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诱导治疗期间绝对中性粒细胞计数低是儿童急性淋巴细胞白血病的不良预后因素。

Low absolute neutrophil count during induction therapy is an adverse prognostic factor in childhood acute lymphoblastic leukaemia.

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

出版信息

Ann Hematol. 2021 Sep;100(9):2269-2277. doi: 10.1007/s00277-021-04412-3. Epub 2021 Jan 14.

Abstract

Variation in normal blood cells during chemotherapy has not been recognised as a risk factor guiding chemotherapy in childhood acute lymphoblastic leukaemia (ALL). This study aims to explore whether variations in normal haematopoiesis determine prognosis as well as to improve risk-stratified treatment in childhood ALL. A retrospective study of 279 cases of ALL treated with the CCCG-ALL-2015 regimen in the Division of Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from May 2015 to January 2017 was performed to analyse the prognostic impact of blood cell levels on day 19 of induction therapy by Kaplan-Meier method. Patients with childhood ALL with absolute neutrophil count (ANC) ≤ 90 cells/μl, absolute monocyte count (AMC) ≤ 10 cells/μl or absolute lymphocyte count (ALC) ≤ 1000 cells/μl on day 19 of induction therapy had a lower event-free survival (EFS) rate than those with higher values (all P < 0.05). Multivariate analysis confirmed that ANC ≤ 90 cells/μl and ALC ≤ 1000 cells/μl were independent adverse prognostic factors (HR = 1.981 and 2.162, respectively, both P < 0.05). Among patients with minimal residual disease (MRD) < 1% on day 19 of induction therapy, those with ANC ≤ 90 cells/μl had lower EFS than those with ANC > 90 cells/μl (70.8 ± 6.1% vs 86.4 ± 3.1%, P = 0.001). In the subgroup with the BCR/ABL1 fusion gene, patients with ANC ≤ 90 cells/μl on day 19 of induction therapy also had lower EFS than those with ANC > 90 cells/μl (34.4 ± 25.2% vs 25.0 ± 21.7%, P = 0.041). ANC and ALC during induction therapy are independent prognostic factors for childhood ALL. ANC contributes to guiding the prognosis of patients with low-level MRD or the BCR/ABL1 fusion gene.

摘要

化疗期间正常血细胞的变化尚未被视为指导儿童急性淋巴细胞白血病(ALL)化疗的危险因素。本研究旨在探讨正常造血的变化是否能决定预后,并改善儿童 ALL 的风险分层治疗。对 2015 年 5 月至 2017 年 1 月在中国医学科学院血液病医院儿童血液疾病中心接受 CCCG-ALL-2015 方案治疗的 279 例 ALL 患者进行回顾性研究,采用 Kaplan-Meier 法分析诱导治疗第 19 天血细胞水平对预后的影响。诱导治疗第 19 天绝对中性粒细胞计数(ANC)≤90 个/μl、绝对单核细胞计数(AMC)≤10 个/μl 或绝对淋巴细胞计数(ALC)≤1000 个/μl 的儿童 ALL 患者无事件生存率(EFS)低于ANC 值较高的患者(均 P<0.05)。多因素分析证实 ANC≤90 个/μl 和 ALC≤1000 个/μl 是独立的不良预后因素(HR 分别为 1.981 和 2.162,均 P<0.05)。在诱导治疗第 19 天微小残留病(MRD)<1%的患者中,ANC≤90 个/μl 的患者 EFS 低于 ANC>90 个/μl 的患者(70.8±6.1%比 86.4±3.1%,P=0.001)。在 BCR/ABL1 融合基因亚组中,诱导治疗第 19 天 ANC≤90 个/μl 的患者 EFS 也低于 ANC>90 个/μl 的患者(34.4±25.2%比 25.0±21.7%,P=0.041)。诱导治疗期间的 ANC 和 ALC 是儿童 ALL 的独立预后因素。ANC 有助于指导低水平 MRD 或 BCR/ABL1 融合基因患者的预后。

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