泊沙康唑在异基因造血干细胞移植期间预防侵袭性真菌病的效果和安全性: 单中心回顾性分析

张艳芳; 娄世峰; 陈姝; 周慷; 罗云; 黄曦; 邓建川

doi:10.16016/j.1000-5404.202108062

您当前的位置：

首页 >

文章列表页 >

泊沙康唑在异基因造血干细胞移植期间预防侵袭性真菌病的效果和安全性: 单中心回顾性分析

专题报道：造血干细胞移植并发症的基础与临床研究 | 更新时间：2026-02-13

- 泊沙康唑在异基因造血干细胞移植期间预防侵袭性真菌病的效果和安全性: 单中心回顾性分析
- Efficacy and safety of posaconazole in prevention of invasive fungal infections during allogeneic hematopoietic stem cell transplantation: a single-center retrospective analysis
- 第三军医大学学报 2021年43卷第21期页码：2307-2312
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院血液内科
- 作者简介：
  
  [邓建川，E-mail: dengjccq@hospital.cqmu.edu.cn DENG Jianchuan, E-mail: dengjccq@hospital.cqmu.edu.cn
- 基金信息：
- DOI：10.16016/j.1000-5404.202108062
  中图分类号： R519;R617;R978.5
- 收稿：2021-08-10，
  
  修回：2021-09-01，
  
  纸质出版：2021-11-15
- 稿件说明：
移动端阅览
张艳芳, 娄世峰, 陈姝, 等. 泊沙康唑在异基因造血干细胞移植期间预防侵袭性真菌病的效果和安全性: 单中心回顾性分析[J]. 第三军医大学学报, 2021,43(21):2307-2312.

Yanfang ZHANG, Shifeng LOU, Shu CHEN, et al. Efficacy and safety of posaconazole in prevention of invasive fungal infections during allogeneic hematopoietic stem cell transplantation: a single-center retrospective analysis[J]. Journal of Third Military Medical University, 2021, 43(21): 2307-2312.
张艳芳, 娄世峰, 陈姝, 等. 泊沙康唑在异基因造血干细胞移植期间预防侵袭性真菌病的效果和安全性: 单中心回顾性分析[J]. 第三军医大学学报, 2021,43(21):2307-2312. DOI： 10.16016/j.1000-5404.202108062.

Yanfang ZHANG, Shifeng LOU, Shu CHEN, et al. Efficacy and safety of posaconazole in prevention of invasive fungal infections during allogeneic hematopoietic stem cell transplantation: a single-center retrospective analysis[J]. Journal of Third Military Medical University, 2021, 43(21): 2307-2312. DOI： 10.16016/j.1000-5404.202108062.

摘要

目的

探讨泊沙康唑(posaconazole，PCZ)在异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation

allo-HSCT)期间预防侵袭性真菌病(invasive fungal disease

IFD)的效果和安全性。

方法

回顾性分析2017年3月至2021年3月本院进行allo-HSCT的80例患者资料，观察移植期间接受泊沙康唑(泊沙康唑组，

=50)和同期接受其他抗真菌药物(对照组，

=30)预防IFD的效果和安全性。

结果

泊沙康唑组6例(12.0%)发生IFD，其中确诊2例，临床诊断4例。对照组14例(46.7%)发生IFD，其中确诊6例，临床诊断6例，拟诊2例。泊沙康唑组IFD发生率显著低于对照组(

=0.001)。泊沙康唑组一级预防38例，4例(10.5%)发生IFD；二级预防12例，2例(16.7%)发生IFD，一级预防和二级预防对IFD的发生差异无统计学意义(

=0.951)。泊沙康唑组IFD相关病死率显著低于对照组(21.0%

61.5%

=0.030)。不良反应方面，泊沙康唑组肝功异常明显少于对照组(20%

46.7%

=0.012)。

结论

泊沙康唑能更有效地预防allo-HSCT过程中IFD的发生，减少IFD相关死亡，不良反应更少。

Abstract

Objective

To investigate the efficacy and safety of posaconazole (PCZ) in the prevention of invasive fungal disease (IFD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods

The medical records of 80 patients who received allo-HSCT at our center from March 2017 to March 2021 were retrospectively reviewed and analyzed. They were accordingly divided into PCZ group (

=50) and control group (

=30

taking other anti-fungal drugs). The efficacy and safety of PCZ was analyzed in the prevention of IFD.

