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Rapid development of Philadelphia chromosome-negative AML in a CML patient with sustained major molecular response to tyrosine kinase inhibitor therapy.一名对酪氨酸激酶抑制剂治疗持续保持主要分子学反应的慢性粒细胞白血病患者,出现费城染色体阴性急性髓系白血病的快速进展。
Leuk Res Rep. 2025 Aug 21;24:100536. doi: 10.1016/j.lrr.2025.100536. eCollection 2025.
2
Real-world outcomes in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia treated with ponatinib - final 6-year results from a Belgian registry.接受波纳替尼治疗的费城染色体阳性急性淋巴细胞白血病或慢性粒细胞白血病患者的真实世界结局——来自比利时一项登记研究的6年最终结果
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3
Comparative Effectiveness of Newer Tyrosine Kinase Inhibitors Versus Imatinib in the First-Line Treatment of Chronic-Phase Chronic Myeloid Leukemia Across Risk Groups: A Systematic Review and Meta-Analysis of Eight Randomized Trials.新型酪氨酸激酶抑制剂与伊马替尼在不同风险组慢性期慢性髓性白血病一线治疗中的疗效比较:八项随机试验的系统评价和荟萃分析
Clin Lymphoma Myeloma Leuk. 2016 Jun;16(6):e85-94. doi: 10.1016/j.clml.2016.03.003. Epub 2016 Mar 30.
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Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses.达沙替尼、尼洛替尼和标准剂量伊马替尼一线治疗慢性髓性白血病:系统评价和经济分析。
Health Technol Assess. 2012;16(42):iii-iv, 1-277. doi: 10.3310/hta16420.
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Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature.慢性髓性白血病中涉及 BCR::ABL1 的复杂易位是否会影响酪氨酸激酶抑制剂的反应率?系统文献回顾。
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Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: a case study for technology appraisal on the basis of surrogate outcomes evidence.在慢性髓性白血病一线治疗中,完全细胞遗传学缓解和主要分子学缓解作为总生存的替代终点:基于替代终点证据的技术评估案例研究。
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本文引用的文献

1
Development of Philadelphia chromosome-negative acute myeloid leukemia with IDH2 and NPM1 mutations in a patient with chronic myeloid leukemia who showed a major molecular response to tyrosine kinase inhibitor therapy.慢性髓性白血病患者酪氨酸激酶抑制剂治疗后达到主要分子学缓解,继而发生伴有 IDH2 和 NPM1 突变的费城染色体阴性急性髓系白血病。
Int J Hematol. 2021 Jun;113(6):936-940. doi: 10.1007/s12185-020-03074-7. Epub 2021 Jan 5.
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[Philadelphia chromosome-negative myeloid neoplasms in patients with Philadelphia chromosome-positive chronic myeloid leukemia during tyrosine kinase inhibtor-therapy].[酪氨酸激酶抑制剂治疗期间费城染色体阳性慢性髓性白血病患者中的费城染色体阴性髓系肿瘤]
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3
Clinical implications of clonal chromosomal abnormalities in Philadelphia negative cells in CML patients after treated with tyrosine kinase inhibitors.慢性粒细胞白血病患者经酪氨酸激酶抑制剂治疗后费城阴性细胞中克隆性染色体异常的临床意义
Cancer Genet. 2019 Oct;238:44-49. doi: 10.1016/j.cancergen.2019.07.008. Epub 2019 Jul 24.
4
Clonal chromosomal aberrations in Philadelphia negative cells such as monosomy 7 and trisomy 8 may persist for years with no impact on the long term outcome in patients with chronic myeloid leukemia.费城阴性细胞中的克隆性染色体畸变,如7号染色体单体和8号染色体三体,可能会持续数年,而对慢性髓性白血病患者的长期预后没有影响。
Cancer Genet. 2017 Oct;216-217:1-9. doi: 10.1016/j.cancergen.2017.04.066. Epub 2017 Apr 28.
5
Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment.慢性粒细胞白血病治疗期间出现在费城染色体阴性中期的克隆性染色体异常。
Blood. 2017 Nov 9;130(19):2084-2091. doi: 10.1182/blood-2017-07-792143. Epub 2017 Aug 23.
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Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia.伊马替尼治疗慢性髓性白血病的长期疗效
N Engl J Med. 2017 Mar 9;376(10):917-927. doi: 10.1056/NEJMoa1609324.
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European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013.欧洲白血病网络关于慢性髓性白血病管理的建议:2013 年版。
Blood. 2013 Aug 8;122(6):872-84. doi: 10.1182/blood-2013-05-501569. Epub 2013 Jun 26.
8
Myelodysplastic syndrome with Ph negative monosomy 7 chromosome following transient bone marrow dysplasia during imatinib treatment for chronic myeloid leukemia.慢性髓性白血病伊马替尼治疗期间短暂性骨髓发育异常后出现的伴有Ph阴性7号染色体单体的骨髓增生异常综合征
Intern Med. 2011;50(5):481-5. doi: 10.2169/internalmedicine.50.4481. Epub 2011 Mar 1.
9
The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells.费城染色体阴性细胞中存在克隆性细胞遗传学异常的慢性髓性白血病患者的预后。
Cancer. 2007 Oct 1;110(7):1509-19. doi: 10.1002/cncr.22936.
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Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate therapy for chronic myeloid leukemia.慢性粒细胞白血病接受甲磺酸伊马替尼治疗后发生的骨髓增生异常综合征和急性白血病。
Blood. 2006 Oct 15;108(8):2811-3. doi: 10.1182/blood-2006-04-017400. Epub 2006 Jun 29.

