We present the case of a 6 year old boy, with relapsed Acute Lymphoblastic Leukaemia and subsequent matched unrelated bone marrow transplant. His Epstein Barr Virus (EBV) titres were significant 6 months post-transplant with evidence of EBV related lymphoproliferative disease. Following local protocols, Rituximab was used for therapy and within minutes of starting the infusion the patient suffered pyrexia, hypotension and seizures with subsequent multi-organ failure, due to a cytokine storm. Organ damage included fulminant hepatic failure, renal failure meriting dialysis, cardiac failure requiring inotropic support and a significant acute brain injury. There was significant neurological impairment with radiological and electrophysiological evidence of global brain cell damage. As a result of irreversible neurological injury, the focus of treatment was switched from curative to palliative.
Cytokine storm is an immune mediated phenomenon, characterised by an overwhelming release of cytokines. This can produce a sepsis like response and may lead to multi-organ failure. Cytokines are normally produced by leucocytes as a response to an infective or inflammatory process and their main role is to induce leukopoeisis.
Rituximab is an anti-CD20 monoclonal antibody that has been useful in treating EBV related lymphoproliferative disease. Rituximab triggers the rapid release of cytokines that may lead to a cytokine storm with maximum levels within 2 h from the start of the infusion.
Cytokine storms are characterised by overproduction of immune mediators that in turn lead to cellular overactivation, increased endothelial permeability, polymorphonuclear neutrophil adhesion and migration. As there is lack of regulatory intervention, tissue congestion with activated leucocytes ensues which eventually causes parenchymal injury. Although we report multi-organ failure in this case, lungs and gut are the organs that are more commonly affected.
The incidence of cytokine storm in paediatric oncology patients is not known. It has been associated with haemophagocytic lymphohistiocytosis, graft-versus-host disease following haemopoetic stem cell transplant and the use of certain monoclonal antibodies. As in this case, results of the cytokine storm can be catastrophic, despite early recognition.
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