Introduction: Rituximab is a monoclonal antibody used to treat hematological malignancies. The antibody depletes CD20+ B cells via cytotoxic immune mechanisms, such as complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which is mainly induced by natural killer (NK) cells. Rituximab is mostly well-tolerated but has been reported to induce the release of large amounts of cytokines in blood, thus causing systemic inflammatory response. Aim: To study rituximab-induced B cell depletion and cytokine release in blood from healthy volunteers and how this was affected by Fc modified versions of the antibody. Methods and materials: Fresh blood from healthy donors (n=3) was incubated with rituximab and Fc modified versions that influence the antibody’s target functions, namely ADCC and CDC, for 4 hours in a blood loop system. Results were measured using multicolor flow cytometry, except for cytokine release in plasma which was measured by enzyme-linked immunosorbent assay (ELISA). Results: Of all treatments, rituximab wild type (WT) showed superior B cell depletion than Fc mutant rituximab. The C1q knock-out variant (rituximab-P331S) and the variant with improved affinity to Fc receptor CD16 (rituximab-GASDALIE) did not differ in depletion. A cytokine release was not detected with the treatments, however, a cytokine stimulation in NK cells was observed. Rituximab-GASDALIE had the most prominent cytokine stimulation and CD107a (marker of NK cell functional activity) expression on NK cells. Rituximab-WT and rituximab-P331S had a minor and similar cytokine stimulation and CD107a expression between each other. Rituximab-IgG2 had minimal B cell depletion, CD107a expression and cytokine stimulation. Conclusions: Rituximab depleted B cells without inducing measurable cytokine release for healthy individuals. Among the treatments, Fc mutant rituximab seem to induce less B cell depletion. Moreover, rituximab-GASDALIE appear to elicit an enhanced NK cell activation. Further studies should include more donors as supplement and the results should be interpreted as complementary data to future data analyzed by performing the loop experiment using blood from patients.

INTRODUCTION: Acute infusion reactions from antineoplastic agents can include hypersensitivity reactions, anaphylaxis, and cytokine release infusion reactions. Severe acute infusion reactions happen in about 5% of the oncology patient population and nurses are responsible for assessment and management of the reaction. This is a high-stress task for a nurse magnified by the lack of exposure. This project explores nursing knowledge and perceived comfort level of acute infusion reactions caused by antineoplastic agents. METHODOLOGY: An original survey was created to test nursing knowledge and assess comfort level. Nursing knowledge was broken down into six subscales: general knowledge of acute infusion reactions, signs and symptoms of hypersensitivity, anaphylaxis, and cytokine release infusion reaction, and drugs most likely to cause hypersensitivity and anaphylactic reactions and cytokine release infusion reactions. Comfort questions were asked on a 6-point Likert scale from extremely uncomfortable to extremely comfortable. There was an additional section in the survey related to nurses’ distress and support in situations with acute infusion reactions. The questions were presented using a 6-point Likert scale ranging from strongly disagree to strongly agree. There were two open-ended questions that were designed to allow the nurses to share any additional information about their experiences with acute infusion reactions. Oncology nurses working with adults and pediatric populations were invited to participate. Descriptive statistics were used to analyze the survey results. T tests were used to compare groups and Pearson R statistics were used to examine relationships between total knowledge, knowledge subscale score, and comfort level. RESULTS: 20 nurses completed the survey. 12 were from the adult nurse population and 8 were from the pediatric nurse population. The typical participant was forty-four years of age, had sixteen years experience as a Registered Nurse, and thirteen years experience in the oncology setting. The average total knowledge score was a 56% based on 84 possible points. The basic knowledge section and the anaphylactic signs and symptoms were the highest scoring subscales, both scoring a 62%. Cytokine release infusion reaction signs and symptoms was the lowest scoring subscale with a 45%. There were no significant differences in knowledge between groups. The nurses chose an overwhelming agree/strongly agree when asked to choose the signs and symptoms related to each type of infusion reaction. The total comfort level score indicated that nurses were very comfortable managing acute reactions. There was no significant difference between the adult and pediatric setting comfort level scores. There was no statistically significant relationship between total knowledge score and total comfort level score. DISCUSSION: The knowledge score showed knowledge deficits while the comfort score indicated confidence in management of acute infusion reactions. The high frequency of agree/strongly agree for all three subscales of signs and symptoms indicates that the nurses at least know what to look for even if they cannot assign the specific sign and symptom to the type of infusion reaction. Knowledge about signs of specific types of drug reactions may not be necessary as long as a basic understanding of what to look for and how to manage a reaction is present.