Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):122-128. doi: 10.1182/hematology.2021000240.
Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). With TKI therapy, the percentage of patients who progress to accelerated phase (AP) or blast phase (BP) CML has decreased from more than 20% to 1% to 1.5% per year. Although AP- and BP-CML occur in a minority of patients, outcomes in these patients are significantly worse compared with chronic phase CML, with decreased response rates and duration of response to TKI. Despite this, TKIs have improved outcomes in advanced phase CML, particularly in de novo AP patients, but are often inadequate for lasting remissions. The goal of initial therapy in advanced CML is a return to a chronic phase followed by consideration for bone marrow transplantation. The addition of induction chemotherapy with TKI is often necessary for achievement of a second chronic phase. Given the small population of patients with advanced CML, development of novel treatment strategies and investigational agents is challenging, although clinical trial participation is encouraged in AP and BP patients, whenever possible. We review the overall management approach to advanced CML, including TKI selection, combination therapy, consideration of transplant, and novel agents.
酪氨酸激酶抑制剂（TKIs）彻底改变了慢性髓性白血病（CML）的治疗方法。有了 TKI 治疗，进展为加速期（AP）或急变期（BP）CML 的患者比例从每年超过 20%降至 1%至 1.5%。尽管 AP 和 BP-CML 发生在少数患者中，但与慢性期 CML 相比，这些患者的预后明显更差，对 TKI 的反应率和反应持续时间均降低。尽管如此，TKIs 还是改善了晚期 CML 的预后，尤其是在初发 AP 患者中，但通常不足以实现持久缓解。晚期 CML 初始治疗的目标是恢复为慢性期，然后考虑进行骨髓移植。通常需要加入 TKI 的诱导化疗来实现第二个慢性期。由于晚期 CML 患者人数较少，开发新的治疗策略和研究药物具有挑战性，尽管尽可能鼓励 AP 和 BP 患者参与临床试验。我们综述了晚期 CML 的整体管理方法，包括 TKI 选择、联合治疗、移植考虑因素和新型药物。