Results

In the PCZ group

6 patients (12.0%) developed IFD

including 2 confirmed cases and 4 clinically diagnosed. While

IFD occurred in 14 cases from the control group

including 6 confirmed

6 clinically diagnosed and 2 suspected cases. The incidence of IFD was significantly lower in the PCZ group than the control group (

=0.001). Moreover

in the PCZ group

38 patients (10.5%) with primary prevention developed 4 cases of IFD

and 2 cases (16.7%) of IFD occurred in 12 patients of secondary prevention

showing no significant difference in the IFD incidence (

=0.951). The IFD-related mortality (21.0%

61.5%

=0.030) and rate of abnormal liver function (20.0%

46.7%

=0.012) were both significantly lower in the PCZ group than the control group.

Conclusion

PCZ is effective in the prevention of IFD during allo-HSCT

and reduces IFD-related deaths and occurrence of adverse reactions.

关键词

Keywords

references

JENKS J D, CORNELY O A, CHEN S C, et al . Breakthrough invasive fungal infections: Who is at risk? [J ] . Mycoses, 2020, 63(10): 1021-1032. DOI: 10.1111/myc.13148.

NEOFYTOS D, HORN D, ANAISSIE E, et al . Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of multicenter prospective antifungaltherapy (PATH) alliance registry[J ] . Clin Infect Dis, 2009, 48(3): 265-273. DOI: 10.1086/595846.

WINSTON D J, BARTONI K, TERRITO M C, et al . Efficacy, safety, and breakthrough infections associated with standard long-term posaconazole antifungal prophylaxis in allogeneic stem cell transplantation recipients[J ] . Biol Blood Marrow Transplant, 2011, 17(4): 507-515. DOI: 10.1016/j.bbmt.2010.04.017.

LIONAKIS M S, LEWIS R E, KONTOYIANNIS D P. Breakthrough invasive mold infections in the hematology patient: current concepts and future directions[J]. Clin Infect Dis, 2018, 67(10): 1621-1630. DOI: 10.1093/cid/ciy473.

MARR K A, CRIPPA F, LEISENRING W, et al . Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants[J ] . Blood, 2004, 103(4): 1527-1533. DOI: 10.1182/blood-2003-08-2644.

WINSTON D J, EMMANOUILIDES C, BARTONI K, et al . Elimination of Aspergillus infection in allogeneic stem cell transplant recipients with long-term itraconazole prophylaxis: prevention is better than treatment[J ] . Blood, 2004, 104(5): 1581. DOI: 10.1182/blood-2004-03-1025.

ROTHE A, CLAßEN A, CARNEY J, et al . Bridging antifungal prophylaxis with 50 mg or 100 mg micafungin in allogeneic stem cell transplantation: a retrospective analysis[J ] . Eur J Haematol, 2020, 104(4): 291-298. DOI: 10.1111/ejh.13372.

HOF H. A new, broad-spectrum azole antifungal: posaconazole: mechanisms of action and resistance, spectrum of activity[J]. Mycoses, 2006, 49(Suppl 1): 2-6. DOI: 10.1111/j.1439-0507.2006.01295.x.

MEHTA A K, LANGSTON A A. Use of posaconazole in the treatment of invasive fungal infections[J]. Expert Rev Hematol, 2009, 2(6): 619-630. DOI: 10.1586/ehm.09.46.

CHEN L, KREKELS E H J, VERWEIJ P E, et al . Pharmacokinetics and pharmacodynamics of posaconazole[J ] . Drugs, 2020, 80(7): 671-695. DOI: 10.1007/s40265-020-01306 -y.

