Cyclosporine Administration and Graft Versus Host Disease: Continuous Intravenous Infusion vs. Intravenous Bolus Dosing

Abstract

Introduction Continuous infusion (CIVI) cyclosporine (CSA) is an alternative for allograft recipients intolerant of twice daily infusions (TDI). Trough concentrations are an accepted surrogate for monitoring therapy, however total exposure may be dependent on peak concentrations not obtained when given via CIVI. Therefore, maintaining the same trough goals for both routes of administration may lead to decreased CSA exposure and subsequent increased rates of graft versus host disease (GVHD). The purpose of this study was to evaluate the incidence of acute GVHD and overall survival among patients receiving CIVI vs. TDI CSA. Methods We performed a retrospective study of adult patients undergoing first allogeneic HCT at the University of Minnesota Medical Center between 2011 and 2017 that received > 48 hours of CSA. All patients initially received CSA via TDI per institutional standard and targeted whole blood trough concentrations of 200-400 ng/mL via HPLC. Any change to CIVI was made at the discretion of the treating physician. All patients were changed to oral CSA when able. Patients were grouped according to administration method; those that received cyclosporine via CIVI for > 48 hours at any time during initial transplant admission were classified as CIVI and those that received CSA exclusively as TDI were classified as TDI. Results 308 patients met inclusion criteria (CIVI 42, TDI 266). Donor type, GVHD prophylaxis, underlying diagnosis, and conditioning intensity were similar between groups. The majority of subjects received HLA-matched sibling or cord blood allografts. There were an equal proportion of myeloablative and reduced intensity conditioning regimens, and nearly all GVHD prophylaxis therapy consisted of cyclosporine combined with either mycophenolate or methotrexate. Forty two patients received CSA via CIVI for > 48 hours for a median of 9 days (range, 3-32 days). The average time of change from TDI to CIVI was 3 days after transplant. The TDI group received only TDI for a median 17 days (range 4-62 days) prior to conversion to oral CSA. CSA concentrations at day -1 and weeks 1, 2, and 3 were similar between the groups (Figure 1). We found no difference between the rates of grade II-IV acute (45% vs 53%, p = 0.59) or chronic (17% vs 30%, p = 0.20) GVHD or overall survival (57% vs 67%, p = 0.10) between groups. Subgroup analysis of patients that received myeloablative conditioning did not reveal significant differences in GVHD or overall survival. Conclusion In contrast to previous studies, we did not observe an association of CIVI CSA administration with acute GVHD. Among patients intolerant of bolus CSA infusions, a brief transition to CIVI CSA appears to be a safe and acceptable route of administration without increased risk of GVHD or adverse effects on overall survival.