{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T17:35:40Z","timestamp":1791740140793,"version":"4.3.4"},"reference-count":93,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T00:00:00Z","timestamp":1636156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast these features in advance. However, a broad range of cytokines are involved in the dynamics of CRS. Treatment approaches include both broad spectrum of immunosuppressant, such as corticosteroids, as well as more specific inhibition of cytokine release. In the present manuscript we will try to review an update regarding pathophysiology, etiology, diagnostics, and therapeutic options for this serious complication.<\/jats:p>","DOI":"10.3390\/jcm10215190","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:41:14Z","timestamp":1636317674000},"page":"5190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences"],"prefix":"10.3390","volume":"10","author":[{"given":"Tor Henrik Anderson","family":"Tvedt","sequence":"first","affiliation":[{"name":"Department of Hematology, Oslo University Hospital, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Khoi","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ystein","family":"Bruserud","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Clinic for Medicine, Haukeland University Hospital, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kon","family":"Reikvam","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Clinic for Medicine, Haukeland University Hospital, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1056\/NEJM198905253202117","article-title":"Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-gamma [corrected]","volume":"320","author":"Chatenoud","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/ITT.S202015","article-title":"Cytokine Release Syndrome: Current Perspectives","volume":"8","author":"Murthy","year":"2019","journal-title":"Immunotargets Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1016\/j.bbmt.2018.12.756","article-title":"Cytokine Release Syndrome with Chimeric Antigen Receptor T Cell Therapy","volume":"25","author":"Frey","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/16078454.2018.1549802","article-title":"Efficacy and safety of bispecific T-cell engager (BiTE) antibody blinatumomab for the treatment of relapsed\/refractory acute lymphoblastic leukemia and non-Hodgkin\u2019s lymphoma: A systemic review and meta-analysis","volume":"24","author":"Yu","year":"2019","journal-title":"Hematology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100707","DOI":"10.1016\/j.blre.2020.100707","article-title":"Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes","volume":"45","author":"England","year":"2021","journal-title":"Blood Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1182\/blood-2017-06-793141","article-title":"Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy","volume":"130","author":"Hay","year":"2017","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in CAR T cell therapy","volume":"17","author":"Rafiq","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa063842","article-title":"Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412","volume":"355","author":"Suntharalingam","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14397","DOI":"10.1038\/s41598-021-93842-0","article-title":"Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning","volume":"11","author":"Haber","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1002\/eji.202149181","article-title":"Immunological analysis of the murine anti-CD3-induced cytokine release syndrome model and therapeutic efficacy of anti-cytokine antibodies","volume":"51","author":"Nouveau","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Webster, A.C., Ruster, L.P., McGee, R., Matheson, S.L., Higgins, G.Y., Willis, N.S., Chapman, J.R., and Craig, J.C. (2010). Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst. Rev., CD003897.","DOI":"10.1002\/14651858.CD003897.pub3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1097\/01.tp.0000168153.50774.30","article-title":"Induction therapy for pediatric and adult heart transplantation: Comparison between OKT3 and daclizumab","volume":"80","author":"Chin","year":"2005","journal-title":"Transplantation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1517\/14712598.2011.592824","article-title":"Alemtuzumab in allogeneic hematopoetic stem cell transplantation","volume":"11","author":"Poire","year":"2011","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1053\/j.seminhematol.2016.01.004","article-title":"Haploidentical stem cell transplantation: Anti-thymocyte globulin-based experience","volume":"53","author":"Chang","year":"2016","journal-title":"Semin Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/anr3.12092","article-title":"Severe anti-thymocyte globulin-induced cytokine release syndrome in a renal transplant patient","volume":"9","author":"Huh","year":"2021","journal-title":"Anaesth. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s12185-019-02660-8","article-title":"HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide","volume":"110","author":"Sugita","year":"2019","journal-title":"Int. