- 突变型急性髓系白血病的维持治疗。
Maintenance therapy for -mutated acute myeloid leukemia.
机构信息
Department of Internal Medicine, Hematology, Oncology and Immunology, Philipps University Marburg and University Hospital Giessen and Marburg, Campus Marburg, Marburg.
出版信息
Haematologica. 2021 Mar 1;106(3):664-670. doi: 10.3324/haematol.2019.240747.
Abstract
FLT3-ITD is a constitutively activated variant of the FLT3 tyrosine kinase receptor. Its expression in acute myeloid leukemia (AML) is associated with a poor prognosis. Due to this, the development of tyrosine kinase inhibitors (TKI) blocking FLT3-ITD became a rational therapeutic concept. This review describes key milestones in the clinical development of different FLT3-specific TKI with a particular focus on FLT3-TKI maintenance therapy in remission after allogeneic hematopoietic stem cell transplantation (HCT). Recent evidence from randomized trials using sorafenib in FLT3-ITD mutated AML provided a proof of concept that targeted post-HCT maintenance therapy could become a new treatment paradigm in AML.
摘要
FLT3-ITD 是 FLT3 酪氨酸激酶受体的组成性激活变体。其在急性髓系白血病（AML）中的表达与预后不良相关。因此，开发阻断 FLT3-ITD 的酪氨酸激酶抑制剂（TKI）成为一种合理的治疗概念。本综述描述了不同 FLT3 特异性 TKI 临床开发的关键里程碑，特别关注异基因造血干细胞移植（HCT）后缓解期的 FLT3-TKI 维持治疗。最近使用索拉非尼治疗 FLT3-ITD 突变 AML 的随机试验提供了证据，证明针对移植后维持治疗可能成为 AML 的一种新治疗模式。
相似文献
1
Maintenance therapy for -mutated acute myeloid leukemia.- 突变型急性髓系白血病的维持治疗。
Haematologica. 2021 Mar 1;106(3):664-670. doi: 10.3324/haematol.2019.240747.
2
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With -Internal Tandem Duplication Mutation (SORMAIN).异基因造血干细胞移植治疗伴有内部串联重复突变的急性髓系白血病后的索拉非尼维持治疗（SORMAIN）。
J Clin Oncol. 2020 Sep 10;38(26):2993-3002. doi: 10.1200/JCO.19.03345. Epub 2020 Jul 16.
3
Sorafenib Maintenance Appears Safe and Improves Clinical Outcomes in FLT3-ITD Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation.索拉非尼维持治疗在异基因造血细胞移植后的FLT3-ITD急性髓系白血病中似乎安全且能改善临床结局。
Clin Lymphoma Myeloma Leuk. 2015 May;15(5):298-302. doi: 10.1016/j.clml.2014.12.005. Epub 2014 Dec 12.
4
Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission.在首次完全缓解的FLT3-ITD急性髓系白血病患者中进行有或没有索拉非尼维持治疗的造血细胞移植。
Br J Haematol. 2016 Nov;175(3):496-504. doi: 10.1111/bjh.14260. Epub 2016 Jul 19.
5
Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment.FLT3-ITD阳性急性髓系白血病的预后：异基因干细胞移植和酪氨酸激酶抑制剂治疗的影响
J Cancer Res Clin Oncol. 2017 Feb;143(2):337-345. doi: 10.1007/s00432-016-2290-5. Epub 2016 Oct 24.
6
Efficacy and Feasibility of Sorafenib as a Maintenance Agent After Allogeneic Hematopoietic Stem Cell Transplantation for Fms-like Tyrosine Kinase 3 Mutated Acute Myeloid Leukemia: An Update.索拉非尼作为 Fms 样酪氨酸激酶 3 突变型急性髓系白血病异基因造血干细胞移植后维持治疗药物的疗效和可行性：更新。
Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):506-508. doi: 10.1016/j.clml.2019.04.004. Epub 2019 Apr 18.
