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首次和第二次异基因造血细胞移植后植入前血流感染的发生率、病因、危险因素和结局。

Incidence, etiology, risk factors, and outcomes of pre-engraftment bloodstream infections after first and second allogeneic hematopoietic cell transplantation.

机构信息

Department of Bone Marrow Transplantation, National Research Center for Hematology, Moscow, Russia.

Laboratory of Microbiology, Mycology and Antibacterial Therapy, National Research Center for Hematology, Moscow, Russia.

出版信息

Transpl Infect Dis. 2022 Jun;24(3):e13842. doi: 10.1111/tid.13842. Epub 2022 May 9.

DOI:10.1111/tid.13842
PMID:35501664
Abstract

INTRODUCTION

With an increasing number of allogeneic hematopoietic cell transplantations (allo-HCT) bloodstream infections (BSI) are still among the most common and serious complications. This study aimed to analyze the incidence, etiology, risk factors, and outcomes of pre-engraftment BSI after the first and the second allo-HCT.

MATERIALS AND METHODS

This is a retrospective study of 284 patients who underwent the first allo-HCT and 37 patients after the second allo-HCT at the National Research Center for Hematology in Moscow, Russia, from January 2018 till September 2021.

RESULTS

Cumulative incidence of pre-engraftment BSI was 29.9% after the first allo-HCT and 35.1% after the second (p = .805). The median time to the first BSI was 9 days (range 0-61 days) after the first and 16 days (range 1-28 days) after the second allo-HCT (p = .014). A total of 113 pathogens were isolated during 94 BSI episodes after the first allo-HCT (gram-negative bacteria 52.2%; gram-positive bacteria 47.7%). Fourteen pathogens were isolated during 14 BSI episodes after the second allo-HCT (gram-negative bacteria 50.0%; gram-positive bacteria 50.0%). The only significant difference was found in the rate of carbapenem-resistant gram-negative bacteria, which was higher after the second allo-HCT compared to the first (57.1% vs. 13.6%; p = .048). Mismatched unrelated donor (hazards ratio [HR] 3.01; 95% confidence interval [CI]: 1.62-5.60; p < .0001) and haploidentical donor transplantations (HR 1.84; 95% CI: 1.02-3.33; p = .042) were the only independent risk factors associated with the higher risk of pre-engraftment BSI. Overall 30-day survival after all BSI episodes was 94.4%. Survival was lower after BSI during the second allo-HCT compared to the first (71.4% vs. 97.9%; p < .0001), particularly after BSI was caused by carbapenem-resistant gram-negative bacteria (25.0% vs. 100.0%; p = .0023). The non-relapse mortality rate at day +60 was 4.0%, and the risk was highly associated with primary graft failure (HR 9.62; 95% CI: 1.33-71.43), second allo-HCT (HR 6.80; 95% CI: 1.36-34.48), and pre-engraftment BSI caused by carbapenem-resistant gram-negative bacteria (HR 32.11; 95% CI: 4.91-210.15).

CONCLUSIONS

Pre-engraftment BSI is still a common complication after allo-HCT, particularly after mismatched unrelated and haploidentical donor transplantations. BSI incidence was slightly higher after the second allo-HCT with a significantly higher rate of carbapenem-resistant BSI. Although pre-engraftment BSI would generally follow a benign clinical course, survival was dramatically lower during the second allo-HCT, especially after carbapenem-resistant BSI.

摘要

简介

随着越来越多的异基因造血细胞移植(allo-HCT)后,血流感染(BSI)仍然是最常见和最严重的并发症之一。本研究旨在分析第一次和第二次 allo-HCT 后植入前 BSI 的发生率、病因、危险因素和结果。

材料和方法

这是一项回顾性研究,纳入了 2018 年 1 月至 2021 年 9 月在俄罗斯莫斯科国家血液学研究中心接受第一次 allo-HCT 的 284 例患者和第二次 allo-HCT 后的 37 例患者。

结果

第一次 allo-HCT 后植入前 BSI 的累积发生率为 29.9%,第二次为 35.1%(p=0.805)。第一次 allo-HCT 后首次发生 BSI 的中位时间为 9 天(范围 0-61 天),第二次为 16 天(范围 1-28 天)(p=0.014)。第一次 allo-HCT 后共分离出 94 例 BSI 发作中的 113 种病原体(革兰氏阴性菌 52.2%;革兰氏阳性菌 47.7%)。第二次 allo-HCT 后共分离出 14 例 BSI 发作中的 14 种病原体(革兰氏阴性菌 50.0%;革兰氏阳性菌 50.0%)。唯一显著的差异在于碳青霉烯类耐药革兰氏阴性菌的发生率,第二次 allo-HCT 明显高于第一次(57.1%比 13.6%;p=0.048)。不匹配的无关供体(风险比[HR]3.01;95%置信区间[CI]:1.62-5.60;p<0.0001)和单倍体相合供体移植(HR 1.84;95% CI:1.02-3.33;p=0.042)是与植入前 BSI 风险增加相关的唯一独立危险因素。所有 BSI 发作的 30 天总生存率为 94.4%。第二次 allo-HCT 后 BSI 的生存率明显低于第一次(71.4%比 97.9%;p<0.0001),尤其是由碳青霉烯类耐药革兰氏阴性菌引起的 BSI(25.0%比 100.0%;p=0.0023)。+60 天的非复发死亡率为 4.0%,风险与原发性移植物失败(HR 9.62;95% CI:1.33-71.43)、第二次 allo-HCT(HR 6.80;95% CI:1.36-34.48)和由碳青霉烯类耐药革兰氏阴性菌引起的植入前 BSI(HR 32.11;95% CI:4.91-210.15)高度相关。

结论

植入前 BSI 仍然是 allo-HCT 后的常见并发症,特别是在不匹配的无关供体和单倍体相合供体移植后。第二次 allo-HCT 后 BSI 的发生率略有增加,碳青霉烯类耐药 BSI 的发生率明显更高。虽然植入前 BSI 通常会出现良性临床病程,但第二次 allo-HCT 期间的生存率明显降低,尤其是在碳青霉烯类耐药 BSI 后。

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