Molecular response and prognosis of pediatric patients with Ph-positive acute lymphoblastic leukemia treated by tyrosine kinase inhibitors with chemotherapy

Q4 Medicine

中华实用儿科临床杂志 Pub Date : 2020-03-19 DOI:10.3760/CMA.J.CN101070-20190222-00125

Yu-Juan Xue, A. Lu, Jun Wu, Y. Zuo, Y. Jia, Le-ping Zhang

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引用次数: 1

Abstract

Objective To explore the molecular response and prognostic factors of pediatric patients with Ph-positive acute lymphoblastic leukemia (Ph+ ALL) treated by tyrosine kinase inhibitors (TKI) with chemotherapy in TKI era. Methods The clinical data of children newly diagnosed with Ph+ ALL admitted at Department of Pediatrics, Peking University People′s Hospital from August 2006 to February 2017 were retrospectively reviewed.The molecular biological characteristics and survival prognosis of the 30 patients who received continuous TKI with chemotherapy from early induction combined and no subsequent transplantation were analyzed. Results The 30 patients with Ph+ ALL had 19 males and 11 females with a median age of 8-year-old (ranging from 2 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 96.7% (29/30 cases), with overall CR rate of 100.0%; Before treatment, the mean level of BCR/ABL mRNA in the 30 patients was 73.2% (0.12%-160.60%) and the level declined significantly with the progression of chemotherapy courses, reaching the plateau stage at the 6th month of chemotherapy (Z=-1.922, P>0.05); nine patients had recurrence, with a median recurrence time of 7 months (3.7-58.8 months). Univariate analysis showed that age (P<0.05), the lever of minimal residual disease (MRD) after induction chemotherapy (P<0.01) and the MRD level at the 3th month of induction chemotherapy (P<0.01) affected the recurrence rate.The median follow-up time of 30 patients was 42.6 months (6.4-96.5 months), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were (78.6±7.8)% and (72.4±8.4)%, respectively; Cox multivariate analysis showed that the initial white blood cell count ≥34.0×109/L (OR=11.955, 95% CI: 1.075-132.899, P<0.05) and BCR/ABL mRNA reduction less than 3 log from baseline [major molecular response (MMR)] at the 3th month of induction chemotherapy (OR=8.563, 95% CI: 1.254-58.478, P<0.05) were independent risk factors affecting the 3-year EFS rate.In addition, the initial white blood cell count ≥34.0×109/L (OR=14.327, 95% CI: 1.843-243.592, P<0.05) was also an independent risk factor affecting the 3-year OS rate. Conclusions The application of TKI can significantly deepen the molecular response of Ph+ ALL in children.In the TKI era, the initial white blood cell count ≥ 34.0×109/L and BCR/ABL mRNA reduction less than 3 log from baseline (MMR) at the 3th month of induction chemotherapy are independent risk factors for the long-term survival of pediatric Ph+ ALL. Key words: Philadelphia chromosome; Acute lymphoblastic leukemia; Child; Tyrosine kinase inhibitor; Mole-cular response

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酪氨酸激酶抑制剂联合化疗治疗Ph阳性急性淋巴细胞白血病患儿的分子反应及预后

目的探讨酪氨酸激酶抑制剂（TKI）联合化疗治疗Ph阳性急性淋巴细胞白血病（Ph+ALL）患儿的分子反应及预后因素。方法回顾性分析2006年8月至2017年2月北京大学人民医院儿科收治的Ph+ALL患儿的临床资料。分析了30例从早期诱导联合化疗到无后续移植的连续TKI患者的分子生物学特征和生存预后。结果30例Ph+ALL患者，男19例，女11例，中位年龄8岁（2~16岁）。诱导化疗第一周期后完全缓解率为96.7%（29/30例），总CR率为100.0%；30例患者治疗前BCR/ABL mRNA平均水平为73.2%（0.12%-160.60%），随着化疗进程的进行，BCR/ABLmRNA水平明显下降，化疗6个月达到平稳期（Z=-1.922，P>0.05）；9例复发，中位复发时间为7个月（3.7-58.8个月）。单因素分析显示，年龄（P＜0.05）、诱导化疗后最小残留病变（MRD）水平（P＜0.01）和诱导化疗第3个月MRD水平（P＞0.01）影响复发率。30例患者的中位随访时间为42.6个月（6.4-96.5个月），3年总生存率（OS）和无事件生存率（EFS）分别为（78.6±7.8）%和（72.4±8.4）%；Cox多变量分析显示，诱导化疗第3个月时，初始白细胞计数≥34.0×109/L（OR=11.955，95%CI:1.075-132.899，P<0.05）和BCR/ABL mRNA自基线[主要分子反应（MMR）]减少小于3 log（OR=8.563，95%CI:1.254-58.478，P<0.05）是影响3年EFS发生率的独立危险因素。此外，初始白细胞计数≥34.0×109/L（OR=14.327，95%CI:1.843-243.592，P<0.05）也是影响3年OS发生率的独立危险因素。结论TKI的应用可显著加深儿童Ph+ALL的分子应答。在TKI时代，诱导化疗第3个月时，初始白细胞计数≥34.0×109/L和BCR/ABL mRNA自基线减少小于3 log（MMR）是儿童Ph+ALL长期生存的独立风险因素。关键词：费城染色体；急性淋巴细胞白血病；儿童；酪氨酸激酶抑制剂；鼹鼠反应

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来源期刊

中华实用儿科临床杂志 Medicine-Pediatrics, Perinatology and Child Health

CiteScore

0.60

自引率

0.00%

发文量

14243

期刊介绍： Chinese Journal of Applied Clinical Pediatrics ( semi-monthly ) is a core journal of paediatrics under the supervision of China Association for Science and Technology, sponsored by Chinese Medical Association and undertaken by Xinxiang Medical College. Founded in 1986, it is openly circulated both at home and abroad. The journal has several columns, such as Expert Forum, Experimental Research and Paediatric Surgery, which are mainly for paediatric medical workers and medical researchers in hospitals. Its purpose is to reflect the new theories and technologies in paediatric medicine and scientific research at home and abroad, and to promote academic exchanges. Chinese Journal of Applied Clinical Pediatrics is a source journal of China Science Citation Database (CSCD), a core journal of Peking University, a source journal of Chinese science and technology paper statistics (China Science and Technology Core Journals), a core academic journal of RCCSE, a high-quality scientific and technical journal of China, a high-quality scientific and technical journal of China Association for Science and Technology, and a high-quality scientific and technical journal of China Biomedical Science and Technology Association. We have been published in China Biomedical Literature Database (SinoMed), China Knowledge Network, Wanfang Data Knowledge Service Platform, China Academic Journal Abstracts, Scopus Database, Chemical Abstracts (USA), Japan Science and Technology Agency (JSTA) Database, Copernicus Abstracts (Poland), Abstracts of the Centre for Agricultural and Biological Sciences (CABS) of the United Kingdom, Cambridge Scientific Abstracts ProQuest Database, WHO Medical Journal of the Western Pacific Region (WMPR), and WHO Medical Journal of the Western Pacific Region (WMPR) of the United States. We have been included in dozens of authoritative databases at home and abroad, such as WHO Western Pacific Region Index of Medicine (WPRIM), Ullrich's Guide to Periodicals, and so on.