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对于接受第二代酪氨酸激酶抑制剂作为一线治疗的慢性髓性白血病患者,较高的中性粒细胞计数与无治疗缓解的良好实现相关。

A Higher Neutrophil Count Is Associated with Favorable Achievement of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Who Received Second Generation Tyrosine Kinase Inhibitor as Frontline Treatment.

作者信息

Ureshino Hiroshi, Takeda Yusuke, Kamachi Kazuharu, Ono Takaaki, Iriyama Noriyoshi, Ohtsuka Eiichi, Sakaida Emiko, Kimura Shinya

机构信息

Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.

Next Generation Development of Genome and Cellular Therapy Program, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Hiroshima 734-8553, Japan.

出版信息

Clin Pract. 2024 Jun 21;14(4):1216-1224. doi: 10.3390/clinpract14040097.

Abstract

BACKGROUND

ABL1 tyrosine kinase inhibitor discontinuation securely became among the therapeutic goal for chronic myeloid leukemia chronic phase patients (CML-CP). To establish successful prognostic factors for treatment-free remission (TFR), it is necessary to diagnose the patients with high-risk molecular relapse, however, a biomarker for the achievement of TFR has not been completely elucidated. Recent investigations have determined that neutrophils function crucially in cancer immunology.

PATIENTS AND METHODS

The research was a multicenter retrospective observational study to examine the correlation between TFR and neutrophil counts before TKI discontinuation. The investigation included patients having Philadelphia chromosome-positive CML-CP who attempted the discontinuation of TKIs after a durable deep molecular response between January 2012 and July 2021 at four institutions in Japan.

RESULTS

118 CML-CP patients in total discontinued TKIs and an estimated 36-month TFR rate was 65.1%. 52 patients received second-generation TKIs as frontline. Higher neutrophil count (>3210/μL) at TKIs discontinuation was determined as an independent prognostic variable for TFR in patients who received second-generation TKIs as frontline [(HR, 0.235 (95%, confidence interval (CI) 0.078-0.711); = 0.010].

CONCLUSIONS

The neutrophil-mediated immunomodulation can be a significant component for the effective achievement of TFR in CML supported by our clinical observation.

摘要

背景

对于慢性髓性白血病慢性期患者(CML-CP)而言,安全停用ABL1酪氨酸激酶抑制剂已成为治疗目标之一。为确立无治疗缓解(TFR)的成功预后因素,有必要诊断出具有高风险分子复发的患者,然而,尚未完全阐明实现TFR的生物标志物。最近的研究已确定中性粒细胞在癌症免疫学中发挥关键作用。

患者与方法

本研究为多中心回顾性观察研究,旨在探讨TFR与停用酪氨酸激酶抑制剂(TKI)前中性粒细胞计数之间的相关性。该研究纳入了2012年1月至2021年7月期间在日本四家机构尝试在持久深度分子反应后停用TKI的费城染色体阳性CML-CP患者。

结果

共有118例CML-CP患者停用了TKI,估计36个月的TFR率为65.1%。52例患者接受第二代TKI作为一线治疗。对于一线接受第二代TKI治疗的患者,停用TKI时较高的中性粒细胞计数(>3210/μL)被确定为TFR的独立预后变量[风险比(HR),0.235(95%置信区间(CI)0.078 - 0.711);P = 0.010]。

结论

我们的临床观察表明,中性粒细胞介导的免疫调节可能是CML有效实现TFR的重要组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9210/11270167/f1834a777350/clinpract-14-00097-g001.jpg

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