How I treat cytopenias after CAR T-cell therapy

[Display omitted] Increasing use of chimeric antigen receptor T-cell therapy (CAR-T) has unveiled diverse toxicities warranting specific recognition and management. Cytopenias occurring after CAR-T infusion invariably manifest early (90 days). Variable etiologies of these cytopenias, some of which remain incompletely understood, create clinical conundrums and uncertainties about optimal management strategies. These cytopenias may cause additional sequelae, decreased quality of life, and increased resource use. Early cytopenias are typically attributed to lymphodepletion chemotherapy, however, infections and hyperinflammatory response such as immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome may occur. Early and prolonged cytopenias often correlate with severity of cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome. Bone marrow biopsy in patients with prolonged or late cytopenias is important to evaluate for primary disease and secondary marrow neoplasm in both pediatric and adult patients. Commonly, cytopenias resolve over time and evidence for effective interventions is often anecdotal. Treatment strategies, which are limited and require tailoring based upon likely underlying etiology, include growth factors, thrombopoietin-receptor agonist, stem cell boost, transfusion support, and abrogation of infection risk. Here we provide our approach, including workup and management strategies, for cytopenias after CAR-T. With 6 chimeric antigen receptor (CAR) T-cell products approved by the US Food and Drug Administration and many more showing promise in clinical trials, the need for hematologists to be aware of challenging complications and know how to manage them in routine practice is paramount. Introduced by Associate Editor Helen E. Heslop, this How I Treat series highlights several key complications, reviews current understanding of their etiologies, and provides guidance on therapies through discussion of illustrative cases.