DeAngelo Daniel J, Stein Eytan M, Ravandi Farhad
From the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY; The University of Texas MD Anderson Cancer Center, Houston, TX.
Am Soc Clin Oncol Educ Book. 2016;35:e302-12. doi: 10.1200/EDBK_161258.
Acute myeloid leukemia (AML) is an acquired disease characterized by chromosomal translocations and somatic mutations that lead to leukemogenesis. Systemic combination chemotherapy with an anthracycline and cytarabine remains the standard induction regimen for "fit" adults. Patients who achieve complete remission generally receive postinduction therapy with cytarabine-based chemotherapy or an allogeneic bone marrow transplant. Those unfit for induction chemotherapy are treated with hypomethylating agents (HMAs), low-dose cytarabine, or they are offered supportive care alone with transfusions and prophylactic antimicrobials. The revolution in understanding the genetics of AML, facilitated by next-generation sequencing, has led to many new drugs against driver mutations. Better methods of identification of leukemic blasts have provided us with better means to detect the disease left behind after cytotoxic chemotherapy regimens. This measurable residual disease has been correlated with poorer relapse-free survival, demonstrating the need for novel strategies to eradicate it to improve the outcome of patients with acute leukemias. In this article, we discuss adapting and improving AML therapy by age and comorbidities, emerging targeted therapies in AML, and minimal residual disease (MRD) assessment in AML.
急性髓系白血病(AML)是一种后天性疾病,其特征为染色体易位和体细胞突变,可导致白血病发生。蒽环类药物和阿糖胞苷的全身联合化疗仍然是“适合”成人患者的标准诱导方案。达到完全缓解的患者通常接受以阿糖胞苷为基础的化疗或异基因骨髓移植的诱导后治疗。那些不适合进行诱导化疗的患者则接受去甲基化药物(HMAs)、小剂量阿糖胞苷治疗,或者仅接受输血和预防性抗菌药物的支持性治疗。在新一代测序技术的推动下,对AML遗传学的认识取得了革命性进展,催生了许多针对驱动突变的新药。更好的白血病原始细胞鉴定方法为我们提供了更好的手段来检测细胞毒性化疗方案后残留的疾病。这种可测量的残留病与较差的无复发生存率相关,这表明需要新的策略来根除它,以改善急性白血病患者的治疗结果。在本文中,我们将讨论如何根据年龄和合并症调整和改进AML治疗、AML中新兴的靶向治疗以及AML中的微小残留病(MRD)评估。