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酪氨酸激酶抑制剂治疗慢性髓性白血病患者合并症的预后影响。

Prognostic effect of comorbidities in patients with chronic myeloid leukemia treated with a tyrosine kinase inhibitor.

机构信息

Divison of Hematology, Hamamatsu University School of Medicine, Shizuoka, Japan.

Department of Hematology, Nephrology, and Rheumatology, Akita University School of Medicine, Akita, Japan.

出版信息

Cancer Sci. 2020 Oct;111(10):3714-3725. doi: 10.1111/cas.14580. Epub 2020 Aug 12.

Abstract

Comorbidities at diagnosis among patients with chronic myeloid leukemia in chronic phase (CML-CP) may affect their overall survival (OS) rate even in the tyrosine kinase inhibitor (TKI) era. However, the prognostic impact of comorbidities in patients with CML-CP treated with a second-generation TKI (2GTKI) has not been elucidated. We evaluated the effect of comorbidities on survival using the Charlson Comorbidity Index (CCI) in patients with CML-CP treated with imatinib or a 2GTKI (nilotinib and dasatinib). From April 2010 to March 2013, 506 patients with CML-CP were registered for the population-based cohort study, and 452 with a median age of 56 y were assessable. Treatment groups included 139 patients receiving imatinib, 169 receiving nilotinib, and 144 receiving dasatinib. Comorbidities were diagnosed in 99 patients. CCI scores were stratified as follows: 2, 353 patients; 3, 72 patients; and ≥4, 27 patients. Treatment response did not vary relative to CCI scores. However, across the entire cohort, the OS rate was significantly lower among patients with higher CCI scores than in those with a CCI score of 2 (94.4% in score 2, 89.0% in score 3, and 72.8% in score ≥4; P < .001). Multivariate analysis identified a CCI score of ≥4 as a strong adverse prognostic factor for OS rather than the disease-specific risk factor, older age, performance status, or selection of TKI (Wald test, P < .01). Our results demonstrated that comorbidities at diagnosis were the most important predictive factor for successful treatment, regardless of the TKI type used in CML-CP. This trial was registered at UMIN-CTR as 00003581.

摘要

在酪氨酸激酶抑制剂(TKI)时代,慢性期慢性髓系白血病(CML-CP)患者的合并症可能会影响其总生存(OS)率。然而,在接受第二代 TKI(2GTKI)治疗的 CML-CP 患者中,合并症的预后影响尚未阐明。我们使用 Charlson 合并症指数(CCI)评估了 CML-CP 患者接受伊马替尼或 2GTKI(尼洛替尼和达沙替尼)治疗时的生存情况。从 2010 年 4 月至 2013 年 3 月,对 506 名 CML-CP 患者进行了基于人群的队列研究登记,其中 452 名患者的中位年龄为 56 岁,可评估。治疗组包括 139 名接受伊马替尼治疗的患者、169 名接受尼洛替尼治疗的患者和 144 名接受达沙替尼治疗的患者。99 名患者被诊断患有合并症。CCI 评分分为以下几类:2,353 例;3,72 例;和≥4,27 例。治疗反应与 CCI 评分无关。然而,在整个队列中,CCI 评分较高的患者的 OS 率明显低于 CCI 评分为 2 的患者(CCI 评分为 2 的患者为 94.4%,CCI 评分为 3 的患者为 89.0%,CCI 评分为≥4 的患者为 72.8%;P<.001)。多变量分析确定 CCI 评分≥4 是 OS 的一个强烈不利预后因素,而不是疾病特异性危险因素、年龄较大、表现状态或 TKI 的选择(Wald 检验,P<.01)。我们的结果表明,诊断时的合并症是成功治疗的最重要预测因素,而与 CML-CP 中使用的 TKI 类型无关。该试验在 UMIN-CTR 注册为 00003581。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8e9/7541002/2d7178931e4f/CAS-111-3714-g001.jpg

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