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1053\/j.seminhematol.2018.08.003","article-title":"Who is the best donor for haploidentical stem cell transplantation?","volume":"56","author":"Kongtim","year":"2019","journal-title":"Semin Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/ajh.23995","article-title":"An overview of conditioning regimens for haploidentical stem cell transplantation with post-transplantation cyclophosphamide","volume":"90","author":"Lombardi","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e157","DOI":"10.1016\/S2352-3026(19)30256-X","article-title":"Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: Updated consensus recommendations of the European Society for Blood and Marrow Transplantation","volume":"7","author":"Penack","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41409-021-01403-w","article-title":"Cytokine release syndrome after haploidentical hematopoietic cell transplantation: An international multicenter analysis","volume":"56","author":"Abboud","year":"2021","journal-title":"Bone Marrow Transpl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1016\/j.bbmt.2016.06.010","article-title":"Severe Cytokine-Release Syndrome after T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated with Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated","volume":"22","author":"Abboud","year":"2016","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e387","DOI":"10.1016\/j.bbmt.2019.09.013","article-title":"Dual T Cell Depletion with Anti-Thymocyte Globulin and Post-Transplant Cyclophosphamide Results in Low Rates of Cytokine Release Syndrome in Peripheral Blood Haplo-Hematopoietic Stem Cell Transplantation","volume":"25","author":"Salas","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1016\/j.bbmt.2020.01.004","article-title":"Prevention and Treatment of Acute Graft-versus-Host Disease in Children, Adolescents, and Young Adults","volume":"26","author":"Gatza","year":"2020","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1158\/2159-8290.CD-16-0040","article-title":"Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia","volume":"6","author":"Teachey","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","article-title":"CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade","volume":"24","author":"Giavridis","year":"2018","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.blre.2018.11.002","article-title":"Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management","volume":"34","author":"Brudno","year":"2019","journal-title":"Blood Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","article-title":"Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells","volume":"24","author":"Norelli","year":"2018","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1600-0609.1993.tb01596.x","article-title":"IFN-gamma and TNF-alpha secretion by CD4+ and CD8+ TCR alpha beta + T-cell clones derived early after allogeneic bone marrow transplantation","volume":"51","author":"Bruserud","year":"1993","journal-title":"Eur. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1365-3083.1993.tb01695.x","article-title":"Secretion of IL-2, IL-3, IL-4, IL-6 and GM-CSF by CD4+ and CD8+ TCR alpha beta+ T-cell clones derived early after allogeneic bone marrow transplantation","volume":"38","author":"Bruserud","year":"1993","journal-title":"Scand. J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1600-0609.1995.tb01776.x","article-title":"Secretion of leukaemia inhibitory factor after allogeneic bone marrow transplantation: A study of CD4+ and CD8+ TCR alpha beta+ T-cell clones derived from four leukaemia patients","volume":"54","author":"Bruserud","year":"1995","journal-title":"Eur. J. Haematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jim.2018.06.003","article-title":"Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood","volume":"461","author":"Rundgren","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5430","DOI":"10.1074\/jbc.AC119.007558","article-title":"Granulocyte-macrophage colony-stimulating factor inactivation in CAR T-cells prevents monocyte-dependent release of key cytokine release syndrome mediators","volume":"294","author":"Sachdeva","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rundgren, I.M., Ryningen, A., Anderson Tvedt, T.H., Bruserud, O., and Ersvaer, E. (2020). Immunomodulatory Drugs Alter the Metabolism and the Extracellular Release of Soluble Mediators by Normal Monocytes. Molecules, 25.","DOI":"10.3390\/molecules25020367"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Root-Bernstein, R. (2021). Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI\/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042108"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107087","DOI":"10.1016\/j.intimp.2020.107087","article-title":"Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets","volume":"89","author":"Kumar","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cytogfr.2020.09.002","article-title":"Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?","volume":"58","author":"Brandao","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"583513","DOI":"10.3389\/fimmu.2020.583513","article-title":"Roles of Interactions Between Toll-Like Receptors and Their Endogenous Ligands in the Pathogenesis of Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still\u2019s Disease","volume":"11","author":"Jung","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1093\/ndt\/gft446","article-title":"Toll-like receptors: Sensing and reacting to diabetic injury in the kidney","volume":"29","author":"Lin","year":"2014","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1517\/14728222.2010.525021","article-title":"Therapeutic targeting of NF-kappaB in myelodysplastic syndromes and acute myeloid leukaemia\u2014The biological heterogeneity","volume":"14","author":"Bruserud","year":"2010","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3389\/fimmu.2016.00507","article-title":"Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation","volume":"7","author":"Ogonek","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rundgren, I.M., Ersvaer, E., Ahmed, A.B., Ryningen, A., and Bruserud, O. (2019). Circulating monocyte subsets in multiple myeloma patients receiving autologous stem cell transplantation\u2014A study of the preconditioning status and the course until posttransplant reconstitution for a consecutive group of patients. BMC Immunol., 20.","DOI":"10.1186\/s12865-019-0323-y"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"224ra225","DOI":"10.1126\/scitranslmed.3008226","article-title":"Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia","volume":"6","author":"Davila","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/ana.25502","article-title":"Glial