Randomized, placebo-controlled, double-blind, multicenter trial of efficacy and safety of granulocyte colony-stimulating factor in liver transplant recipients

Background Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony- stimulating factor (G-CSF) to liver transplant recipients was associated wi th a decrease in sepsis episodes, sepsis-related deaths, and rejection comp ared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial. Methods. Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 mu g/day of G-CSF or 30 0 mu g/day of G-CSF. The study drug was started preoperatively and then con tinued after the transplant for a maximum of 21 days. Patients were evaluat ed for microbiologically-documented infection, biopsy-proven rejection, num ber of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events. Results. During the first 30 days after the transplant, the median peak whi te blood cell count was 16.5 x 10(9)/L, 34.6x10(9)/L, and 54.8x10(9)/L for the placebo, low dose G-CSF, and high-dose G-CSF patients, respectively. Th e incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pn eumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0 .056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically su spected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 pa tients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093), There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-C SF patients (18%) and 10 placebo patients (15%) who died within 120 days af ter the transplant. No serious adverse events were attributed to G-CSF, Conclusion. Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomia l pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CS F.