Ureshino Hiroshi, Takeda Yusuke, Kamachi Kazuharu, Ono Takaaki, Iriyama Noriyoshi, Ohtsuka Eiichi, Sakaida Emiko, Kimura Shinya
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.
Clin Pract. 2024 Jun 21;14(4):1216-1224. doi: 10.3390/clinpract14040097.
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.
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.
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].
The neutrophil-mediated immunomodulation can be a significant component for the effective achievement of TFR in CML supported by our clinical observation.
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。
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。
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]。
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。
