Cytokine syndromes associated with hematopoietic cellular therapy

Abstract

The clinical manifestations of excess production of proinflammatory cytokines associated with hematopoietic cell therapy are being increasingly recognized. While these manifestations are all forms of a cytokine release syndrome (CRS), the terminology to date has focused on the clinical scenarios in which they occur (eg, graft vs host disease [GVHD] or engraftment syndrome [ES] following hematopoietic cell transplantation or CRS following immune effector cell therapy). The data regarding cytokine profiles in these conditions are limited by the variable methods of assessment and which cytokines are measured. Overlapping cytokine profiles are seen in these conditions, but distinct differences in the profiles have also been described (eg, for acute GVHD and ES). Targeted interventions have been developed based on these profiles with some (eg, anti-interleukin-6 receptor antibody therapy for CRS after immune effector cell therapy) showing more promise than others. Future strategies include the evaluation of monoclonal antibodies against more recently described cytokines and the increasing use of less specific inhibitors of cytokine production such as the Janus Kinase/Transducer and Activator of Transcription signaling inhibitors.