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 undergoing allogeneic bone marrow transplantation (bmt). we performed a multicenter, randomized placebo-controlled trial in 60 patients with hematologic malignancies receiving bmt from hla-identical sibling donors. patients were 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 discharge. 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 ⩾1, age ⩾40 years, and prior exposure to cmv. nausea and vomiting were the only adverse events observed in a higher proportion of lsf-treated patients that led to study withdrawal in six of 42 patients (14%). the times to neutrophil recovery to ⩾500/μl and platelet recovery (>20 000/μl) were not improved by LSF treatment. Nevertheless, no patient who received treatment with 3 mg/kg LSF developed a documented infection between day 0 and 35 or had a serious or fatal 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 treatment with LSF 3 mg/kg reduced the incidence of infections and improved 100-day survival in patients receiving related-donor allogeneic bone marrow transplantation. Bone Marrow Transplantation (2000) 25, 283–291.