7
Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation.索拉非尼对接受异基因造血干细胞移植的伴有 FLT3-ITD 急性髓系白血病患者结局的影响。
Cancer. 2018 May 1;124(9):1954-1963. doi: 10.1002/cncr.31295. Epub 2018 Mar 6.
8
TKI Maintenance After Stem-Cell Transplantation for -ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.TKI 维持治疗对伴有 ITD 阳性的急性髓系白血病患者干细胞移植后的疗效：一项系统性评价和荟萃分析。
Front Immunol. 2021 Mar 12;12:630429. doi: 10.3389/fimmu.2021.630429. eCollection 2021.
9
Treatment of FLT3-ITD-positive acute myeloid leukemia relapsing after allogeneic stem cell transplantation with sorafenib.索拉非尼治疗异基因造血干细胞移植后复发的 FLT3-ITD 阳性急性髓系白血病。
Biol Blood Marrow Transplant. 2011 Dec;17(12):1874-7. doi: 10.1016/j.bbmt.2011.07.011. Epub 2011 Jul 20.
10
Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial.索拉非尼维持治疗伴 FLT3-ITD 急性髓系白血病行异基因造血干细胞移植患者：一项开放标签、多中心、随机 3 期临床试验。
Lancet Oncol. 2020 Sep;21(9):1201-1212. doi: 10.1016/S1470-2045(20)30455-1. Epub 2020 Aug 10.
引用本文的文献
1
Incidence and prognostic factors for pulmonary infection complications in elderly patients with acute myeloid leukemia.老年急性髓系白血病患者肺部感染并发症的发生率及预后因素
Am J Transl Res. 2025 Jul 15;17(7):5371-5384. doi: 10.62347/KERT9218. eCollection 2025.
2
Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.嵌合抗原受体T细胞疗法治疗急性髓系白血病的最新进展
Front Immunol. 2025 May 2;16:1572407. doi: 10.3389/fimmu.2025.1572407. eCollection 2025.
3
Tyrosine kinase inhibitor maintenance therapy after stem cell transplantation for FLT3-mutated acute myeloid leukemia.FLT3突变型急性髓系白血病干细胞移植后的酪氨酸激酶抑制剂维持治疗。
Cochrane Database Syst Rev. 2025 Apr 28;4(4):CD016090. doi: 10.1002/14651858.CD016090.
4
Revisiting the Role of Long Non-coding RNA PSMA3-AS1 in Human Cancers: Current Evidence and Future Directions.重新审视长链非编码RNA PSMA3-AS1在人类癌症中的作用：当前证据与未来方向
Curr Pharm Des. 2025;31(21):1683-1695. doi: 10.2174/0113816128350406241223053744.
5
Unveiling unexpected adverse events: post-marketing safety surveillance of gilteritinib and midostaurin from the FDA Adverse Event Reporting database.揭示意外不良事件：来自美国食品药品监督管理局不良事件报告数据库的吉列替尼和米哚妥林的上市后安全性监测
Ther Adv Drug Saf. 2025 Jan 10;16:20420986241308089. doi: 10.1177/20420986241308089. eCollection 2025.
6
RNF38 promotes gilteritinib resistance in acute myeloid leukemia via inducing autophagy by regulating ubiquitination of LMX1A.RNF38 通过调节 LMX1A 的泛素化诱导自噬促进急性髓系白血病对吉特替尼的耐药性。
Cell Biol Toxicol. 2024 Nov 28;40(1):105. doi: 10.1007/s10565-024-09936-8.
7
Immunoediting in acute myeloid leukemia: Reappraising T cell exhaustion and the aberrant antigen processing machinery in leukemogenesis.急性髓系白血病中的免疫编辑：重新评估白血病发生中的T细胞耗竭及异常抗原加工机制。
Heliyon. 2024 Oct 25;10(21):e39731. doi: 10.1016/j.heliyon.2024.e39731. eCollection 2024 Nov 15.
