎症、体细胞综合征(VEXAS)和骨髓增生异常综合征患者:来自法国 VEXAS 登记处的数据。
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10
Dual pyroptotic biomarkers predict erythroid response in lower-risk non-del(5q) myelodysplastic syndromes treated with lenalidomide and recombinant erythropoietin.双重焦亡生物标志物可预测接受来那度胺和重组促红细胞生成素治疗的低危非5q缺失骨髓增生异常综合征的红系反应。
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