injury in neurotoxicity after pediatric CD19-directed chimeric antigen receptor T cell therapy","volume":"86","author":"Gust","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"177ra138","DOI":"10.1126\/scitranslmed.3005930","article-title":"CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia","volume":"5","author":"Brentjens","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1182\/blood-2011-10-384388","article-title":"B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells","volume":"119","author":"Kochenderfer","year":"2012","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1182\/blood-2017-08-802413","article-title":"Cytokine release syndrome associated with chimeric-antigen receptor T-cell therapy: Clinicopathological insights","volume":"130","author":"Obstfeld","year":"2017","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bruserud, O., Aarstad, H.H., and Tvedt, T.H.A. (2020). Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer-What Can We Learn from the Hematological Experience?. Cancers, 12.","DOI":"10.3390\/cancers12071966"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.hemonc.2020.09.004","article-title":"C-reactive protein and ferritin levels and length of intensive care unit stay in patients with B-cell lymphomas treated with axicabtagene ciloleucel","volume":"14","author":"Melody","year":"2021","journal-title":"Hematol. Oncol. Stem. Cell. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1182\/blood-2018-12-893396","article-title":"Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells","volume":"133","author":"Karschnia","year":"2019","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sandnes, M., Ulvik, R.J., Vorland, M., and Reikvam, H. (2021). Hyperferritinemia-A Clinical Overview. J. Clin. Med., 10.","DOI":"10.3390\/jcm10092008"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/mt.2010.31","article-title":"Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: Case report of an unforeseen adverse event in a phase I clinical trial","volume":"18","author":"Brentjens","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_52","first-page":"159","article-title":"Effect of anti-CD19 chimeric antigen receptor T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia and its prognosis","volume":"26","author":"Li","year":"2021","journal-title":"J. BUON"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1182\/bloodadvances.2021004575","article-title":"CRP and ferritin in addition to the EASIX score predict CAR-T-related toxicity","volume":"5","author":"Greenbaum","year":"2021","journal-title":"Blood Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1684\/ecn.2012.0322","article-title":"The angioregulatory cytokine network in human acute myeloid leukemia\u2014From leukemogenesis via remission induction to stem cell transplantation","volume":"23","author":"Reikvam","year":"2012","journal-title":"Eur. Cytokine Netw."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/1744666X.2019.1629904","article-title":"Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome","volume":"15","author":"Kotch","year":"2019","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-3-540-73259-4_7","article-title":"Humanized antihuman IL-6 receptor antibody, tocilizumab","volume":"10","author":"Nishimoto","year":"2008","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2217\/imt-2016-0020","article-title":"Immunotherapeutic implications of IL-6 blockade for cytokine storm","volume":"8","author":"Tanaka","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(03)15326-3","article-title":"Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock","volume":"363","author":"Pathan","year":"2004","journal-title":"Lancet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s11897-021-00505-2","article-title":"Biomarkers of Cardiac Stress and Cytokine Release Syndrome in COVID-19: A Review","volume":"18","author":"Gordon","year":"2021","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40364-018-0116-0","article-title":"Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy","volume":"6","author":"Wang","year":"2018","journal-title":"Biomark Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"943430","DOI":"10.1155\/2015\/943430","article-title":"Metabolic Serum Profiles for Patients Receiving Allogeneic Stem Cell Transplantation: The Pretransplant Profile Differs for Patients with and without Posttransplant Capillary Leak Syndrome","volume":"2015","author":"Reikvam","year":"2015","journal-title":"Dis. Markers"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.molimm.2017.05.013","article-title":"Complement in clinical medicine: Clinical trials, case reports and therapy monitoring","volume":"89","author":"Ricklin","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1056\/NEJMra0904569","article-title":"The tumor lysis syndrome","volume":"364","author":"Howard","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1161\/ATVBAHA.108.180497","article-title":"Macrophage diversity and polarization in atherosclerosis: A question of balance","volume":"29","author":"Mantovani","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1086\/517807","article-title":"Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever","volume":"177","author":"Bethell","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3109\/10428199609054849","article-title":"Serum levels of adhesion molecules and cytokines in patients with acute leukaemia","volume":"23","author":"Bruserud","year":"1996","journal-title":"Leuk Lymphoma"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3389\/fmed.2018.00147","article-title":"Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis","volume":"5","author":"Mosevoll","year":"2018","journal-title":"Front. Med. (Lausanne)"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/j.1365-2141.1995.tb05309.x","article-title":"Serum concentrations of E-selectin, P-selectin, ICAM-1 and interleukin 6 in acute leukaemia patients with chemotherapy-induced leucopenia and bacterial infections","volume":"91","author":"Bruserud","year":"1995","journal-title":"Br. J. Haematol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Aarstad, H.H., Moe, S.E.E., Bruserud, O., Lybak, S., Aarstad, H.J., and Tvedt, T.H.A. (2020). The Acute Phase Reaction and Its Prognostic Impact in Patients with Head and Neck Squamous Cell Carcinoma: Single Biomarkers Including C-Reactive Protein Versus Biomarker Profiles. