A randomized placebo-controlled trial of lisofylline in HLA-identical, sibling-donor, allogeneic bone marrow transplant recipients. The Lisofylline Marrow Transplant Study Group.
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/microl and platelet recovery (>20 000/microl) 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.
List
A F
AF
Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-0524, USA.
Maziarz
R
R
Stiff
P
P
Jansen
J
J
Liesveld
J
J
Andrews
F
F
Schuster
M
M
Wolff
S
S
Litzow
M
M
Karanes
C
C
Dahlberg
S
S
Kirkhart
B
B
Bianco
J A
JA
Singer
J W
JW
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001521:Behavior Therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005069:Evaluation Studies as Topic; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007239:Infections / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010431:Pentoxifylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D010919:Placebos / Q000008:administration & dosage; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects; D014916:Whole-Body Irradiation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006680:HLA Antigens; D010919:Placebos; C025189:lisofylline; D010431:Pentoxifylline