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异基因造血细胞移植后与细胞因子释放综合征相关的侵袭性酵母感染。

Invasive Yeast Infection after Haploidentical Donor Hematopoietic Cell Transplantation Associated with Cytokine Release Syndrome.

机构信息

Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Stem Cell Transplant and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts.

Harvard Medical School, Boston, Massachusetts; Stem Cell Transplant and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts.

出版信息

Transplant Cell Ther. 2022 Aug;28(8):508.e1-508.e8. doi: 10.1016/j.jtct.2022.04.023. Epub 2022 May 6.

Abstract

The use of haploidentical donor hematopoietic cell transplantation (haploHCT) has expanded, but recent reports raise concern for increased rates of infectious complications. The incidence and risk factors for invasive fungal disease (IFD) after haploHCT have not been well elucidated. This study aimed to evaluate the incidence and risk factors for IFD after haploHCT. The identification of key risk factors will permit targeted prevention measures and may explain elevated risk for other infectious complications after haploHCT. This single-center retrospective study included all adults undergoing haploHCT between May 2011 and May 2021 (n = 205). The 30-day and 1-year cumulative incidences of proven or probable IFD and 1-year nonrelapse mortality (NRM) were assessed. Secondary analyses evaluated risk factors for invasive yeast infection (IYI) using univariate and multivariable Cox regression models. Twenty-nine patients (14%) developed IFD following haploHCT. Nineteen (9.3%) developed IYI in the first year, 13 of which occurred early, with a 30-day cumulative incidence of 6.3% (95% confidence interval [CI], 2.9% to 9.6%) and increased NRM in patients with IYI (53.9% versus 10.9%). The majority of yeast isolates (17 of 20; 85%) were fluconazole- susceptible. The incidence of IYI in the first 30 days after haploHCT was 10% in the 110 patients (54%) who developed cytokine release syndrome (CRS) and 21% in the 29 patients (14%) who received tocilizumab. On multivariable analysis, acute myelogenous leukemia (hazard ratio [HR], 6.24; 95% CI, 1.66 to 23.37; P = .007) and CRS (HR, 4.65; 95% CI, 1.00 to 21.58; P = .049) were associated with an increased risk of early IYI after haploHCT. CRS after haploHCT is common and is associated with increased risk of early IYI. The identification of CRS as a risk factor for IYI raises questions about its potential association with other infections after haploHCT. Recognition of key risk factors for infection may permit the development of individualized strategies for prevention and intervention and minimize potential side effects.

摘要

单倍体相合供者造血细胞移植(haploHCT)的应用已经扩大,但最近的报告引起了人们对感染并发症发生率增加的关注。haploHCT 后侵袭性真菌病(IFD)的发生率和危险因素尚未得到很好的阐明。本研究旨在评估 haploHCT 后 IFD 的发生率和危险因素。确定关键的危险因素将允许有针对性的预防措施,并可能解释 haploHCT 后其他感染并发症的高风险。这项单中心回顾性研究纳入了 2011 年 5 月至 2021 年 5 月期间接受 haploHCT 的所有成年人(n=205)。评估了 haploHCT 后 30 天和 1 年累积确诊或可能 IFD 的发生率和 1 年非复发死亡率(NRM)。次要分析使用单变量和多变量 Cox 回归模型评估了侵袭性酵母感染(IYI)的危险因素。29 例患者(14%)在 haploHCT 后发生 IFD。19 例(9.3%)在第 1 年发生 IYI,其中 13 例发生在早期,30 天累积发生率为 6.3%(95%置信区间[CI],2.9%至 9.6%),并伴有 IYI 患者的 NRM 增加(53.9%对 10.9%)。大多数酵母分离株(20 株中的 17 株;85%)对氟康唑敏感。在 110 例发生细胞因子释放综合征(CRS)的患者(54%)和 29 例接受托珠单抗治疗的患者(14%)中,CRS 后 30 天内 IYI 的发生率为 10%。多变量分析显示,急性髓细胞白血病(HR,6.24;95%CI,1.66 至 23.37;P=0.007)和 CRS(HR,4.65;95%CI,1.00 至 21.58;P=0.049)与 haploHCT 后早期 IYI 的风险增加相关。HaploHCT 后 CRS 很常见,与早期 IYI 的风险增加有关。将 CRS 确定为 IYI 的危险因素提出了其与 haploHCT 后其他感染潜在关联的问题。识别感染的关键危险因素可能允许制定个性化的预防和干预策略,并最大限度地减少潜在的副作用。

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