Shah Neil P
Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California, 94143, USA.
J Natl Compr Canc Netw. 2008 Mar;6 Suppl 2:S31-S36.
Tyrosine kinase inhibitor (TKI) therapy has impacted the natural course of chronic myelogenous leukemia (CML), because patients diagnosed as having chronic-phase disease can experience long-lasting responses. However, for patients with advanced CML (accelerated and blast phases), the efficacy of all current therapies is reduced. For these patients, allogeneic stem cell transplantation remains the preferred treatment if a donor is available, although TKIs play a valuable role as a bridging therapy. For patients with accelerated-phase CML, imatinib, dasatinib, and nilotinib have been shown to produce meaningful rates of hematologic and cytogenetic response. Imatinib and dasatinib are also approved for blast-phase CML. Studies with the newer agents have involved heavily pretreated patients; however, response rates have been at least comparable to those achieved with imatinib in previous studies. Therefore, these newer, more potent TKIs will probably be more likely to induce a deep response in previously untreated patients. Moreover, because fewer mechanisms appear to exist for secondary resistance to dasatinib and nilotinib, reducing the potential for disease to escape TKI therapy, these agents may result in improved longer-term outcomes. However, BCR-ABL-independent pathways may also become more important, indicating that other therapeutic targets may also have a future role in managing patients with advanced CML.
酪氨酸激酶抑制剂（TKI）疗法已经影响了慢性粒细胞白血病（CML）的自然病程，因为被诊断为慢性期疾病的患者能够获得持久的缓解。然而，对于晚期CML（加速期和急变期）患者，目前所有疗法的疗效都会降低。对于这些患者，如果有合适的供体，异基因干细胞移植仍是首选的治疗方法，尽管TKI作为一种桥接疗法也发挥着重要作用。对于加速期CML患者，伊马替尼、达沙替尼和尼洛替尼已被证明可产生有意义的血液学和细胞遗传学缓解率。伊马替尼和达沙替尼也被批准用于治疗急变期CML。针对这些新型药物的研究纳入了大量经过充分预处理的患者；然而，其缓解率至少与之前研究中使用伊马替尼所取得的缓解率相当。因此，这些更新的、更有效的TKI可能更有可能在既往未接受治疗的患者中诱导深度缓解。此外，由于对达沙替尼和尼洛替尼产生继发性耐药的机制似乎较少，降低了疾病逃避TKI治疗的可能性，这些药物可能会带来更好的长期疗效。然而，不依赖BCR-ABL的途径可能也会变得更加重要，这表明其他治疗靶点在晚期CML患者的管理中可能也将发挥作用。
