Kidney Disease after CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Pediatric Acute Lymphoblastic Leukemia
Background:
Chimeric Antigen Receptor (CAR) T cell therapy has been a transformative treatment for children with acute lymphoblastic leukemia (ALL) whose disease has relapsed or not responded to other therapies. However, CAR T-cell therapy is also associated with toxicities, which may be severe. One common side effect is acute kidney injury, but the spectrum of kidney disease has not previously been well described. In addition, we do not know if CAR T- cell therapy has any long-term effects on the kidney.
Project Goal:
The propose a study to evaluate acute and chronic kidney disease after CAR T cell therapy. Our first aim is to characterize acute kidney injury in the first 30 days after CAR T cell infusion, by assessing its incidence, severity, outcome and risk factors. Our second aim is to compare the changes in kidney function after CAR T cell infusion with the changes in other important laboratory tests that are related to cytokine release syndrome or tumor lysis syndrome. This will help us understand the mechanisms that lead to kidney injury and identify specific times after CAR T cell infusion that clinicians may be able to intervene to prevent or lessen kidney injury. Our third aim is to evaluate whether acute kidney injury in the first 30 days after infusion is associated with chronic kidney disease 3, 6, and 12 months later. This will help us understand what impact CAR T cell therapy may have on long-term kidney function. We will accomplish our aims by assessing a cohort of 160-200 children, who received CAR T cell therapy at Children's Hospital of Philadelphia between 2012 and 2018, either on or off a clinical trial. We will use a data extraction tool that queries the children's electronic medical records and automatically returns all their laboratory results, medications administered, and vital sign information to secure data files. We will also analyze cytokine values that were run as part of previous clinical trials. In order to evaluate long-term renal function, we will test the level of a biomarker called cystatin C on blood samples that were previously collected and stored.
The results of this study will provide important guidance to patients and their families, clinicians and other researchers. The study will help us understand the burden and impact of kidney injury as well as identify key strategies and timepoints for intervention to mitigate kidney disease. In addition, the results will help inform the development of multiple, future projects, including studies that collect and test blood and urine samples upfront to better understand the mechanisms of kidney injury and studies that investigate other, potentially severe toxicities of CAR T cells.
