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2020年异基因造血细胞移植受者的侵袭性霉菌感染:我们是否取得了足够的进展?

Invasive Mold Infections in Allogeneic Hematopoietic Cell Transplant Recipients in 2020: Have We Made Enough Progress?

作者信息

Roth Romain Samuel, Masouridi-Levrat Stavroula, Chalandon Yves, Mamez Anne-Claire, Giannotti Federica, Riat Arnaud, Fischer Adrien, Poncet Antoine, Glampedakis Emmanouil, Van Delden Christian, Kaiser Laurent, Neofytos Dionysios

机构信息

Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.

Bone Marrow Transplant Unit, Division of Hematology, University Hospital of Geneva, and Faculty of Medicine, University of Geneva, Geneva, Switzerland.

出版信息

Open Forum Infect Dis. 2021 Nov 29;9(1):ofab596. doi: 10.1093/ofid/ofab596. eCollection 2022 Jan.

Abstract

BACKGROUND

Despite progress in diagnostic, prevention, and treatment strategies, invasive mold infections (IMIs) remain the leading cause of mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients.

METHODS

We describe the incidence, risk factors, and mortality of allo-HCT recipients with proven/probable IMI in a retrospective single-center 10-year (01/01/2010-01/01/2020) cohort study.

RESULTS

Among 515 allo-HCT recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%), and other molds (8/51, 15%). Overall, 35/51 (68.6%) breakthrough IMIs (bIMIs) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31-180, and >180 days post-HCT, respectively. Risk factors for IMI included prior allo-HCT (sub hazard ratio [SHR], 4.06;  = .004) and grade ≥2 acute graft-vs-host disease (aGvHD; SHR, 3.52;  < .001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI ( = .02). Mortality predictors included disease relapse (hazard ratio [HR], 7.47;  < .001), aGvHD (HR, 1.51;  = .001), CMV serology-positive recipients (HR, 1.47;  = .03), and IMI (HR, 3.94;  < .001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (log-rank = .47). At 1 year post-IMI diagnosis, 70.8% (34/48) of the patients were dead.

CONCLUSIONS

IA mortality has remained relatively unchanged during the last 2 decades. More than two-thirds of allo-HCT recipients with IMI die by 1 year post-IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.

摘要

背景

尽管在诊断、预防和治疗策略方面取得了进展,但侵袭性霉菌感染(IMIs)仍然是异基因造血细胞移植(allo-HCT)受者死亡的主要原因。

方法

在一项回顾性单中心10年(2010年1月1日至2020年1月1日)队列研究中,我们描述了确诊/疑似IMI的allo-HCT受者的发病率、危险因素和死亡率。

结果

在515例allo-HCT受者中,48例(9.3%)患者发生了51例确诊/疑似IMI:侵袭性曲霉病(IA;34/51,67%)、毛霉病(9/51,18%)和其他霉菌感染(8/51,15%)。总体而言,共识别出35/51(68.6%)例突破性IMI(bIMIs):22/35(62.8%)例IA和13/35(37.1%)例非IA IMI。IMI的1年累积发病率为7%:IA和非IA IMI分别为4.9%和2.1%。分别有14例(29.2%)、10例(20.8%)和24例(50.0%)患者在allo-HCT术后的前30天、31-180天和>180天被诊断出IMI。IMI的危险因素包括既往allo-HCT(亚风险比[SHR],4.06;P = 0.004)和≥2级急性移植物抗宿主病(aGvHD;SHR,3.52;P < 0.001)。全因1年死亡率为33%(170/515):发生IMI和未发生IMI的患者分别为48%(23/48)和31.5%(147/467)(P = 0.02)。死亡预测因素包括疾病复发(风险比[HR],7.47;P < 0.001)、aGvHD(HR,1.51;P = 0.001)、巨细胞病毒血清学阳性受者(HR,1.47;P = 0.03)和IMI(HR,3.94;P < 0.001)。发生IMI患者的全因12周死亡率为35.4%(17/48):IA为31.3%(10/32),非IA IMI为43.8%(7/16)(对数秩检验P = 0.47)。在IMI诊断后1年,70.8%(34/48)的患者死亡。

结论

在过去20年中,IA死亡率相对保持不变。超过三分之二发生IMI的allo-HCT受者在IMI诊断后1年内死亡。需要进行专门的强化研究以进一步改善临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d88a/8719608/fb150a7e5042/ofab596_fig1.jpg

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