Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children

被引：41

作者：

Diorio, Caroline ^{[1
,2
]}

Shaw, Pamela A. ^{[3
]}

Pequignot, Edward ^{[4
]}

Orlenko, Alena ^{[3
]}

Chen, Fang ^{[4
,5
,6
]}

Aplenc, Richard ^{[1
,2
,5
]}

Barrett, David M. ^{[1
,2
]}

Bassiri, Hamid ^{[7
]}

Behrens, Edward ^{[2
,8
]}

DiNofia, Amanda M. ^{[1
,2
]}

Gonzalez, Vanessa ^{[4
,5
,6
]}

Koterba, Natalka ^{[4
,5
,6
]}

Levine, Bruce L. ^{[3
,4
,5
,6
]}

Maude, Shannon L. ^{[1
,2
]}

Meyer, Nuala J. ^{[9
]}

Moore, Jason H. ^{[3
]}

Paessler, Michele ^{[6
]}

Porter, David L. ^{[5
,10
]}

Bush, Jenny L. ^{[11
]}

Siegel, Don L. ^{[4
,5
,6
]}

Davis, Megan M. ^{[4
]}

Zhang, Donglan ^{[11
]}

June, Carl H. ^{[4
,5
,6
]}

Grupp, Stephan A. ^{[1
,2
,5
]}

Melenhorst, J. Joseph ^{[4
,5
,6
]}

Lacey, Simon F. ^{[4
,5
,6
]}

Weiss, Scott L. ^{[11
,12
,13
,14
]}

Teachey, David T. ^{[1
,2
,5
]}

机构：

[1] Childrens Hosp Philadelphia, Div Hematol & Oncol, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] Univ Penn, Ctr Cellular Immunotherapies, Perelman Sch Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA

[8] Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA

[9] Univ Penn, Perelman Sch Med, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA

[10] Univ Penn, Div Hematol Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA

[11] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Div Crit Care Med, Philadelphia, PA 19104 USA

[12] Univ Penn, Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care, Perelman Sch Med, Philadelphia, PA 19104 USA

[13] Childrens Hosp Philadelphia, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA

[14] Childrens Hosp Philadelphia, Pediat Sepsis Program, Philadelphia, PA 19104 USA

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 20期

基金：

美国国家卫生研究院;

关键词：

ENDOTHELIAL ACTIVATION; T-CELLS; NEUROTOXICITY; MANAGEMENT; MECHANISMS; PROFILE; IL-6;

D O I：

10.1182/bloodadvances.2020002592

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Chimeric antigen receptor (CAR) T-cells directed against CD19 have drastically altered outcomes for children with relapsed and refractory acute lymphoblastic leukemia (r/r ALL). Pediatric patients with r/r ALL treated with CAR-T are at increased risk of both cytokine release syndrome (CRS) and sepsis. We sought to investigate the biologic differences between CRS and sepsis and to develop predictive models which could accurately differentiate CRS from sepsis at the time of critical illness. We identified 23 different cytokines that were significantly different between patients with sepsis and CRS. Using elastic net prediction modeling and tree classification, we identified cytokines that were able to classify subjects as having CRS or sepsis accurately. A markedly elevated interferon g (IFN gamma) or a mildly elevated IFN gamma in combination with a low IL1 beta were associated with CRS. A normal to mildly elevated IFN gamma in combination with an elevated IL1 beta was associated with sepsis. This combination of IFN gamma and IL1 beta was able to categorize subjects as having CRS or sepsis with 97% accuracy. As CAR-T therapies become more common, these data provide important novel information to better manage potential associated toxicities.

引用

页码：5174 / 5183

页数：10

共 36 条

[31] Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function [J].

Singh, Nathan ;

Hofmann, Ted J. ;

Gershenson, Zachary ;

Levine, Bruce L. ;

Grupp, Stephan A. ;

Teachey, David T. ;

Barrett, David M. .

CYTOTHERAPY, 2017, 19 (07) :867-880

[32] Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia [J].

Teachey, David T. ;

Lacey, Simon F. ;

Shaw, Pamela A. ;

Melenhorst, J. Joseph ;

Maude, Shannon L. ;

Frey, Noelle ;

Pequignot, Edward ;

Gonzalez, Vanessa E. ;

Chen, Fang ;

Finklestein, Jeffrey ;

Barrett, David M. ;

Weiss, Scott L. ;

Fitzgerald, Julie C. ;

Berg, Robert A. ;

Aplenc, Richard ;

Callahan, Colleen ;

Rheingold, Susan R. ;

Zheng, Zhaohui ;

Rose-John, Stefan ;

White, Jason C. ;

Nazimuddin, Farzana ;

Wertheim, Gerald ;

Levine, Bruce L. ;

June, Carl H. ;

Porter, David L. ;

Grupp, Stephan A. .

CANCER DISCOVERY, 2016, 6 (06) :664-679

[33]

Whitney J, 2020, CRIT CARE MED, V48

[34] Systemic Endothelial Activation Is Associated With Early Acute Respiratory Distress Syndrome in Children With Extrapulmonary Sepsis* [J].

Whitney, Jane E. ;

Zhang, Binqing ;

Koterba, Natalka ;

Chen, Fang ;

Bush, Jenny ;

Graham, Kathryn ;

Lacey, Simon F. ;

Melenhorst, Jan Joseph ;

Teachey, David T. ;

Mensinger, Janell L. ;

Yehya, Nadir ;

Weiss, Scott L. .

CRITICAL CARE MEDICINE, 2020, 48 (03) :344-352

[35] Dynamic Analysis of Cytokine Profile for Cytokine Release Syndrome in Multiple Myeloma Patients after CAR-T Cell Therapy [J].

Yang, Shuangshuang ;

Chen, Lijuan ;

Xu, Jie ;

Fan, Frank Xiao-Hu ;

Yan, Sun ;

Wu, Wen ;

Wang, Yan ;

Wang, Jin ;

Jin, Shiwei ;

Zhou, Yuebo ;

Liu, Yuanfang ;

Zhuang, Yan ;

Zhang, Wu ;

Li, Jun-Min ;

Hou, Jian ;

Li, Jian-Yong ;

Chen, Zhu ;

Mi, Jian-Qing ;

Chen, Sai-Juan .

BLOOD, 2019, 134

[36] Regularization and variable selection via the elastic net [J].

Zou, H ;

Hastie, T .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 2005, 67 :301-320

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