PDF(Pubmed)
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.
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); p = 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.
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); p = 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：ABL1酪氨酸激酶抑制剂停药已成为慢性粒细胞白血病慢性期患者（CML-CP）的治疗目标之一。建立无治疗缓解（TFR）的成功预后因素，有必要诊断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。最近的研究已经确定中性粒细胞在癌症免疫学中起着至关重要的作用。
方法：本研究是一项多中心回顾性观察研究，目的是检查TKI停药前TFR与中性粒细胞计数之间的相关性。调查包括费城染色体阳性CML-CP的患者，他们在2012年1月至2021年7月期间在日本的四家机构进行了持久的深层分子反应后，试图停用TKIs。
结果：118例CML-CP患者中，TKIs停止，估计36个月的TFR率为65.1%。52例患者接受了第二代TKIs作为前线治疗。在接受第二代TKIs作为前线[（HR，0.235（95%，置信区间(CI)0.078-0.711)；p=0.010]。
结论：我们的临床观察支持，中性粒细胞介导的免疫调节可能是CML中有效实现TFR的重要组成部分。
方法：本研究是一项多中心回顾性观察研究，目的是检查TKI停药前TFR与中性粒细胞计数之间的相关性。调查包括费城染色体阳性CML-CP的患者，他们在2012年1月至2021年7月期间在日本的四家机构进行了持久的深层分子反应后，试图停用TKIs。
结果：118例CML-CP患者中，TKIs停止，估计36个月的TFR率为65.1%。52例患者接受了第二代TKIs作为前线治疗。在接受第二代TKIs作为前线[（HR，0.235（95%，置信区间(CI)0.078-0.711)；p=0.010]。
结论：我们的临床观察支持，中性粒细胞介导的免疫调节可能是CML中有效实现TFR的重要组成部分。
