Lahaye Tanja, Riehm Birte, Berger Ute, Paschka Peter, Müller Martin C, Kreil Sebastian, Merx Kirsten, Schwindel Uwe, Schoch Claudia, Hehlmann Rüdiger, Hochhaus Andreas
III. Medizinische Klinik Mannheim der Universität Heidelberg, Mannheim, Germany.
Cancer. 2005 Apr 15;103(8):1659-69. doi: 10.1002/cncr.20922.
The advent of imatinib has considerably changed the treatment of chronic myeloid leukemia (CML). Early studies demonstrated high rates of hematologic and cytogenetic responses in all phases of the disease after limited observation periods.
The authors evaluated long-term outcome, rates of response, and resistance in 300 patients with BCR-ABL-positive leukemias (CML in chronic phase after failure to respond to interferon-alpha [CP], n = 139; accelerated phase [AP], n = 80; myeloid blast crisis [BC], n = 76; lymphoid BC and Philadelphia chromosome-positive acute lymphoblastic leukemia, n = 5) who entered clinical trials with imatinib in a single center after an observation time of 4.5 years.
In CP, hematologic remission was achieved in 97% and major (MCR) and complete cytogenetic remission (CCR) in 61% and 49% of patients, respectively. The chance to achieve MCR was higher in patients commencing imatinib earlier in the course of CML. In AP, the median survival period after the start of imatinib was 44 months, and MCR and CCR were observed in 31% and 26% of patients, respectively. In myeloid BC, the median survival period after the start of imatinib and after diagnosis of BC was 6 and 9 months, respectively. Hematologic resistance occurred in 25%, 41%, and 92% of patients in CP, AP, and myeloid BC, respectively, and was associated with BCR-ABL mutations in 45% of patients and with clonal evolution in 58% of patients.
The data emphasized the need for a prolonged follow-up of patients treated with imatinib to define the clinical potential of the drug and to establish methods to optimize therapy.
伊马替尼的出现显著改变了慢性髓性白血病（CML）的治疗方式。早期研究表明，在有限的观察期后，该疾病各阶段的血液学和细胞遗传学缓解率都很高。
作者评估了300例BCR-ABL阳性白血病患者（对α干扰素治疗无反应后的慢性期CML患者[CP]，n = 139；加速期[AP]，n = 80；髓系原始细胞危象[BC]，n = 76；淋巴系BC和费城染色体阳性急性淋巴细胞白血病，n = 5）的长期预后、缓解率和耐药情况，这些患者在经过4.5年的观察期后于单一中心进入伊马替尼临床试验。
在慢性期，97%的患者实现了血液学缓解，分别有61%和49%的患者实现了主要细胞遗传学缓解（MCR）和完全细胞遗传学缓解（CCR）。在CML病程中更早开始使用伊马替尼的患者实现MCR的机会更高。在加速期，开始使用伊马替尼后的中位生存期为44个月，分别有31%和26%的患者观察到MCR和CCR。在髓系原始细胞危象中，开始使用伊马替尼后及诊断为原始细胞危象后的中位生存期分别为6个月和9个月。在慢性期、加速期和髓系原始细胞危象中，分别有25%、41%和92%的患者出现血液学耐药，45%的患者与BCR-ABL突变相关，58%的患者与克隆进化相关。
数据强调了对接受伊马替尼治疗的患者进行长期随访的必要性，以确定该药物的临床潜力并建立优化治疗的方法。
