Infections Presenting 30 Days After Chimeric Antigen Receptor (CAR) Modified T Cells: A Single-Center Experience

Abstract

Background. Targeted therapy using chimeric antigen receptor (CAR) modified T cells is being studied for patients with relapsed acute lymphoblastic leukemia (ALL). Potential infectious complications stemming from CAR T cell infusion therapy (CTI) are unknown. Methods. We reviewed records of adults with relapsed ALL at a tertiary cancer center to determine the infectious complications within 30 days of the first CTI. Demographics, clinical, and microbiological data were evaluated in addition to pathology and radiology reports. Results. Forty-eight ALL patients received CTI therapy after lymphodepleting chemotherapy (cyclophosphamide alone or with fludarabine) between May 2010 and November 2015. The majority were Caucasian (85.4%) with a median age of 46 (range: 22-74) years and a median of 3.4 prior lines of ALL therapy. Eighteen (37.5%) had relapsed disease after allogeneic stem cell transplant. At the time of CTI, 28 (58.3%) were lymphopenic and 19 (39.5%) were neutropenic. Median duration of lymphopenia and neutropenia prior to CTI was 4.5 (range: 0-108) and 15 (range: 0-83) days, respectively. After CTI, all patients had neutropenia (range: 1-77 days) and among these, 37 (77%) developed fever requiring antimicrobial escalation. Twenty-one patients (43.7%) had a documented infection after CTI. Bacterial infections predominated including 6 cases of bacteremia (3 Enterococcus faecium, one each for Escherichia coli, Pseudomonas aeruginosa and Stenotrophomonas maltophilia), 4 cases of Clostridium difficile colitis, 3 cases of polymicrobial intra-abdominal infections; 2 healthcare-associated pneumonias; and 2 complicated urinary tract infections. Respiratory viral infections followed a seasonal pattern with three Rhino/Enterovirus and three Parainfluenza virus type 3 respiratory tract infections identified. There were 4 proven invasive mold infections and one case of S. cerevisiae fungemia, all while receiving micafungin as antifungal prophylaxis. Conclusion. This cohort of patients exhibited a significant risk of invasive bacterial and fungal disease within 30 days after completing chemotherapy and CTI. Our findings may aid in future prophylactic strategies but further studies are needed as we gain experience with these new modalities of treatment.