CORNELY O A, MAERTENS J, WINSTON D J, et al . Posaconazole vs . fluconazole or itraconazole prophylaxis in patients with neutropenia[J ] . N Engl J Med, 2007, 356(4): 348-359. DOI: 10.1056/nejmoa061094..

PAGANO L, CAIRA M, CANDONI A, et al . Evaluation of the practice of antifungal prophylaxis use in patients with newly diagnosed acute myeloid leukemia: results from the SEIFEM 2010-B registry[J ] . Clin Infect Dis, 2012, 55(11): 1515-1521. DOI: 10.1093/cid/cis773.

KRALJEVIC M, KHANNA N, MEDINGER M, et al . Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients[J ] . Med Mycol, 2021, 59(7): 701-711. DOI: 10.1093/mmy/myaa106.

SANSONE-PARSONS A, KRISHNA G, MARTINHO M, et al . Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus[J ] . Pharmacotherapy, 2007, 27(6): 825-834. DOI: 10.1592/phco.27.6.825.

COLLINS J, SHEA K, PARSAD S, et al . The impact of initiating posaconazole on tacrolimus pharmacokinetics in allogene ic stem cell transplantation[J ] . J Oncol Pharm Pract, 2020, 26(1): 5-12. DOI: 10.1177/1078155219833440.

WONG T Y, LOO Y S, VEETTIL S K, et al . Efficacy and safety of posaconazole for the prevention of invasive fungal infections in immunocompromised patients: a systematic review with meta-analysis and trial sequential analysis[J ] . Sci Rep, 2020, 10(1): 14575. DOI: 10.1038/s41598-020-71571-0.

中国医师协会血液科医师分会, 中国侵袭性真菌感染工作组. 血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则(第六次修订版) [J]. 中华内科杂志, 2020, 59(10): 754-763. DOI: 10.3760/cma.j.cn112138-20200627-00624.

Hematologist Branch of Chinese Medical Doctor Association, Chinese Working Group on Invasive fungal infection. Diagnostic criteria and principles of treatment for invasive mycosis in patients with hematologic diseases/malignancies (6th Revision)[J]. Chin J Internal Med, 2020, 59(10): 754-763. DOI: 10.3760/cma.j.cn112138-20200627-00624.

CHEN A P, SETSER A, ANADKAT M J, et al . Grading dermatologic adverse events of cancer treatments: The Common Terminology Criteria for Adverse Events Version 4.0[J ] . J Am Acad Dermatol, 2012, 67(5): 1025-1039. DOI: 10.1016/j.jaad.2012.02.010.

VAN DAELE R, SPRIET I, MAERTENS J. Posaconazole in prophylaxis and treatment of invasive fungal infections: a pharmacokinetic, pharmacodynamic and clinical evaluation[J]. Expert Opin Drug Metab Toxicol, 2020, 16(7): 539-550. DOI: 10.1080/17425255.2020.1764939.

TANG J L, KUNG H C, LEI W C, et al . High incidences of invasive fungal infections in acute myeloid leukemia patients receiving induction chemotherapy without systemic antifungal prophylaxis: a prospective observational study in Taiwan[J ] . PLoS ONE, 2015, 10(6): e0128410. DOI: 10.1371/journal.pone.0128410.

XU X H, ZHANG L, CAO X X, et al . Evaluation of the implementation rate of primary antifungal prophylaxis and the prognosis of invasive fungal disease in acute leukemia patients in China[J ] .J Infect Chemother, 2017, 23(6): 360-367. DOI: 10.1016/j.jiac.2017.02.011.

BERKING S, DOEDENS D, HORNS H, et al . Antifungal prophylaxis in newly diagnosed AML patients—Adherence to guidelines and feasibility in a real life setting[J ] . Mycoses, 2017, 60(9): 600-606. DOI: 10.1111/myc.12635.

ÖZKOCAMAN V, ÖZKALEMKAȘ F, SEYHAN S, et al . The outcome of antifungal prophylaxis with posaconazole in patients with acute myeloid leukemia: a single-center study[J ] . Turk J Haematol, 2018, 35(4): 277-282. DOI: 10.4274/tjh.2017.0430.

