A randomized placebo-controlled trial of lisofylline in HLA-identical, sibling-donor, allogeneic bone marrow transplant recipients

The purpose of the study was to evaluate the effect of lisofylline (LSF) on engraftment, regimen-related toxicities (RRT), and mortality in patients u ndergoing allogeneic bone marrow transplantation (BMT), We performed a mult icenter, randomized placebo-controlled trial in 60 patients with hematologi c malignancies receiving BMT from HLA-identical sibling donors. Patients we re randomized to receive either placebo, 2 mg/kg LSF or 3 mg/kg LSF every 6 h, beginning before conditioning and continuing to day 21 or hospital disc harge. Treatment groups were balanced with respect to conditioning regimen and disease stage. However, significantly more patients in the 2 mg/kg LSF group were at high risk for RRT due to performance status greater than or e qual to 1, age greater than or equal to 40 years, and prior exposure to CMV . Nausea and vomiting were the only adverse events observed in a higher pro portion of LSF-treated patients that led to study withdrawal in six of 42 p atients (14%), The times to neutrophil recovery to greater than or equal to 500/mu l and platelet recovery (>20 000/mu l) were not improved by LSF tre atment. Nevertheless, no patient who received treatment with 3 mg/kg LSF de veloped a documented infection between day 0 and 35 or had a serious or fat al infection between day 0 and 100 (P = 0.003 vs placebo for both). The day -100 survival rate was also significantly improved in the 3 mg/kg LSF group (89%), compared with either the 2 mg/kg LSF (48%) or placebo (61%) groups (log-rank test, 3 mg/kg LSF vs placebo, P = 0.026). We conclude that treatm ent with LSF 3 mg/kg reduced the incidence of infections and improved 100-d ay survival in patients receiving related-donor allogeneic bone marrow tran splantation.