scholarly journals Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 732-736 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
JP Charlet ◽  
D Schlaifer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Randomized Trial ◽  
Marrow Transplantation ◽  
Group Versus ◽  
Prospective Randomized Trial ◽  
Tnf Alpha ◽  
Control Group ◽  
Group V ◽  
Significant Difference

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.

scholarly journals Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 732-736 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
JP Charlet ◽  
D Schlaifer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Randomized Trial ◽  
Marrow Transplantation ◽  
Group Versus ◽  
Prospective Randomized Trial ◽  
Tnf Alpha ◽  
Control Group ◽  
Group V ◽  
Significant Difference

Abstract 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.

Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial.

1991 ◽  
Vol 9 (5) ◽  
pp. 865-870 ◽  
Author(s):  
M Attal ◽  
D Schlaifer ◽  
H Rubie ◽  
F Huguet ◽  
J P Charlet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Randomized Trial ◽  
Marrow Transplantation ◽  
Group Versus ◽  
Prospective Randomized Trial ◽  
Empiric Antibiotic Therapy ◽  
First Episode ◽  
Control Group ◽  
Gram Positive

Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.

scholarly journals Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial [see comments]

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2834-2840 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
A Huynh ◽  
JP Charlet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Randomized Trial ◽  
Continuous Infusion ◽  
Marrow Transplantation ◽  
Low Dose ◽  
Control Group ◽  
Heparin Group ◽  
Dose Heparin ◽  
Low Dose Heparin

Abstract Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.

scholarly journals Phase I-II trial of pentoxifylline for the prevention of transplant- related toxicities following bone marrow transplantation [published erratum appears in Blood 1992 Jun 15;79(12):3397] [see comments]

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1205-1211 ◽  
Author(s):  
JA Bianco ◽  
FR Appelbaum ◽  
J Nemunaitis ◽  
J Almgren ◽  
F Andrews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Phase I ◽  
Marrow Transplantation ◽  
Hematologic Malignancies ◽  
Tnf Alpha ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Xanthine Derivative ◽  
Dose Levels

Abstract Disease relapse and transplant related toxicities have limited the application of bone marrow transplantation (BMT) in the treatment for hematologic malignancies. Because elevated levels of tumor necrosis factor alpha (TNF-alpha) have been correlated with the development of transplant related complications, we conducted a phase I-II trial of pentoxifylline (PTX), a xanthine derivative capable of down-regulating TNF-alpha production, in patients with hematologic malignancies undergoing BMT. Thirty consecutive adult patients (median age, 34) were entered and received either an allogeneic (n = 26) or autologous (n = 4) BMT. Patients were enrolled at increasing dose levels (1,200, 1,600, and 2,000 mg/d) from day -10 through day +100 posttransplant. PTX was well tolerated with no significant adverse side effects noted at any of the dose levels administered. The actuarial day 100 survival for these 30 patients was 90% (95% confidence interval 79% to 100%). When compared with a good risk control group, PTX recipients experienced less mucositis (3.7 +/- 1.1 v 18.7 +/- 1.1 days, P = .004), less hepatic venocclusive disease (10% v 65%, P = .001), a lower incidence of renal insufficiency (3% v 65%, P = .0003), required less days of total parenteral nutrition (TPN) (24.0 +/- 1.3 v 35.0 +/- 2.4, P = .001) and were discharged from the hospital earlier than controls (day 26.0 +/- 1.8 v 37.0 +/- 3.8, P = .01). In addition the incidence of graft-versus-host disease (GVHD) greater than or equal to grade II was also reduced among the PTX recipients (35% v 68%, P = .03). PTX at doses in excess of 1,200 mg/d further reduced the severity of mucositis, and TPN requirements resulting in earlier hospital discharge than patients receiving 1,200 mg/d of PTX. In this study oral administration of PTX in doses up to 2,000 mg/d was well tolerated and associated with a reduction in morbidity and mortality in patients undergoing BMT. Prospective randomized trials are currently in progress to test these preliminary observations.

scholarly journals Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial [see comments]

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2834-2840 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
A Huynh ◽  
JP Charlet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Randomized Trial ◽  
Continuous Infusion ◽  
Marrow Transplantation ◽  
Low Dose ◽  
Control Group ◽  
Heparin Group ◽  
Dose Heparin ◽  
Low Dose Heparin

Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.

scholarly journals Phase I-II trial of pentoxifylline for the prevention of transplant- related toxicities following bone marrow transplantation [published erratum appears in Blood 1992 Jun 15;79(12):3397] [see comments]

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1205-1211 ◽  
Author(s):  
JA Bianco ◽  
FR Appelbaum ◽  
J Nemunaitis ◽  
J Almgren ◽  
F Andrews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Phase I ◽  
Marrow Transplantation ◽  
Hematologic Malignancies ◽  
Tnf Alpha ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Xanthine Derivative ◽  
Dose Levels

Disease relapse and transplant related toxicities have limited the application of bone marrow transplantation (BMT) in the treatment for hematologic malignancies. Because elevated levels of tumor necrosis factor alpha (TNF-alpha) have been correlated with the development of transplant related complications, we conducted a phase I-II trial of pentoxifylline (PTX), a xanthine derivative capable of down-regulating TNF-alpha production, in patients with hematologic malignancies undergoing BMT. Thirty consecutive adult patients (median age, 34) were entered and received either an allogeneic (n = 26) or autologous (n = 4) BMT. Patients were enrolled at increasing dose levels (1,200, 1,600, and 2,000 mg/d) from day -10 through day +100 posttransplant. PTX was well tolerated with no significant adverse side effects noted at any of the dose levels administered. The actuarial day 100 survival for these 30 patients was 90% (95% confidence interval 79% to 100%). When compared with a good risk control group, PTX recipients experienced less mucositis (3.7 +/- 1.1 v 18.7 +/- 1.1 days, P = .004), less hepatic venocclusive disease (10% v 65%, P = .001), a lower incidence of renal insufficiency (3% v 65%, P = .0003), required less days of total parenteral nutrition (TPN) (24.0 +/- 1.3 v 35.0 +/- 2.4, P = .001) and were discharged from the hospital earlier than controls (day 26.0 +/- 1.8 v 37.0 +/- 3.8, P = .01). In addition the incidence of graft-versus-host disease (GVHD) greater than or equal to grade II was also reduced among the PTX recipients (35% v 68%, P = .03). PTX at doses in excess of 1,200 mg/d further reduced the severity of mucositis, and TPN requirements resulting in earlier hospital discharge than patients receiving 1,200 mg/d of PTX. In this study oral administration of PTX in doses up to 2,000 mg/d was well tolerated and associated with a reduction in morbidity and mortality in patients undergoing BMT. Prospective randomized trials are currently in progress to test these preliminary observations.

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