费城 (Ph) 染色体是少数已被证明会造成伤亡的遗传畸变之一，因此代表了医学史上的成功。这在 Ph 急性淋巴细胞白血病 (Ph ALL) 的情况中也很明显，Ph ALL 是成人 ALL 中最常见的遗传亚型，其发病率随着年龄的增长而增加，并且在酪氨酸激酶抑制剂 (TKI) 出现之前，其预后特别差。自从第一代、第二代和第三代 TKI 纳入治疗主干以来，Ph ALL 患者的预后和治疗得到了极大改善，并且随着最近免疫疗法的引入而进一步改变。这使得目前的长期生存率在 75% 到 80% 之间。成人Ph ALL的临床情况因此发生了深刻的变化，新的挑战正在出现。在这篇《我如何治疗》中，使用说明性临床案例来讨论当今全身化疗和同种异体干细胞移植的作用、治疗中枢神经系统复发的困难，以及更一般地说，当前治疗时代的复发，以及停止 TKI。最后，讨论了与这些患者的最佳管理相关的挑战。版权所有 © 2024 美国血液学会。

The Philadelphia (Ph) chromosome is one of the few genetic aberrations in which a casualty has been proven, and as such represents a success in the history of medicine. This is also evident in the setting of Ph+ acute lymphoblastic leukemia (Ph+ ALL), the most frequent genetic subgroup in adult ALL, whose incidence increases with age and whose prognosis, prior to the advent of tyrosine kinase inhibitors (TKIs), was particularly poor. The outcome and management of Ph+ ALL patients have greatly improved since the incorporation of 1st, 2nd and 3rd generations TKIs in the therapeutic backbone, and is further changing with the more recent introduction of immunotherapy. This is allowing long-term survival rates currently ranging between 75 and 80%. The clinical scenario of adult Ph+ ALL has thus changed profoundly, and new challenges are emerging. In this How I treat, illustrative clinical cases are used to discuss the role today of systemic chemotherapy and allogeneic stem cell transplant, the difficulty in treating central nervous system relapses and, more in general, relapses in the current therapeutic era, and the possibility of stopping TKIs. Finally, the challenges related to an optimal management of these patients is discussed.Copyright © 2024 American Society of Hematology.