Hemophagocytic lymphohistiocytosis-like toxicity following chimeric antigen receptor (CAR)-T cell therapy (carHLH) is a rare and fulminant complication. Currently, there are neither well-established diagnostic criteria nor optimal treatment option for carHLH. Given the similarities of hyperinflammatory process and cytokine profiles between cytokine release syndrome (CRS) and carHLH, tocilizumab and corticosteroids are the suggested front-line treatment options for both conditions. However, when carHLH is refractory to front-line treatment, alternative or adjunctive agents should be introduced to ameliorate ongoing hyperinflammation. Anakinra, a recombinant interleukin (IL)-1 receptor antagonist, has shown promising results in the management of carHLH. Although prospective trials are limited, the use of anakinra for severe CRS and carHLH has been increasing. In this case report, we present two cases of carHLH to discuss its characteristic clinical features, diagnostic criteria, and treatment option. In addition, we also highlight the clinical efficacy of anakinra for managing carHLH which was refractory to tocilizumab and dexamethasone.

Background Streptococci are the dominant species in the human oral cavity and upper respiratory tract. Oral mucositis affects 30–40% of the patients receiving chemotherapy and 80% undergoing HSCT. During episode of oral mucositis, patients are at a risk for invasive infections caused by opportunistic pathogens in the oral cavity. The purpose of this study was to investigate the clinical characteristics of S. mitis/oralis invasive infection, and find patients at high risk for with S. mitis/oralis infection in order to prevention of S. mitis/oralis bacteremia. Methods Patients receiving chemotherapy or stem cell transplant for malignancies and primary immunodeficiencies at the pediatric bone marrow transplant center of Seoul St. Mary's hospital admitted during January 2017 to December 2020 for blood stream infections were included in this study. Chart review of the patients were done retrospectively. Results During the four year study period, there were 4,647 admissions, and 2,358 (50.7%) experienced at least 1 episode of fever. Overall, the incidence of bacteremia was 10.9% of all febrile children. The most common pathogen causing bacteremia was S. mitis/oralis (24%), followed by E. coli (14.3%), Klebsiella spp. (10.5%), and S. epidermidis (7.4%). Candida sepsis occurred in 3.5% of the children. By year, the proportion of bacteremia caused by S. mitis/oralis was 19% in 2017, 21% in 2018, 41% in 2019, and 25% in 2020. 51% of S. mitis/oralis bacteremia occurred 8-14 days after day 0 of chemotherapy. A multivariate analyses on risk factors for S. mitis/oralis bacteremia was the underlying disease AML (OR, 4.6; 95% CI, 2.4-8.7; P< 0.001), and the use of cytarabine (OR, 4.5; 95% CI, 2.4-8.5; P< 0.001). Compared to ALL, AML has a HR 3.7 (95% CI 1.9-7.2) of bacteremia with S. mitis/oralis. Prolonged duration of fever ( >7 days) was observed in 13.4% of the patients, and a fever duration >14 days was observed in 2 patients. Complications such as septic shock, n=4 (6.0%), ARDS, n=1 (1.5%), infective endocarditis, n=2 (3.0%) were observed. Conclusion S. mitis/oralis sepsis causes significant morbidity in patients undergoing treatment for malignancies. Patients with AML are at the highest risk, especially after induction or consolidation chemotherapy including cytarabine. Disclosures All Authors: No reported disclosures.