These limitations are primarily caused by low complete molecular responses (CMRs) and T315I kinase domain mutations, thus leaving substantial room for improvement in the treatment of Ph+ ALL.
The clinical adoption of TKIs has resulted in a new clinical paradigm for patients with Ph+ ALL, although first and second-generation TKIs have considerable limitations, including high relapse rates and disappointing long-term survival with a three to five-year OS rate of just about 50%. However, the five-year overall survival (OS) was only less than 30% and more than 70% patients relapsed before the transplantation or simply lacked access to the surgical treatment. Prior to the introduction of TKIs, a class of targeted small molecule compounds, allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving complete responses (CRs) from chemotherapy was widely adopted as a first-line treatment for patients with Ph+ ALL. Accounting for 20%-30% of all ALL cases in adults, Ph+ ALL is commonly associated with a high relapse rate, short progression-free survival (PFS), and poor prognosis.
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