8
Outcomes with intensive treatment for acute myeloid leukemia: an analysis of two decades of data from the HARMONY Alliance.急性髓系白血病强化治疗的结果：对来自HARMONY联盟二十年数据的分析
Haematologica. 2025 May 1;110(5):1126-1140. doi: 10.3324/haematol.2024.285805. Epub 2024 Nov 7.
9
Long-term remissions with Gilteritinib in early relapse after allogeneic stem cell transplantation of FLT3/NPM1 mutated acute myeloid leukemia.吉瑞替尼治疗FLT3/NPM1突变型急性髓系白血病异基因干细胞移植后早期复发的长期缓解情况。
Blood Cell Ther. 2024 Jun 14;7(3):75-78. doi: 10.31547/bct-2024-005. eCollection 2024 Aug 25.
10
Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.癌症干细胞中的脂质代谢动态：癌症的潜在靶点。
Front Pharmacol. 2024 Jun 27;15:1367981. doi: 10.3389/fphar.2024.1367981. eCollection 2024.
本文引用的文献
1
Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia.异基因造血干细胞移植后米哚妥林治疗 FLT3 内部串联重复阳性急性髓系白血病。
Bone Marrow Transplant. 2021 May;56(5):1180-1189. doi: 10.1038/s41409-020-01153-1. Epub 2020 Dec 7.
2
Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial.rhG-CSF 联合地西他滨预防高危 MRD 阴性 AML 患者 HSCT 后复发的疗效：一项开放标签、多中心、随机对照试验。
J Clin Oncol. 2020 Dec 20;38(36):4249-4259. doi: 10.1200/JCO.19.03277. Epub 2020 Oct 27.
3
Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial.索拉非尼维持治疗伴 FLT3-ITD 急性髓系白血病行异基因造血干细胞移植患者：一项开放标签、多中心、随机 3 期临床试验。
Lancet Oncol. 2020 Sep;21(9):1201-1212. doi: 10.1016/S1470-2045(20)30455-1. Epub 2020 Aug 10.
4
Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia.阿扎胞苷和维奈托克治疗未经治急性髓系白血病。
N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971.
5
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With -Internal Tandem Duplication Mutation (SORMAIN).异基因造血干细胞移植治疗伴有内部串联重复突变的急性髓系白血病后的索拉非尼维持治疗（SORMAIN）。
J Clin Oncol. 2020 Sep 10;38(26):2993-3002. doi: 10.1200/JCO.19.03345. Epub 2020 Jul 16.
6
FLT3 inhibitors added to induction therapy induce deeper remissions.在诱导治疗中添加FLT3抑制剂可诱导更深的缓解。
Blood. 2020 Jan 2;135(1):75-78. doi: 10.1182/blood.2019002180.
7
Gilteritinib or Chemotherapy for Relapsed or Refractory -Mutated AML.吉特替尼与化疗用于治疗复发/难治性 - 突变型 AML。
N Engl J Med. 2019 Oct 31;381(18):1728-1740. doi: 10.1056/NEJMoa1902688.
8
Factors Associated With Successful Discontinuation of Immune Suppression After Allogeneic Hematopoietic Cell Transplantation.异基因造血细胞移植后免疫抑制成功停药的相关因素。
JAMA Oncol. 2020 Jan 1;6(1):e192974. doi: 10.1001/jamaoncol.2019.2974. Epub 2020 Jan 9.
9
Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial.Quizartinib 与挽救性化疗治疗复发或难治性 FLT3-ITD 急性髓系白血病（QuANTUM-R）：一项多中心、随机、对照、开放标签、3 期临床试验。
Lancet Oncol. 2019 Jul;20(7):984-997. doi: 10.1016/S1470-2045(19)30150-0. Epub 2019 Jun 4.
10
Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients.强化化疗后阿扎胞苷维持治疗可改善老年 AML 患者的DFS。
Blood. 2019 Mar 28;133(13):1457-1464. doi: 10.1182/blood-2018-10-879866. Epub 2019 Jan 10.
Zotero 插件