Outcomes of Critically Ill Children With Acute Lymphoblastic Leukemia and Cytokine Release Syndrome Due to Chimeric Antigen Receptor T Cell Therapy: US, Multicenter PICU, Cohort Database Study

Logan, Grace; Miller, Kristen; Kohler, M. Eric; Loi, Michele; Maddux, Aline B

doi:10.1097/pcc.0000000000003079

Cited by 2 publications

(4 citation statements)

References 23 publications

(36 reference statements)

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“…As novel oncologic therapies are introduced, more organ dysfunction related to medication side effects can be seen. For example, engineered chimeric antigen receptor T cells come with toxicity such as cytokine release syndrome that often requires PICU care (8)(9)(10)(11). Additionally, as new therapies are introduced, institutions may implement policies that require the involvement of critical care because of the high risk of serious side effects.…”

Section: Discussionmentioning

confidence: 99%

Critical Care Utilization in Children With Cancer: U.S. Pediatric Health Information System Database Cohort 2012–2021

Rogerson,

Rowan

2023

Pediatric Critical Care Medicine

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Objectives: To determine changes in pediatric oncology hospitalizations requiring intensive care over the period 2012–2021. Design: Retrospective study of hospital admission. Setting: Registry data from 36 children’s hospitals in the U.S. Pediatric Health Information Systems database. Patients: Children 18 years or younger admitted to any of 36 hospitals with an oncology diagnosis. Interventions: None. Measurements and Main Results: There were a total of 55,827 unique patients accounted for 281,221 pediatric oncology hospitalizations over the 10-year period, and 16.6% of hospitalizations included admission to the PICU. Hospitalizations and PICU admissions steadily increased over this decade. Between 2012 and 2016, 15.1% of oncology hospitalizations were admitted to the PICU compared with 18.0% from 2017 to 2021 (difference 2.9% [95% CI, 2.6–3.2%] p ≤ 0.0001). Support with invasive mechanical ventilation also increased over time with 3.7% during 2012–2016 compared with 4.1% from 2017 to 2021 (difference 0.4% [95% CI, 0.2–0.5%] p ≤ 0.0001). Similar results were seen with cardiorespiratory life support using extracorporeal membrane oxygenation (difference 0.05% [95% CI, 0.02–0.07%] p = 0.0002), multiple vasoactive agent use (difference 0.3% [95% CI, 0.2–0.4%] p < 0.0001), central line placement (difference 5.3% [95% CI, 5.1–5.6%], p < 0.001), and arterial line placement (difference 0.4% [95% CI, 0.3–0.4%], p < 0.001). Year-on-year case fatality rate was unchanged over time (1.3%), but admission to the PICU during the second 5 years, compared with the first 5 years, was associated with lower odds of mortality (difference 0.7% [95% CI, 0.3–1.1%]) (odds ratio 0.82 [95% CI, 0.75–0.90%] p < 0.001). Conclusions: The percentage of pediatric oncology hospitalizations resulting in PICU admission has increased over the past 10 years. Despite the increasing use of PICU admission and markers of acuity, and on comparing 2017–2021 with 2012–2016, there are lower odds of mortality.

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Section: Discussionmentioning

confidence: 99%

Critical Care Utilization in Children With Cancer: U.S. Pediatric Health Information System Database Cohort 2012–2021

Rogerson,

Rowan

2023

Pediatric Critical Care Medicine

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“…In our series, two patients died as a consequence of fulminant CRS5-carHLH. CAR T-cell-associated severe carHLH is a rare toxicity related to CAR T-cell therapy which occurs in 1-14% of patients, according to different series ( 37 , 43 ). Its true incidence is unknown due to clinical overlap with high-grade CRS and the high variability in diagnostic criteria used over the last years.…”

Section: Discussionmentioning

confidence: 99%

“…Etoposide, anakinra, cyclophosphamide and extracorporeal cytokine adsorption have been reported with success in few cases ( 44 , 45 ), while other treatments such as ruxolitinib have been recently described. Whereas patients with CRS usually respond to initial therapy, carHLH is associated with high mortality ( 43 ). Suspicion of carHLH should be raised when early occurrence (<5 days after infusion) of ferritin peak (>10,000 ng/mL) or early organ dysfunction and hemophagocytosis in BM ( 43 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

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Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study

Caballero-Bellón,

Alonso-Saladrigues,

Bobillo-Perez

et al. 2023

Front. Immunol.

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IntroductionChimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients.MethodsProspective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality.ResultsCAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344).DiscussionPICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.

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Outcomes of Critically Ill Children With Acute Lymphoblastic Leukemia and Cytokine Release Syndrome Due to Chimeric Antigen Receptor T Cell Therapy: US, Multicenter PICU, Cohort Database Study

Cited by 2 publications

References 23 publications

Critical Care Utilization in Children With Cancer: U.S. Pediatric Health Information System Database Cohort 2012–2021

Critical Care Utilization in Children With Cancer: U.S. Pediatric Health Information System Database Cohort 2012–2021

Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study

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