Thrombotic microangiopathy following chimeric antigen receptor T-cell therapy

Abstract

INTRODUCTION: Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia and is associated with a variety of conditions and following hematopoietic stem cell transplantation. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel immunotherapeutic approach using genetically modified autologous T cells. CAR-T therapy has been linked with injuries to vascular endothelium, but a direct association between CAR-T and TMA has not been reported. CASE REPORTS: Two cases of TMAs following CAR-T treatment are reported here. In each case, clinical evidence of kidney injury, thrombocytopenia, and hemolytic anemia became apparent 2 - 3 months following CAR-T infusion. We describe the clinical course, management, and outcome of these experiences. DISCUSSION/CONCLUSION: CAR-T cell therapy-associated TMA (CAR-T TMA) appear to be an entity that shares overlapping clinical features with transplant-associated TMA (TA-TMA). Based on our preliminary clinical observations, we discuss the best clinical diagnosis/classification criteria, underlying pathophysiology, and the implication of the apparently self-limiting course. With increasing use of CAR-T cell treatment in hematologic malignancies, systematic studies will be necessary to improve management of CAR-T TMA.