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 (ALL), the most frequent genetic subgroup in adult ALL, whose incidence increases with age and whose prognosis, before the advent of tyrosine kinase inhibitors (TKIs), was particularly poor. The outcome and management of patients with Ph+ ALL have greatly improved since the incorporation of first-, second-, and third-generation TKIs in the therapeutic backbone and is further changing with the more recent introduction of immunotherapy. This allows for 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 article, illustrative clinical cases are used to discuss the current role 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 are discussed.

中文翻译：

---

我如何治疗成人 Ph+ ALL


费城 （Ph） 染色体是为数不多的已证实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 （ALL） 的情况下也很明显，这是成人 ALL 中最常见的遗传亚组，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 纳入治疗支柱以来，Ph+ ALL 患者的预后和管理已大大改善，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。因此，成人 Ph+ ALL 的临床情况发生了深刻的变化，新的挑战正在出现。在本文中，使用说明性临床病例来讨论全身化疗和同种异体干细胞移植的当前作用、治疗中枢神经系统复发的困难，更一般地说，在当前治疗时代治疗复发，以及停止 TKI 的可能性。最后，讨论了与这些患者的最佳管理相关的挑战。