Senapati Jayastu, Jabbour Elias, Kantarjian Hagop, Short Nicholas J
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Leukemia. 2023 Jan;37(1):5-17. doi: 10.1038/s41375-022-01736-5. Epub 2022 Oct 29.
The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) has been a model for cancer therapy development. Though most patients with CML have a normal quality and duration of life with TKI therapy, some patients progress to accelerated phase (AP) and blast phase (BP), both of which have a relatively poor prognosis. The rates of progression have reduced significantly from over >20% in the pre-TKI era to <5% now, largely due to refinements in CML therapy and response monitoring. Significant insights have been gained into the mechanisms of disease transformation including the role of additional cytogenetic abnormalities, somatic mutations, and other genomic alterations present at diagnosis or evolving on therapy. This knowledge is helping to optimize TKI therapy, improve prognostication and inform the development of novel combination regimens in these patients. While patients with de novo CML-AP have outcomes almost similar to CML in chronic phase (CP), those transformed from previously treated CML-CP should receive second- or third- generation TKIs and be strongly considered for allogeneic stem cell transplantation (allo-SCT). Similarly, patients with transformed CML-BP have particularly dismal outcomes with a median survival usually less than one year. Combination regimens with a potent TKI such as ponatinib followed by allo-SCT can achieve long-term survival in some transformed BP patients. Regimens including venetoclax in myeloid BP or inotuzumab ozogamicin or blinatumomab in lymphoid BP might lead to deeper and longer responses, facilitating potentially curative allo-SCT for patients with CML-BP once CP is achieved. Newer agents and novel combination therapies are further expanding the therapeutic arsenal in advanced phase CML.
使用酪氨酸激酶抑制剂（TKIs）治疗慢性髓性白血病（CML）一直是癌症治疗发展的典范。尽管大多数CML患者接受TKI治疗后生活质量和生存期正常，但仍有一些患者进展为加速期（AP）和急变期（BP），这两个阶段的预后都相对较差。进展率已从TKI时代之前的超过20%显著降至目前的<5%，这主要归功于CML治疗和反应监测的改进。在疾病转化机制方面已取得重大进展，包括诊断时或治疗过程中出现的其他细胞遗传学异常、体细胞突变和其他基因组改变的作用。这些知识有助于优化TKI治疗、改善预后，并为这些患者制定新的联合治疗方案提供依据。虽然初发CML-AP患者的预后与慢性期（CP）CML患者几乎相似，但那些由先前治疗的CML-CP转化而来的患者应接受第二代或第三代TKI治疗，并强烈考虑进行异基因干细胞移植（allo-SCT）。同样，CML-BP转化患者的预后特别差，中位生存期通常不到一年。使用强效TKI（如波纳替尼）联合allo-SCT的治疗方案可使一些转化型BP患者获得长期生存。包括维奈克拉用于髓系BP、或伊尼妥单抗奥佐米星或博纳吐单抗用于淋巴系BP的治疗方案可能会带来更深、更长时间的反应，一旦达到CP，可为CML-BP患者促成潜在的治愈性allo-SCT。新型药物和新的联合疗法正在进一步扩大晚期CML的治疗手段。
