Slezáková Katarína, Mistrík Martin, Bátorová Angelika
Vnitr Lek. 2020 Summer;66(4):214-224.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia that is characterised by Philadelphia chromosome (Ph1 chromosome) and/or fusion gene BCR-ABL1 in bone marrow. Interpheron α and bone marrow transplantation used to be the main treatment modalities for patients with CML 20 years ago. Due to the introduction of imatinib mesylate since the year 2000 the outcome of CML patients has dramatically improved. The survival of both younger and elderly patients in the case of an optimal response has been prolonged and currently is close to survival of healthy population. Although, one third of patients does not respond well to first line imatinib and needs to change the treatment to second line tyrosine kinase inhibitors (TKI: bosutinib, dasatinib and nilotinib). Younger patients without cardiologic and metabolic disorders and those with poor risk profile score may have benefit from TKI of 2nd generation as a 1st line treatment option with the aim of reaching deeper molecular response and the chance of treatment free remission (TFR) in future. By older patients with severe comorbidities and in patients with good risk profile score imatinib as a 1st line treatment option can be used. For patients who are resistant simultaneously to 2nd generation TKI and for patients with mutation T315I ponatinib - TKI of 3rd generation can be used effectively. Intolerance and toxicity of TKI´s are the main barriers of effective CML treatment. TKI selection for each patient should be individual. Patient´s cooperation with medical team is crucial and inevitable in long time treatment process. The chance for TFR has become feasible for approximately 40-60 % CML patients in deep and durable molecular remission and represents a further important milestone in the management of CML patients.
慢性髓性白血病(CML)是一种克隆性骨髓增殖性肿瘤,其特征是骨髓中存在费城染色体(Ph1染色体)和/或融合基因BCR-ABL1。20年前,干扰素α和骨髓移植曾是CML患者的主要治疗方式。自2000年引入甲磺酸伊马替尼以来,CML患者的治疗效果有了显著改善。在获得最佳反应的情况下,年轻和老年患者的生存期均得以延长,目前已接近健康人群的生存期。尽管如此,三分之一的患者对一线伊马替尼反应不佳,需要更换为二线酪氨酸激酶抑制剂(TKI:博舒替尼、达沙替尼和尼洛替尼)。没有心脏和代谢疾病且风险特征评分较差的年轻患者,可能会从第二代TKI作为一线治疗方案中获益,目的是实现更深的分子反应以及未来无治疗缓解(TFR)的机会。对于患有严重合并症的老年患者以及风险特征评分良好的患者,可以使用伊马替尼作为一线治疗方案。对于同时对第二代TKI耐药的患者以及存在T315I突变的患者,可以有效使用第三代TKI泊那替尼。TKI的不耐受性和毒性是CML有效治疗的主要障碍。为每位患者选择TKI应因人而异。在长期治疗过程中,患者与医疗团队的合作至关重要且不可或缺。对于大约40%-60%处于深度和持久分子缓解状态的CML患者来说,TFR已成为可能,这代表了CML患者管理中的又一个重要里程碑。