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儿童造血干细胞移植受者重症监护后的危重病风险及长期预后

Critical Illness Risk and Long-Term Outcomes Following Intensive Care in Pediatric Hematopoietic Cell Transplant Recipients.

作者信息

Zinter Matt S, Brazauskas Ruta, Strom Joelle, Chen Stella, Bo-Subait Stephanie, Sharma Akshay, Beitinjaneh Amer, Dimitrova Dimana, Guilcher Greg, Preussler Jaime, Myers Kasiani, Bhatt Neel S, Ringden Olle, Hematti Peiman, Hayashi Robert J, Patel Sagar, De Oliveira Satiro Nakamura, Rotz Seth, Badawy Sherif M, Nishihori Taiga, Buchbinder David, Hamilton Betty, Savani Bipin, Schoemans Hélène, Sorror Mohamed, Winestone Lena, Duncan Christine, Phelan Rachel, Dvorak Christopher C

机构信息

Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA.

Department of Pediatrics, Division of Allergy, Immunology, and BMT, University of California, San Francisco, San Francisco, CA, USA.

出版信息

medRxiv. 2023 Aug 5:2023.07.31.23293444. doi: 10.1101/2023.07.31.23293444.

Abstract

BACKGROUND

Allogeneic hematopoietic cell transplantation (HCT) can be complicated by the development of organ toxicity and infection necessitating intensive care. Risk factors for intensive care admission are unclear due to heterogeneity across centers, and long-term outcome data after intensive care are sparse due to a historical paucity of survivors.

METHODS

The Center for International Blood and Marrow Transplant Research (CIBMTR) was queried to identify patients age ≤21 years who underwent a 1 allogeneic HCT between 2008-2014 in the United States or Canada. Records were cross-referenced with the Virtual Pediatric Systems pediatric ICU database to identify intensive care admissions. CIBMTR follow-up data were collected through the year 2020.

RESULT

We identified 6,995 pediatric HCT patients from 69 HCT centers, of whom 1,067 required post-HCT intensive care. The cumulative incidence of PICU admission was 8.3% at day +100, 12.8% at 1 year, and 15.3% at 5 years post HCT. PICU admission was linked to younger age, lower median zip code income, Black or multiracial background, pre-transplant organ toxicity, pre-transplant CMV seropositivity, use of umbilical cord blood and/or HLA-mismatched allografts, and the development of post-HCT graft-versus-host disease or malignancy relapse. Among PICU patients, survival to ICU discharge was 85.7% but more than half of ICU survivors were readmitted to a PICU during the study interval. Overall survival from the time of 1 PICU admission was 52.5% at 1 year and 42.6% at 5 years. Long-term post-ICU survival was worse among patients with malignant disease (particularly if relapsed), as well as those with poor pre-transplant organ function and alloreactivity risk-factors. In a landmark analysis of all 1-year HCT survivors, those who required intensive care in the first year had 10% lower survival at 5 years (77.1% vs. 87.0%, p<0.001) and developed new dialysis-dependent renal failure at a greater rate (p<0.001).

CONCLUSIONS

Intensive care management is common in pediatric HCT patients. Survival to ICU discharge is high, but ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in many patients. Together, these data suggest an ongoing burden of toxicity in pediatric HCT patients that continues to limit long-term survival.

摘要

背景

异基因造血细胞移植(HCT)可能会并发器官毒性和感染,需要重症监护。由于各中心存在异质性,重症监护入院的危险因素尚不清楚,且由于历史上幸存者较少,重症监护后的长期结局数据也很稀少。

方法

查询国际血液和骨髓移植研究中心(CIBMTR),以确定2008年至2014年在美国或加拿大接受异基因HCT的年龄≤21岁的患者。将记录与虚拟儿科系统儿科重症监护病房数据库进行交叉核对,以确定重症监护入院情况。通过2020年收集CIBMTR随访数据。

结果

我们从69个HCT中心识别出6995例儿科HCT患者,其中1067例在HCT后需要重症监护。在HCT后第100天,儿科重症监护病房(PICU)入院的累积发生率为8.3%,1年时为12.8%,5年时为15.3%。PICU入院与年龄较小、邮政编码中位数收入较低、黑人或多种族背景、移植前器官毒性、移植前巨细胞病毒血清学阳性、使用脐带血和/或HLA不匹配的同种异体移植物以及HCT后移植物抗宿主病或恶性肿瘤复发有关。在PICU患者中,存活至ICU出院的比例为85.7%,但超过一半的ICU幸存者在研究期间再次入住PICU。从首次PICU入院时起,1年总生存率为52.5%,5年时为42.6%。恶性疾病患者(尤其是复发患者)以及移植前器官功能差和存在同种异体反应危险因素的患者,ICU后的长期生存率较差。在对所有1年HCT幸存者的一项标志性分析中,第一年需要重症监护的患者5年生存率低10%(77.1%对87.0%,p<0.001),且发生新的依赖透析的肾衰竭的比例更高(p<0.001)。

结论

重症监护管理在儿科HCT患者中很常见。存活至ICU出院的比例很高,但持续的并发症需要反复入住ICU,并导致许多患者1年结局不佳。总之,这些数据表明儿科HCT患者持续存在毒性负担,这继续限制着长期生存。

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