Short Nicholas J, Kantarjian Hagop, Jabbour Elias, Ravandi Farhad
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Best Pract Res Clin Haematol. 2017 Sep;30(3):193-200. doi: 10.1016/j.beha.2017.05.001. Epub 2017 Jun 15.
The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens has significantly improved the long-term survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Successive generations of TKIs with increased potency against BCR-ABL and broader spectrum of activity against ABL kinase domain mutations have led to incremental improvements in the outcomes of patients with this disease. In particular, ponatinib, a potent pan-BCR-ABL TKI capable of overcoming the T315I mutation, holds significant promise in the treatment of Ph+ ALL, although the potential cardiovascular toxicity of this agent remains a concern. With the development of more potent TKIs that are capable of inducing deep and sustained remissions, future studies re-evaluating the need for intensive chemotherapy as well as the role for stem cell transplantation in first remission for patients with Ph+ ALL are warranted.
将酪氨酸激酶抑制剂（TKIs）纳入化疗方案显著提高了费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者的长期生存率。一代又一代对BCR-ABL活性增强且对ABL激酶结构域突变活性谱更广的TKIs，使该疾病患者的治疗结果逐步改善。特别是波纳替尼，一种能够克服T315I突变的强效泛BCR-ABL TKI，在Ph+ ALL治疗中具有重大前景，尽管该药物潜在的心血管毒性仍令人担忧。随着能够诱导深度和持续缓解的更有效TKIs的研发，有必要开展未来研究，重新评估Ph+ ALL患者强化化疗的必要性以及首次缓解时干细胞移植的作用。
