How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis*

Carcillo, Joseph A.; Simon, Dennis; Podd, Bradley S.

doi:10.1097/pcc.0000000000000460

Cited by 38 publications

(24 citation statements)

References 19 publications

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“…Another important distinction between CRS and other forms of refractory shock is related to adjunctive shock therapy. Corticosteroid administration remains in the practice parameters for treatment of refractory pediatric shock (25) and is a mainstay of MAS/HLH therapy (26, 27); however, corticosteroid therapy may inhibit CAR T cell therapy efficacy (10, 12, 13, 28). …”

Section: Discussionmentioning

confidence: 99%

Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia

Fitzgerald

Weiss

Maude

et al. 2017

Critical Care Medicine

400

340

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Objective Initial success with chimeric antigen receptor–modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor–modified T cell therapy. Design Retrospective cohort study. Setting Academic children’s hospital. Patients Thirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor–modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495). Interventions All subjects received chimeric antigen receptor–modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab. Measurements and Main Results Eighteen subjects (46%) developed grade 3–4 cytokine release syndrome, with prolonged fever (median, 6.5 d), hyperferritinemia (median peak ferritin, 60,214 ng/mL), and organ dysfunction. Fourteen (36%) developed cardiovascular dysfunction treated with vasoactive infusions a median of 5 days after T cell therapy. Six (15%) developed acute respiratory failure treated with invasive mechanical ventilation a median of 6 days after T cell therapy; five met criteria for acute respiratory distress syndrome. Encephalopathy, hepatic, and renal dysfunction manifested later than cardiovascular and respiratory dysfunction. Subjects had a median of 15 organ dysfunction days (interquartile range, 8–20). Treatment with tocilizumab in 13 subjects resulted in rapid defervescence (median, 4 hr) and clinical improvement. Conclusions Grade 3–4 cytokine release syndrome occurred in 46% of patients following T cell therapy for relapsed/refractory acute lymphoblastic leukemia. Clinicians should be aware of expanding use of this breakthrough therapy and implications for critical care units in cancer centers.

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Section: Discussionmentioning

confidence: 99%

Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia

Fitzgerald

Weiss

Maude

et al. 2017

Critical Care Medicine

400

340

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“…Serological indicators can objectively indicate changes in the sepsis condition and provide a direct basis for assessing the outcome of the disease after treatment. For example, CRP and PCT are clinically widely used indicators of inflammation[22,23]. They have a high specificity in the diagnosis of the degree of inflammation[24].…”

Section: Discussionmentioning

confidence: 99%

Nested case-control study of multiple serological indexes and Brighton pediatric early warming score in predicting death of children with sepsis

Xie

Xiong³

et al. 2019

WJCC

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BACKGROUND Currently, it is difficult to predict the complications of children at the early stage of sepsis. Brighton pediatric early warning score (PEWS) is a disease risk assessment system that is simple and easy to operate, which has good sensitivity and specificity in disease recognition among children. Because detection indicators vary widely in children, a single indicator is difficult to assess the post-treatment status of children with sepsis. AIM To investigate the relationship between serological markers, Brighton PEWS, and death in children with sepsis after treatment. METHODS A total of 205 children diagnosed with sepsis at our hospital were enrolled. The baseline data, serum scores, and PEWS scores were recorded. In the nested case-control study, children who died during the study period were included in an observation group. According to the matching principle, the children who were not dead in the same cohort were included in a control group. The influencing factors of death in children with sepsis after treatment and the value of each evaluation index in predicting the prognosis of children were analyzed. RESULTS A total of 96 children were enrolled in the study, including 48 each in the observation group and the control group. Multivariate logistic regression analysis indicated that antibacterial treatments within 1 h ( P = 0.017), shock ( P = 0.044), multiple organ dysfunction syndrome (MODS) ( P = 0.027), serum procalcitonin (PCT) ( P = 0.047), serum albumin (ALB) ( P = 0.024), and PEWS ( P = 0.012) were independent risk factors for the death of children with sepsis. The area under the curve of the combination of ALB, PCT, and PEWS to predict the death in children with sepsis was the highest (0.908). CONCLUSION Antibacterial treatments within 1 h, shock, MODS, PCT, ALB, and PEWS are independent risk factors for the death of children with sepsis. The predictive accuracy of the combination of PCT, ALB, and PEWS for the prognosis of children with sepsis is the best.

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“…Several diseases that may present both hyperinflammation and hyperferritinemia have been grouped under this common umbrella named hyperferritinemic syndrome (Table 1 ). These include MAS, a secondary form of HLH, AOSD, cAPS and septic shock [ 32 , 33 ]. Although these conditions are characterized by different pathogenesis and clinical presentation, it is likely that pathogenically elevated levels of ferritin sustain the inflammatory process [ 32 ].…”

Section: Hyperferritinemic Syndromementioning

confidence: 99%

COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy

et al. 2020

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SARS-CoV-2 infection is characterized by a protean clinical picture that can range from asymptomatic patients to life-threatening conditions. Severe COVID-19 patients often display a severe pulmonary involvement and develop neutrophilia, lymphopenia, and strikingly elevated levels of IL-6. There is an over-exuberant cytokine release with hyperferritinemia leading to the idea that COVID-19 is part of the hyperferritinemic syndrome spectrum. Indeed, very high levels of ferritin can occur in other diseases including hemophagocytic lymphohistiocytosis, macrophage activation syndrome, adult-onset Still’s disease, catastrophic antiphospholipid syndrome and septic shock. Numerous studies have demonstrated the immunomodulatory effects of ferritin and its association with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. Iron chelation represents a pillar in the treatment of iron overload. In addition, it was proven to have an anti-viral and anti-fibrotic activity. Herein, we analyse the pathogenic role of ferritin and iron during SARS-CoV-2 infection and propose iron depletion therapy as a novel therapeutic approach in the COVID-19 pandemic.

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How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis*

Cited by 38 publications

References 19 publications

Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia

Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia

Nested case-control study of multiple serological indexes and Brighton pediatric early warming score in predicting death of children with sepsis

COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy

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