BACKGROUND: Anti-CD19 CAR T cell therapy has demonstrated high response rates in 
patients with relapsed or refractory (r/r) B cell malignancies but is associated 
with significant toxicity. Cytokine release syndrome (CRS) is the most 
significant complication associated with CAR T cell therapy, and it is critical 
to have a reproducible and easy method to grade CRS after CAR T cell infusions.
DISCUSSION: The Common Terminology Criteria for Adverse Events scale is 
inadequate for grading CRS associated with cellular therapy. Clinical experience 
with the anti-CD19 CAR T cell therapy tisagenlecleucel at the University of 
Pennsylvania (Penn) was used to develop the Penn grading scale for CRS. The Penn 
grading scale depends on easily accessible clinical features; does not rely on 
location of care or quantitation of supportive care; assigns grades to guide CRS 
management; distinguishes between mild, moderate, severe, and life-threatening 
CRS; and applies to both early-onset and delayed-onset CRS associated with T 
cell therapies. Clinical data from 55 pediatric patients with r/r B cell acute 
lymphoblastic leukemia and 42 patients with r/r chronic lymphocytic lymphoma 
treated with tisagenlecleucel were used to demonstrate the current application 
of the Penn grading scale.
CONCLUSION: We show that the Penn grading scale provides reproducible CRS 
grading that can be useful to guide therapy and that can be applied across 
clinical trials and treatment platforms.