The Impact of Tocilizumab Treatment for Cytokine Release Syndrome on the Incidence of Blood Stream Infections after Peripheral Blood Haploidentical Hematopoietic Cell Transplantation

Abstract

Introduction: Cytokine release syndrome (CRS) is a potentially fatal systemic inflammatory response that can occur in patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT). IL-6 inhibitors, such as tocilizumab, are effective therapy in moderate to severe cases. Several studies have shown there to be a significant increase in infections with the use of tocilizumab in patients with rheumatoid arthritis, where it is given on a long term basis unlike in the post-haplo-HCT setting, where tocilizumab is rarely given for more than a few days. Severe CRS has been associated with increased infection risk in prior studies. However, the effect of anti-IL-6 therapy on infection risk has not been well established in the early haplo-HCT setting.In this study, we examined the effect of tocilizumab for treatment of CRS on the incidence of blood stream infections (BSIs) in the early post peripheral blood haplo-HCT setting.Patients and Methods: We performed a retrospective analysis of 235 patients who underwent T cell-replete peripheral blood haplo-HCTs from 2013 to 2020, stratified on CRS grade (graded by Lee criteria) and tocilizumab administration, for incidence of BSI. Positive blood cultures during days +2 to +28 post-haplo-HCT were included. Patients with positive blood cultures during the immediate peri-transplant period (days -5 to +1) were excluded as infection preceded CRS and tocilizumab administration. Patients who had positive blood cultures within 48 hours of CRS diagnosis were excluded as sepsis cannot be distinguished from CRS.Results: The overall incidence of bloodstream infection was 17% with 41 out of the total 235 patients having positive blood cultures. Patients with mild CRS had lower incidence of infection than patients with severe CRS (OR 0.31, 95% CI 0.13-0.74, p=0.0086). In the tocilizumab group, 31% (15/49) of patients had positive blood cultures compared with 14% (26/186) in the non-tocilizumab group (OR 1.61, 95% CI 0.30-8.60, p=0.58). However, after controlling for CRS grade, tocilizumab administration was not associated with higher rates of BSIs for any grade of CRS.Conclusions: Severe CRS after haplo-HCT is associated with higher risk of early BSI. However, tocilizumab therapy does not further increase risk of BSI in the early post-haplo-HCT setting. These data suggest that tocilizumab, a potentially life saving therapy, can be given without increasing risk of blood stream infections after haplo-HCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.