BUSCA A, CANDONI A, AUDISIO E, et al . Long-lasting protective effect of posaconazole prophylaxis in patients with acute myeloid leukemia receiving allogeneic hematopoietic stem cell transplantation[J ] . Biol Blood Marrow Transplant, 2016, 22(12): 2214-2219. DOI: 10.1016/j.bbmt.2016.09.019.

LI W, XIA F, ZHOU H, et al . Efficacy of posaconazole prophylaxis for fungal disease in hematology patients treated with chemotherapy and transplantation: an open-label, prospective, observational study[J ] . Front Microbiol, 2020, 11: 349. DOI: 10.3389/fmicb.2020.00349.

SCHRENK K G, SCHNETZKE U, STEGEMANN K, et al . Efficacy of antifungal prophylaxis with oral suspension posaconazole during induction chemotherapy of acute myeloid leukemia[J ] . J Cancer Res Clin Oncol, 2015, 141(9): 1661-1668. DOI: 10.1007/s00432-015-1962-x.

GIRMENIA C, MICOZZI A, PICIOCCHI A, et al . Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia[J ] . Leuk Res, 2014, 38(4): 469-474. DOI: 10.1016/j.leukres.2014.01.007.

KRISHNA G, MOTON A, MA L, et al . Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers[J ] . Antimicrob Agents Chemother, 2009, 53(3): 958-966. DOI: 10.1128/aac.01034-08.

CHAYAKULKEEREE M, POOVIPIROM N, SIENGWATTANA P, et al . Effect of proton pump inhibitor on plasma voriconazole concentration in thai patients[J ] . J Med Assoc Thai, 2015, 98(3): 232-237.

CHO S Y, LEE D G, CHOI S M, et al . Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single-centre retrospective study in korea and clinical considerations[J ] . Mycoses, 2015, 58(9): 565-571. DOI: 10.1111/myc.12357.

AUBERGER J, LASS-FLÖRL C, AIGNER M, et al . Invasive fungal breakthrough infections, fungal colonization and emergence of resistant strains in high-risk patients receiving antifungal prophylaxis with posaconazole: real-life data from a single-centre institutional retrospective observational study[J ] . J Antimicrob Chemother, 2012, 67(9): 2268-2273. DOI: 10.1093/jac/dks189.

BOSE P, PAREKH H D, HOLTER J L, et al . Disseminated fusariosis occurring in two patients despite posaconazole prophylaxis[J ] . J Clin Microbiol, 2011, 49( 4): 1674-1675. DOI: 10.1128/jcm.02325-10.

LECLERC E, COMBAREL D, UZUNOV M, et al . Prevention of invasive Aspergillus fungal infections with the suspension and delayed-release tablet formulations of posaconazole in patients with haematologic malignancies[J ] . Sci Rep, 2018, 8(1): 1681. DOI: 10.1038/s41598-018-20136-3.

FU C C, CHEN J, XU Y, et al . Dose adjustment of immunosuppressants during co-administration of posaconazole: a systematic review[J ] . Clin Investig Med, 2018, 41(1): E5-E15. DOI: 10.25011/cim.v41i1.29458.

徐宵寒, 张路, 段明辉. 评价泊沙康唑预防血液系统疾病患者粒细胞缺乏期侵袭性真菌病的效果[J]. 中国感染控制杂志, 2017, 16(1): 32-35, 57.

XU X H, ZHANG L, DUAN M H. Efficacy of posaconazole in preventing invasive fungal disease in hematologic patients with neutropenia[J]. Chin J Infect Control, 2017, 16(1): 32-35, 57.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

新药时代下如何为异基因造血干细胞移植赋能

祛铁治疗改善恶性血液病患者造血干细胞移植后造血功能的临床分析

西罗莫司和伊马替尼治疗激素难治性慢性移植物抗宿主病的临床观察: 一项单中心回顾性分析

人脐带间充质干细胞预防小鼠急性移植物抗宿主病作用及其机制研究

慢性移植物抗宿主病患者免疫细胞亚群分选的表面标志组合策略