一名对酪氨酸激酶抑制剂治疗持续保持主要分子学反应的慢性粒细胞白血病患者,出现费城染色体阴性急性髓系白血病的快速进展。

Rapid development of Philadelphia chromosome-negative AML in a CML patient with sustained major molecular response to tyrosine kinase inhibitor therapy.

作者信息

Liu Huan, Sun Yunxia, Li Liangliang, Zhang Yurong, Zhou Yaxiong, Zeng Pengyun, Yue Lingling

机构信息

Department of Hematology, The Second Hospital & Clinical Medical School, Lanzhou University, No. 82, Cuyingmen, Lanzhou, Gansu Province 730030, China.

Department of Hematology, The First People's Hospital of Lanzhou, China.

出版信息

Leuk Res Rep. 2025 Aug 21;24:100536. doi: 10.1016/j.lrr.2025.100536. eCollection 2025.

DOI:10.1016/j.lrr.2025.100536
PMID:40917154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12409312/
Abstract

The use of TKIs has significantly improved the prognosis of CML. However, a small subset of patients still experience poor outcomes. We present a rare case of Ph-AML following a diagnosis of CML. The patient achieved CCyR and MMR after 4 months of nilotinib therapy, with sustained deep remission for 3 years. Unexpectedly, the disease developed rapidly to AML. Further investigations revealed the emergence of CCA/Ph- and gene mutations. We retrospectively analyzed previous CML patients with and Ph-negative status in blast crisis from our database and conducted a comprehensive review of the relevant literature.

摘要

酪氨酸激酶抑制剂(TKIs)的使用显著改善了慢性粒细胞白血病(CML)的预后。然而,一小部分患者的预后仍然较差。我们报告了一例诊断为CML后发生Ph阴性急性髓系白血病(Ph-AML)的罕见病例。患者在接受尼洛替尼治疗4个月后达到完全细胞遗传学缓解(CCyR)和主要分子学缓解(MMR),并持续深度缓解3年。出乎意料的是,疾病迅速发展为AML。进一步检查发现了CCA/Ph-和基因突变的出现。我们回顾性分析了我们数据库中既往处于急变期且具有和Ph阴性状态的CML患者,并对相关文献进行了全面综述。