ArticleCancer discovery2016
Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03994705 (Phase I Safety Study of Descartes-11 in Patients With Relapsed/Refractory Multiple Myeloma), which is not on this map. Cited by 695 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
695citing papers in PubMed, 4 pooled it
44.8field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I Safety Study of Descartes-11 in Patients With Relapsed/Refractory Multiple Myeloma
Who cites it
695 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,063 citations in OpenAlex.
- Association of Ferritin Levels With Cytokine Release Syndrome in CAR T-Cell Therapy: A Systematic Review and Meta-Analysis.Cancer medicine · 2026Pooled it
- Current progress and emerging trends of car-based immunotherapy for hepatocellular carcinoma: a data-driven atlas from multidatabase integration.Frontiers in immunology · 2026Pooled it
- Serum ferritin as a prognostic biomarker in CAR-T therapy for multiple myeloma: A meta-analysis.Biomolecules & biomedicine · 2025Pooled it
- A meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy.Journal of thrombosis and haemostasis : JTH · 2024Pooled it
- BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.Nature medicine · 2026Trial
- Single-cell dynamics of breakthrough toxicities after anakinra prophylaxis for axicabtagene ciloleucel in lymphoma.Blood advances · 2025Trial
- Intelligent immunotherapy: AI-driven optimization of CAR-T therapy in hematologic malignancies.iScience · 2026Review
- Clinical characteristics, treatment and prognosis of nivolumab induced cytokine release syndrome.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- Refining therapeutic targeting of interleukin-6 by signalling mode selectivity.Nature reviews. Drug discovery · 2026Review
- Cytokine release syndrome in adults with acute leukemia after allo-HCT with posttransplant cyclophosphamide prophylaxis.International journal of hematology · 2026Article
- CRS and ICANS: Early detection and personalized management.Blood research · 2026Review
- Predictive Models for Toxicities after CAR T-cell Therapy: Challenges and Opportunities.Blood cancer discovery · 2026Review
- A bispecific CD3×CD19 antibody for systemic lupus erythematosus: a phase 1 trial.Nature medicine · 2026Article
- Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026Review
- Extracting adverse event nature, severity, timelines and resulting interventions from clinical notes of patients receiving CAR-T cell therapy using large language models.PLOS digital health · 2026Article
- Review
- Chimeric antigen receptor T cell therapy cardiotoxicity: a narrative review.Cardio-oncology (London, England) · 2026Review
- Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.Nature medicine · 2026Article
- A single-center retrospective study of short-term efficacy and safety of blinatumomab in the treatment of high-risk acute lymphoblastic leukemia.BMC cancer · 2026Article
- The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.Molecular therapy. Oncology · 2026Review
635 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 4 institutions in 2 countries.
David T TeacheyDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Abramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. teacheyd@email.chop.edu.
Simon F LaceyAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Pamela A ShawDepartment of Biostatistics and Epidemiology, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
J Joseph MelenhorstAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Shannon L MaudeDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Abramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Noelle FreyAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Division of Hematology-Oncology, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Edward PequignotAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Vanessa E GonzalezAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Fang ChenAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Jeffrey FinklesteinAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
David M BarrettDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Abramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Scott L WeissDepartment of Anesthesia and Critical Care Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Julie C FitzgeraldDepartment of Anesthesia and Critical Care Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Robert A BergDepartment of Anesthesia and Critical Care Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Richard AplencDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Abramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Colleen CallahanDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Susan R RheingoldDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Abramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Zhaohui ZhengAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Stefan Rose-JohnInstitute of Biochemistry, CAU Kiel, Germany.
Jason C WhiteFort Belvoir Community Hospital, Fort Belvoir, Virginia.
Farzana NazimuddinAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Gerald WertheimAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Bruce L LevineAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Carl H JuneAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Center for Cellular Immunotherapies, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
David L PorterAbramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Division of Hematology-Oncology, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Stephan A GruppDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Abramson Cancer Center, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
University of Pennsylvania · USChildren's Hospital of Philadelphia · USAlexander T. Augusta Military Medical Center · USChristian-Albrechts-Universität zu Kiel · DE
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3MImproving risk allocation and developing novel therapies for children with T-ALL and T-LLR01CA193776 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Terzah M Horton, ADAM B OLSHEN · 2015 to 2026
$6.2MCD19 Directed CAR TherapyR01CA165206 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H., PORTER, DAVID L · 2012 to 2016
$2.2MUSE OF mTOR INHIBITORS IN B CELL LEUKEMIAR01CA102646 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI GRUPP, STEPHAN A. · 2005 to 2009
$1.6MDeterminants of Relapse Risk After BMT for ALLR01CA116660 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI GRUPP, STEPHAN A. · 2007 to 2011
$1.5MMitochondrial Dysfunction in Pediatric SepsisK23GM110496 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI WEISS, SCOTT L · 2015 to 2018
$723kNCI NIH HHS P30 CA016520NCI NIH HHS R01 CA102646NCI NIH HHS R01 CA116660NCI NIH HHS R01 CA165206NCI NIH HHS R01 CA193776NIGMS NIH HHS K23 GM110496
Abstract
unlabelledChimeric antigen receptor (CAR)-modified T cells with anti-CD19 specificity are a highly effective novel immune therapy for relapsed/refractory acute lymphoblastic leukemia. Cytokine release syndrome (CRS) is the most significant and life-threatening toxicity. To improve understanding of CRS, we measured cytokines and clinical biomarkers in 51 CTL019-treated patients. Peak levels of 24 cytokines, including IFNγ, IL6, sgp130, and sIL6R, in the first month after infusion were highly associated with severe CRS. Using regression modeling, we could accurately predict which patients would develop severe CRS with a signature composed of three cytokines. Results were validated in an independent cohort. Changes in serum biochemical markers, including C-reactive protein and ferritin, were associated with CRS but failed to predict development of severe CRS. These comprehensive profiling data provide novel insights into CRS biology and, importantly, represent the first data that can accurately predict which patients have a high probability of becoming critically ill. SIGNIFICANCE: CRS is the most common severe toxicity seen after CAR T-cell treatment. We developed models that can accurately predict which patients are likely to develop severe CRS before they become critically ill, which improves understanding of CRS biology and may guide future cytokine-directed therapy. Cancer Discov; 6(6); 664-79. ©2016 AACR.See related commentary by Rouce and Heslop, p. 579This article is highlighted in the In This Issue feature, p. 561.
Indexed as
BiomarkersAdolescentAdultAgedAntibodies, Monoclonal, HumanizedAntigens, CD19Cell- and Tissue-Based TherapyChildChild, PreschoolCytokinesFemaleHumansImmunotherapyMaleMiddle AgedPhenotypeAntibodies, Monoclonal, HumanizedAntigens, CD19BiomarkersCytokinesReceptors, Antigen, T-Celltocilizumab
Identifiers
What OpenQuestion holds
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Registered trials
NCT03994705ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.