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异基因造血干细胞移植后早期 COVID-19 的高死亡率:德国合作移植研究组的回顾性多中心分析。

High Mortality of COVID-19 Early after Allogeneic Stem Cell Transplantation: A Retrospective Multicenter Analysis on Behalf of the German Cooperative Transplant Study Group.

机构信息

Department of Internal Medicine IV - Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.

出版信息

Transplant Cell Ther. 2022 Jun;28(6):337.e1-337.e10. doi: 10.1016/j.jtct.2022.03.010. Epub 2022 Mar 13.

Abstract

Recipients of allogeneic stem cell transplantation (alloSCT) are at high risk for contracting infectious diseases with high morbidity and mortality. Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that can lead to severe pneumonia and acute respiratory distress syndrome, with a potentially fatal outcome. In this retrospective study conducted on behalf of the German Cooperative Transplant Study Group, we aimed to analyze risk factors, disease course, and outcomes of COVID-19 in patients who underwent alloSCT. AlloSCT recipients who became infected with SARS-CoV-2 at German and Austrian transplant centers between February 2020 and July 2021 were included. Classification of COVID-19 severity into mild, moderate-severe, or critical disease and division of the course of the pandemic into 4 phases were done according to the German Robert Koch Institute. The main endpoint was overall mortality at the end of follow-up. We further analyzed the need for treatment in an intensive care unit (ICU) and the severity of disease. Risk factors were evaluated using univariate and multivariate analyses, and survival analysis was performed using Kaplan-Meier method. The study cohort comprised 130 patients from 14 transplant centers, with a median age at diagnosis of COVID-19 of 59 years (range, 20 to 81 years) and a median interval between alloSCT and COVID-19 of 787 days (range, 19 to 8138 days). The most common underlying diseases were acute myeloid leukemia (45.4%) and lymphoma (10.8%). The majority of patients (84.9%) were infected in the later phases of the pandemic; 20.8% had moderate-severe disease, 12.3% had critical disease, and 19.2% were treated in an ICU. After a median follow-up of 127 days, overall mortality was 16.2%, 52.0% among patients treated in an ICU. Risk factors for mortality in multivariate analysis were active disease (odds ratio [OR], 4.46), infection with SARS-CoV-2 ≤365 days after alloSCT (OR, 5.60), age >60 years (OR, 5.39), and ongoing immunosuppression with cyclosporine (OR, 8.55). Risk factors for developing moderate-severe or critical disease were concurrent immunosuppression (OR, 4.06) and age >40 years (OR, 4.08). Patients after alloSCT exhibit a substantially increased mortality risk after COVID-19 infection compared with the normal population, without considerable improvement over the course of the pandemic. Risk factors include age, early infection post-alloSCT, and active immunosuppression. Further studies are needed to improve prevention and treatment in this high-risk patient group.

摘要

异基因造血干细胞移植(alloSCT)受者罹患传染性疾病的风险很高,这些疾病具有较高的发病率和死亡率。2019 年冠状病毒病(COVID-19)是一种病毒性呼吸道疾病,可导致严重肺炎和急性呼吸窘迫综合征,具有潜在的致命结局。在这项代表德国合作移植研究组进行的回顾性研究中,我们旨在分析 alloSCT 受者 COVID-19 的风险因素、疾病进程和结局。该研究纳入了 2020 年 2 月至 2021 年 7 月期间在德国和奥地利移植中心感染 SARS-CoV-2 的 alloSCT 受者。根据德国罗伯特·科赫研究所(Robert Koch Institute)的分类,将 COVID-19 严重程度分为轻症、中重度或重症,并将大流行过程分为 4 个阶段。主要终点是随访结束时的总死亡率。我们进一步分析了需要在重症监护病房(ICU)治疗的情况和疾病严重程度。使用单变量和多变量分析评估了风险因素,并使用 Kaplan-Meier 方法进行了生存分析。该研究队列包括来自 14 个移植中心的 130 名患者,诊断 COVID-19 时的中位年龄为 59 岁(范围,20 至 81 岁),alloSCT 与 COVID-19 之间的中位间隔为 787 天(范围,19 至 8138 天)。最常见的基础疾病是急性髓细胞白血病(45.4%)和淋巴瘤(10.8%)。大多数患者(84.9%)在大流行的后期阶段感染;20.8%为中重度疾病,12.3%为重症疾病,19.2%在 ICU 接受治疗。中位随访 127 天后,总死亡率为 16.2%,在 ICU 接受治疗的患者死亡率为 52.0%。多变量分析中死亡的危险因素为疾病活动(比值比[OR],4.46)、alloSCT 后≤365 天感染 SARS-CoV-2(OR,5.60)、年龄>60 岁(OR,5.39)和持续环孢素免疫抑制(OR,8.55)。发展为中重度或重症疾病的危险因素是同时存在免疫抑制(OR,4.06)和年龄>40 岁(OR,4.08)。与普通人群相比,alloSCT 后患者在感染 COVID-19 后死亡率显著增加,而且在大流行期间并没有明显改善。风险因素包括年龄、 alloSCT 后早期感染和活跃的免疫抑制。需要进一步研究以改善这一高危患者群体的预防和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b56/8918088/07f28f0252d9/gr1_lrg.jpg

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