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100418"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Aarstad, H.H., Guethbrandsdottir, G., Hjelle, K.M., Bostad, L., Bruserud, O., Tvedt, T.H.A., and Beisland, C. (2020). The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile. Cancers, 12.","DOI":"10.3390\/cancers12071961"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41569-020-0348-1","article-title":"Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia","volume":"17","author":"Herrmann","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e2020009","DOI":"10.4084\/mjhid.2020.009","article-title":"Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment","volume":"12","author":"Hansen","year":"2020","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/bjh.15274","article-title":"How i treat primary haemophagocytic lymphohistiocytosis","volume":"182","author":"Marsh","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1586\/ehm.11.54","article-title":"The chemokine system in allogeneic stem-cell transplantation: A possible therapeutic target?","volume":"4","author":"Melve","year":"2011","journal-title":"Expert. Rev. Hematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-981-13-3681-2_2","article-title":"The Immune System and Its Dysregulation with Aging","volume":"91","author":"Muller","year":"2019","journal-title":"Subcell Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Tvedt, T.H., Lie, S.A., Reikvam, H., Rye, K.P., Lindas, R., Gedde-Dahl, T., Ahmed, A.B., and Bruserud, O. (2016). Pretransplant Levels of CRP and Interleukin-6 Family Cytokines; Effects on Outcome after Allogeneic Stem Cell Transplantation. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111823"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/hon.2772","article-title":"Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide","volume":"38","author":"Solan","year":"2020","journal-title":"Hematol. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Godel","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/j.1365-2141.2005.05509.x","article-title":"Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: Results of the UK Medical Research Council ALL97 randomized trial","volume":"129","author":"Mitchell","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/ATVBAHA.119.313536","article-title":"Proinflammatory Mediators, IL (Interleukin)-1beta, TNF (Tumor Necrosis Factor) alpha, and Thrombin Directly Induce Capillary Tube Regression","volume":"40","author":"Koller","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s12975-018-0614-2","article-title":"Interleukin 6-Mediated Endothelial Barrier Disturbances Can Be Attenuated by Blockade of the IL6 Receptor Expressed in Brain Microvascular Endothelial Cells","volume":"9","author":"Wagner","year":"2018","journal-title":"Transl. Stroke Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ridiandries, A., Tan, J.T., and Bursill, C.A. (2016). The Role of CC-Chemokines in the Regulation of Angiogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111856"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"830","DOI":"10.18632\/oncotarget.971","article-title":"Pharmacological targeting of the PI3K\/mTOR pathway alters the release of angioregulatory mediators both from primary human acute myeloid leukemia cells and their neighboring stromal cells","volume":"4","author":"Reikvam","year":"2013","journal-title":"Oncotarget"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1182\/blood-2004-08-2997","article-title":"Macrophage activation syndrome: Characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages","volume":"105","author":"Billiau","year":"2005","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1056\/NEJMoa1609783","article-title":"Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia","volume":"376","author":"Kantarjian","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1002\/art.39295","article-title":"Inhibition of natural killer cell cytotoxicity by interleukin-6: Implications for the pathogenesis of macrophage activation syndrome","volume":"67","author":"Cifaldi","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.3389\/fimmu.2019.02319","article-title":"Interleukin-6 as Biomarker for Acute GvHD and Survival After Allogeneic Transplant With Post-transplant Cyclophosphamide","volume":"10","author":"Greco","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1016\/j.bbmt.2019.07.027","article-title":"Severe Cytokine Release Syndrome after Haploidentical Peripheral Blood Stem Cell Transplantation","volume":"25","author":"Imus","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"930.e1","DOI":"10.1016\/j.jtct.2021.07.007","article-title":"Patient-Reported Symptom and Functioning Status during the First 12 Months after Chimeric Antigen Receptor T Cell Therapy for Hematologic Malignancies","volume":"27","author":"Wang","year":"2021","journal-title":"Transpl. Cell Ther."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/21\/5190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:26:52Z","timestamp":1760167612000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/21\/5190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,6]]},"references-count":93,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["jcm10215190"],"URL":"https:\/\/doi.org\/10.3390\/jcm10215190","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,6]]}}}