2013年慢性粒细胞白血病和其他慢性骨髓增殖性肿瘤的研究进展

Update on chronic myelogenous leukemia and other chronic myeloproliferative neoplasms in 2013

酪氨酸激酶抑制剂(TKIs)已成为治疗慢性粒细胞白血病的首选治疗药物,目前3种TKIs可用于一线选择,如何选择一线TKIs、当治疗失败或不耐受时又如何转换治疗、如何进行分子学监测和及时判断治疗失败的高危患者仍是困扰临床医生的一些问题。其他慢性骨髓增殖性肿瘤中除Janus激酶(JAK)突变以外很多新的基因突变被发现,(JAK)抑制剂ruxolitinib已应用于骨髓纤维化的治疗,其他多种JAK抑制剂也已进入临床试验。其剂量及安全性以及如何最大限度减少骨髓抑制是临床医生面临的问题。现就上述内容做一综述。

With the approval in many countries of three available tyrosine kinase inhibitors（TKIs） for frontline therapy in chronic myelogenous leukemia（CML）,clinicians now have to make difficult choice.Whatever first choice of TKIs is made,treatment failure or intolerance must be recognized early because a prompt switch to another TKIs likely provides the best chance of achieving optimal response.However,careful monitoring and assessment of adherence are essential for successful outcomes and for identifying patients at risk for failing therapy.Recently,much more mutations except JAK have been described in patients with chronic myeloproliferitive neoplasms.The JAK1/JAK2 inhibitor ruxolitinib is approved for treatment of myelofibrosis in North America and Europe and other JAK inhibitors have entered the advanced phases of trial investigation.A major challenge for practitioners is how to optimize dosing of these agents to secure clinically relevant and durable benefits while minimizing bone marrow suppression.Here,we review the above issues.