Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial.
Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.
Attal
M
M
Department of Hematology, Chu Purpan, Toulouse, France.
Huguet
F
F
Rubie
H
H
Charlet
J P
JP
Schlaifer
D
D
Huynh
A
A
Laurent
G
G
Pris
J
J
D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D004361:Drug Tolerance; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies
D010431:Pentoxifylline