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Abstract：
Introduction The overall survival (OS) of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has improved with the combination of tyrosine kinase inhibitor (TKI) with intensive chemotherapy. In recent years, there has been increased interest in the possibility of long-term survival without allogeneic hematopoietic stem cell transplantation (HSCT) or maintenance therapy. The aim of this study was to determine the effectiveness of treatment and the resultant outcomes in Ph+ALL patients using real-world data. Methods We performed a single-center retrospective analysis utilizing Akita University Hospital data (Akita, Japan) from November 2000 to June 2023 to evaluate the outcomes of TKI with intensive chemotherapy for Ph+ALL. Results Twenty-three patients with Ph+ALL were treated with intensive chemotherapy combined with TKI, including six imatinib, four dasatinib, and 13 ponatinib. The median patient age was 53 years (range; 28-67). Eighteen patients (78%) achieved complete molecular remission (CMR) within three months. HSCT was performed in 16 patients (70%), all of whom did not receive post-transplant TKI maintenance therapy. Six of the seven patients who did not undergo HSCT received maintenance therapy with ponatinib after intensive chemotherapy. The three-year OS was 81%. Ponatinib treatment resulted in a much higher OS rate than imatinib/dasatinib (100% vs. 60%; P=0.011). CMR within three months was identified as a prognostic factor for molecular relapse-free survival (hazard ratio (HR)=0.22; P=0.027). CD20 positivity was identified as a risk factor for hematological relapse (HR=5.2, P=0.032). Conclusion Even in a single-center cohort study, ponatinib, as a combination TKI with intensive chemotherapy or maintenance therapy, may improve the prognosis of Ph+ALL. Patients with CMR within three months might not necessarily need to receive HSCT, but a subsequent treatment-free status could have been achieved only by HSCT. Furthermore, CD20 positivity may be a useful biomarker for future treatment decisions in patients with Ph+ALL.
摘要：
介绍酪氨酸激酶抑制剂(TKI)与强化化疗的组合改善了费城染色体阳性急性淋巴细胞白血病(Ph+ALL)的总生存期(OS)。近年来,在没有异基因造血干细胞移植(HSCT)或维持治疗的情况下,人们对长期存活的可能性越来越感兴趣.本研究的目的是使用真实世界数据确定Ph+ALL患者的治疗效果和结果。方法我们利用秋田大学医院的数据进行了单中心回顾性分析(秋田，日本）从2000年11月至2023年6月评估TKI联合强化化疗治疗Ph+ALL的结果。结果23例Ph+ALL患者采用强化化疗联合TKI治疗,包括六个伊马替尼，四个达沙替尼，和13普纳替尼。患者年龄中位数为53岁（范围；28-67）。18名患者（78％）在三个月内实现了完全分子缓解（CMR）。16例患者（70%）进行了HSCT，所有患者均未接受移植后TKI维持治疗.7例未接受HSCT的患者中有6例在强化化疗后接受了ponatinib维持治疗。三年OS为81%。Ponatinib治疗的OS率远高于伊马替尼/达沙替尼（100％vs.60%;P=0.011)。三个月内的CMR被确定为分子无复发生存的预后因素(风险比(HR)=0.22;P=0.027)。CD20阳性被确定为血液学复发的危险因素(HR=5.2,P=0.032)。结论即使在单中心队列研究中，普纳替尼,作为TKI与强化化疗或维持治疗的组合，可能改善Ph+ALL的预后。三个月内患有CMR的患者可能不一定需要接受HSCT，但只有通过HSCT才能实现随后的无治疗状态.此外，CD20阳性可能是Ph+ALL患者未来治疗决策的有用生物标志物。
