TKIs联合化疗治疗成人Ph阳性急性淋巴细胞白血病的疗效及预后分析

Efficacy and prognosis of tyrosine kinase inhibitors combined with chemotherapy in the treatment of adult Philadelphia chromosome–positive acute lymphoblastic leukemia

    摘要
  • 摘要:
    目的 探讨成人费城染色体阳性急性淋巴细胞白血病（Philadelphia chromosome-positive acute lymphoblastic leukemia，Ph+ALL）患者化疗及酪氨酸激酶抑制剂（tyrosine kinase inhibitors，TKI）联合化疗作为首次诱导治疗的疗效及预后。
    方法 回顾性分析2012年1月至2023年10月就诊于宁夏医科大学总医院的60例成人Ph+ALL 患者临床特点、生物学特征及完全缓解情况，分析其疗效及预后。
    结果 首次诱导治疗后达到完全缓解率（complete response，CR）的患者有43例，占71.67%（43/60），其中单纯化疗组7例，占41.18%（7/17），TKI+化疗组 CR 率为36例，占83.72%（36/43），且两组差异具有统计学意义（P=0.003）。单纯化疗组患者的2年总生存（overall survival，OS）率为28.2%，TKI联合化疗组患者的2年OS率为56%，差异具有统计学意义（P=0.041）。移植组与非移植组患者2年OS率76.9% vs. 51.9%，5年OS率56.1% vs. 19.4%，（P=0.003）；2年无进展生存（progression-free survival，PFS）率38.5% vs. 12.1%（P=0.018），二者差异均具有统计学意义。单因素预后分析示，是否选择TKI、初次诱导治疗后是否获得CR和是否骨髓移植对OS预后差异均具有统计学意义（P<0.05）；白细胞计数、是否选择TKI对患者无复发生存（relapse-free survival，RFS）率差异具有统计学意义（P<0.05）。Cox多因素预后分析示，诱导治疗后获得CR、后续接受造血干细胞移植为患者OS的独立预后因素。
    结论 Ph+ALL 诱导治疗方案中，TKI+化疗诱导治疗方案能够实现早缓解，高缓解率，总生存期方面优于单纯化疗。缓解后进行骨髓造血干细胞移植治疗Ph+ALL预后良好。

     

    Abstract:
    Objective To investigate the efficacy and prognosis of induction therapy combined with chemotherapy and tyrosine kinase inhibitors (TKI) in adult Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL).
    Methods This study retrospectively analyzed the clinical features, biological characteristics, complete remission,curative effect, and prognosis of 60 adult patients with Ph+ALL treated in GeneraI Hospital of Ningxia Medical University from January 2012 to October 2023.
    Results Among the patients, 43 (71.67%, 43/60) achieved complete remission (CR) after the first induction therapy, including 7 (41.18%, 7/17) in the chemotherapy-alone group and 36 (83.72%, 36/43) in the TKI-plus-chemotherapy group (P=0.003). The 2-year overall survival (OS) rate of patients in the chemotherapy-alone group (28.2%) was significantly less than that of patients in the TKI-plus-chemotherapy group (56%, P=0.041). In the transplant and non-transplant groups, the 2-year and 5-year OS rates were 76.9% vs. 51.9%, 56.1% vs. 19.4%, respectively (P=0.003). The 2-year progression-free survival (PFS) rate was better in the transplant group (38.5%) than in the non-transplant group (12.1%, P=0.018). Univariate prognostic analysis showed that whether TKI was selected, whether CR was obtained after the initial induction therapy, and whether bone marrow transplantation was performed, significantly affected OS prognosis (P<0.05). The white blood cell count and whether TKI was selected significantly affected the relapse-free survival (RFS) of patients (P<0.05). Cox multivariate prognostic analysis showed that CR, after induction therapy, and subsequent hematopoietic stem cell transplantation were independent prognostic factors for OS.
    Conclusions In the Ph+ALL induction therapy regimens, TKI-plus-chemotherapy induction therapy can achieve early remission and a high remission rate, and the OS is better than chemotherapy alone. After CR, bone marrow hematopoietic stem cell transplantation for Ph+ALL had a good prognosis.

     

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