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欧洲白血病网络(ELN)治疗慢性粒细胞白血病的新建议

The New ELN Recommendations for Treating CML.

作者信息

Hehlmann Rüdiger

机构信息

ELN-Foundation, Weinheim and Medical Faculty Mannheim of Heidelberg University, 69126 Mannheim, Germany.

出版信息

J Clin Med. 2020 Nov 16;9(11):3671. doi: 10.3390/jcm9113671.

Abstract

After normal survival has been achieved in most patients with chronic myeloid leukemia (CML), a new goal for treating CML is survival at good quality of life, with treatment discontinuation in sustained deep molecular response (DMR; MR or deeper) and treatment-free remission (TFR). Four tyrosine kinase inhibitors (TKIs) have been approved for first-line therapy: imatinib, dasatinib, nilotinib, bosutinib. Unexpectedly, the outcome of long-term randomized trials has shown that faster response as achieved by higher doses of imatinib, imatinib in combination, or second-generation (2G)-TKIs, does not translate into a survival advantage. Serious and frequent, and in part cumulative long-term toxicities, have led to a reevaluation of the role of 2G-TKIs in first-line therapy. Generic imatinib is the current most cost-effective first-line therapy in the chronic phase. A change of treatment is recommended when intolerance cannot be ameliorated or molecular milestones are not reached. Patient comorbidities and contraindications of all TKIs must be considered. Risk profile at diagnosis should be assessed with the EUTOS score for long-term survival (ELTS). Monitoring of response is by polymerase chain reaction (PCR). Cytogenetics is still required in the case of atypical translocations, atypical transcripts, and additional chromosomal aberrations. TKIs are contraindicated during pregnancy. Since the majority of patients are at risk of lifelong exposure to TKIs, amelioration of chronic low-grade side effects is important.

摘要

在大多数慢性髓性白血病(CML)患者实现正常生存后,治疗CML的新目标是实现高质量生活下的生存,在持续深度分子反应(DMR;MR或更深)和无治疗缓解(TFR)状态下停止治疗。四种酪氨酸激酶抑制剂(TKIs)已被批准用于一线治疗:伊马替尼、达沙替尼、尼洛替尼、博舒替尼。出乎意料的是,长期随机试验结果表明,高剂量伊马替尼、伊马替尼联合用药或第二代(2G)-TKIs所实现的更快反应并未转化为生存优势。严重且频繁,部分具有累积性的长期毒性,促使人们重新评估2G-TKIs在一线治疗中的作用。通用型伊马替尼是目前慢性期最具成本效益的一线治疗药物。当不耐受无法改善或未达到分子里程碑时,建议更换治疗方案。必须考虑患者的合并症以及所有TKIs的禁忌症。诊断时的风险概况应通过欧洲白血病网络长期生存(ELTS)评分进行评估。通过聚合酶链反应(PCR)监测反应情况。对于非典型易位、非典型转录本和额外染色体畸变的情况,仍需要进行细胞遗传学检查。孕期禁用TKIs。由于大多数患者有终身暴露于TKIs的风险,改善慢性低度副作用很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef6f/7697560/dbbca7434a95/jcm-09-03671-g001.jpg

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