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大剂量阿糖胞苷在接受巩固治疗的急性髓系白血病患者中是否会导致更多真菌感染:一项在中国进行的多中心、前瞻性、观察性研究。

Does High-Dose Cytarabine Cause More Fungal Infection in Patients With Acute Myeloid Leukemia Undergoing Consolidation Therapy: A Multicenter, Prospective, Observational Study in China.

作者信息

Wang Ling, Hu Jiong, Sun Yuqian, Huang He, Chen Jing, Li Jianyong, Ma Jun, Li Juan, Liang Yingmin, Wang Jianmin, Li Yan, Yu Kang, Hu Jianda, Jin Jie, Wang Chun, Wu Depei, Xiao Yang, Huang Xiaojun

机构信息

From the Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (LW, JH); Peking University Institute of Hematology, Peking University, People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing (YS, XH); The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou (HH, JJ); Shanghai Children's Medical Center, Shanghai (JC); Jiangsu Province Hospital, Nanjing (JL); Harbin Hematologic Tumor Institution, Harbin (JM); The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou (JL); Tangdu Hospital, Fourth Military Medical University, Xi'an (YL); Changhai Hospital of the Second Military Medical University, Shanghai (JW); The First Affiliated Hospital of China Medical University, Shengyang (YL); The First Affiliated Hospital of Wenzhou Medical College, Wenzhou (KY); Fujian Medical University Union Hospital, Fuzhou (JH); The First People's Hospital of Shanghai, Shanghai (CW); The First Affiliated Hospital of Soochow University, Suzhou (DW); and The General Hospital of Guangzhou Military Command of PLA, Guangzhou, People's Republic of China (YX).

出版信息

Medicine (Baltimore). 2016 Jan;95(4):e2560. doi: 10.1097/MD.0000000000002560.

Abstract

Invasive fungal infection (IFI) remains as a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML). Here, we report the subgroup analysis of China Assessment of Antifungal Therapy in Haematological Disease (CAESAR) study to evaluate the risk of IFI in patients with AML in 1st remission receiving high-dose cytarabine (HiDAC) as consolidation. A total of 638 patients with AML in 1st complete remission were selected from the database. Among them, 130 patients received HiDAC alone with total dose of 2-3 g/m(2) × 6 while 508 patients received multiple-agent combination chemotherapy (multiagent chemo group). The patients' characteristics were generally not different but more patients in HiDAC group had peripherally inserted central catheter (61.5% vs 44.5%, P = 0.002). The median duration of neutropenia was 8.0 days in both HiDAC (2-20) and multiagent chemo group (2-28). Number of patients with prolonged neutropenia (>14 days) tended to be more in multiagent chemo group but not significant different (16.3% vs 8.8%, respectively). There was no significant difference between 2 groups in persistent neutropenic fever (40.8% vs 33.1%), antifungal treatment (11.5% vs 11.4%), and incidence of proven/probable IFI (4 probable in HiDAC vs 1 proven/4 probable in multiagent chemo, P = 0.35) or possible IFI. As to the clinical outcome in terms of duration of hospitalization and death in remission, there was a trend of shorter duration of hospitalization in HiDAC (19 days, 3-70) compare to multiagent chemo group (21 days, 1-367, P = 0.057) while no death documented in HiDAC group and only 2 patients died in the multiagent chemo group (0.4%). As to risk factors associated with IFI in all 638 patients, there was a trend of more IFI in patients with severe neutropenia (3.0%, P = 0.089) and previous history of IFI (3.85%, P = 0.086) while the antifungal prophylaxis was not associated significantly reduced IFI. Overall, our data support the perception that HiDAC alone as consolidation in first remission AML patients was well tolerated and not associated with increased hematological toxicity and IFI than conventional combination chemotherapy. Antifungal prophylaxis may not necessary except for patients with previous history of IFI.

摘要

侵袭性真菌感染(IFI)仍然是急性髓系白血病(AML)患者发病和死亡的重要原因。在此,我们报告血液病抗真菌治疗中国评估(CAESAR)研究的亚组分析,以评估首次缓解期接受大剂量阿糖胞苷(HiDAC)巩固治疗的AML患者发生IFI的风险。从数据库中选取了638例首次完全缓解的AML患者。其中,130例患者单独接受HiDAC治疗,总剂量为2 - 3g/m²×6,而508例患者接受多药联合化疗(多药化疗组)。患者的特征总体无差异,但HiDAC组更多患者留置了外周中心静脉导管(61.5%对44.5%,P = 0.002)。HiDAC组(2 - 20天)和多药化疗组(2 - 28天)的中性粒细胞减少中位持续时间均为8.0天。多药化疗组中性粒细胞减少持续时间延长(>14天)的患者数量倾向于更多,但差异无统计学意义(分别为16.3%对8.8%)。两组在持续性中性粒细胞减少性发热(40.8%对33.1%)、抗真菌治疗(11.5%对11.4%)以及确诊/疑似IFI的发生率(HiDAC组4例疑似,多药化疗组1例确诊/4例疑似,P = 0.35)或可能的IFI方面无显著差异。就住院时间和缓解期死亡的临床结局而言,HiDAC组的住院时间有短于多药化疗组的趋势(19天,3 - 70天),而多药化疗组为21天,1 - 367天,P = 0.057,HiDAC组无死亡记录,多药化疗组仅有2例患者死亡(0.4%)。对于所有638例患者中与IFI相关的危险因素,严重中性粒细胞减少患者(3.0%,P = 0.089)和既往有IFI病史的患者(3.85%,P = 0.086)发生IFI的趋势更高,而抗真菌预防与IFI显著降低无关。总体而言,我们的数据支持这样的观点,即首次缓解期AML患者单独使用HiDAC巩固治疗耐受性良好,与传统联合化疗相比,血液学毒性和IFI并未增加。除既往有IFI病史的患者外,可能无需进行抗真菌预防。

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