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造血干细胞移植后接受伊曲康唑预防治疗的儿童和青少年患者中的侵袭性真菌病

Invasive Fungal Disease Among Pediatric and Adolescent Patients Undergoing Itraconazole Prophylaxis After Hematopoietic Stem Cell Transplantation.

作者信息

Itsaradisaikul Suluk, Pakakasama Samart, Boonsathorn Sophida, Techasaensiri Chonnamet, Rattanasiri Sasivimol, Apiwattanakul Nopporn

机构信息

Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pediatrics, Uttaradit Hospital, Uttaradit, Thailand.

Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Transplant Proc. 2021 Jul-Aug;53(6):2021-2028. doi: 10.1016/j.transproceed.2021.04.010. Epub 2021 May 14.

Abstract

BACKGROUND

Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Itraconazole has been used for prevention of IFD, but data related to incidence and associated factors of IFD in pediatric and adolescent patients on itraconazole prophylaxis remain scarce.

OBJECTIVES

To identify incidence and risk factors associated with IFD among pediatric and adolescent patients receiving itraconazole prophylaxis after HSCT.

METHODS

Patients younger than 21 years who received itraconazole prophylaxis after HSCT from January 2007 to December 2016 were retrospectively enrolled. Incidence of IFD within 1 year and associated factors were analyzed.

RESULTS

All patients received itraconazole during the pre-engraftment period. Of 170 patients, 29 had IFD, with an incidence of 17.1% at 1 year. IFD at 1 year was significantly associated with increased mortality. Of 29 patients with IFD, only 9 developed IFD while on itraconazole prophylaxis (5.3%), all of whom had invasive pulmonary aspergillosis. No invasive candidiasis occurred during itraconazole prophylaxis. Prolonged neutropenia (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.02-1.13), graft-versus-host disease within 100 days after transplantation (HR = 3.17; 95% CI, 1.17-8.57), and using etoposide in preconditioning regimens (HR = 21.60; 95% CI, 2.44-190.95) were significantly associated with IFD at 1 year. No patients had to discontinue itraconazole because of its adverse effects.

CONCLUSIONS

Itraconazole proffered good efficacy for prevention of candidiasis during the pre-engraftment period. Most IFD episodes occurred after the engraftment period when itraconazole had been discontinued. During this period, patients with risk factors require appropriate fungal prophylaxis.

摘要

背景

侵袭性真菌病(IFD)是造血干细胞移植(HSCT)患者发病和死亡的主要原因。伊曲康唑已被用于预防IFD,但关于接受伊曲康唑预防的儿童和青少年患者中IFD的发病率及相关因素的数据仍然匮乏。

目的

确定HSCT后接受伊曲康唑预防的儿童和青少年患者中IFD的发病率及相关危险因素。

方法

回顾性纳入2007年1月至2016年12月期间HSCT后接受伊曲康唑预防的21岁以下患者。分析1年内IFD的发病率及相关因素。

结果

所有患者在植入前期均接受了伊曲康唑治疗。170例患者中,29例发生IFD,1年发病率为17.1%。1年时发生IFD与死亡率增加显著相关。29例IFD患者中,仅9例在接受伊曲康唑预防治疗时发生IFD(5.3%),所有这些患者均患有侵袭性肺曲霉病。在伊曲康唑预防治疗期间未发生侵袭性念珠菌病。中性粒细胞减少持续时间延长(风险比[HR]=1.08;95%置信区间[CI],1.02-1.13)、移植后100天内发生移植物抗宿主病(HR=3.17;95%CI,1.17-8.57)以及在预处理方案中使用依托泊苷(HR=21.60;95%CI,2.44-190.95)与1年时的IFD显著相关。没有患者因伊曲康唑的不良反应而不得不停药。

结论

伊曲康唑在植入前期预防念珠菌病方面疗效良好。大多数IFD发作发生在植入期之后,此时伊曲康唑已停用。在此期间,具有危险因素的患者需要进行适当的真菌预防。

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