共查询到20条相似文献,搜索用时 0 毫秒
1.
D J Frey A J Matas K J Gillingham D Canafax W D Payne D L Dunn D E Sutherland J S Najarian 《Transplantation》1992,54(1):50-56
We prospectively studied the use of prophylactic Minnesota antilymphocyte globulin vs. OKT3 in kidney transplant recipients. Between 7/1/87 and 9/1/90, 138 adult kidney and 35 kidney-pancreas recipients were randomized after stratification for age (18-49 vs. greater than or equal to 50), diabetes (diabetic vs. nondiabetic), transplant number (1 vs. greater than 1) and, for retransplants, the length of survival of the first graft (less than 1 year vs. greater than or equal to 1 year), and then randomized to receive 7 days of either MALG (20 mg/kg/day) or OKT3 (5 mg/day). Immunosuppression was otherwise identical in both groups; prednisone and azathioprine started on the day of surgery, and cyclosporine started on postoperative day 6. Minimum follow-up was 9 months. There was no difference in one- and two-year actuarial patient or graft survival rates, incidence of rejection, or serum creatinine level. MALG was associated with a higher incidence of cytomegalovirus; it was statistically significant in the subgroup of CMV seronegative recipients of kidneys from seropositive donors (P less than .05). OKT3 was more expensive and was associated with significantly more side effects: fever (P less than .0001), dyspnea (P = .04), and acute respiratory distress syndrome (ARDS) (P = .02). 相似文献
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A randomized clinical trial comparing OKT3 and steroids for treatment of hepatic allograft rejection 总被引:1,自引:0,他引:1
A B Cosimi S I Cho F L Delmonico M M Kaplan R J Rohrer R L Jenkins 《Transplantation》1987,43(1):91-95
A multiinstitutional randomized trial was undertaken comparing OKT3 with steroids for treatment of hepatic allograft rejection. All patients received baseline immunosuppression with Cyclosporine (CsA) and steroids. At the time of biopsy-confirmed rejection, up to 2 intravenous boluses (250-1000 mg) of methylprednisolone were initially administered. Twenty-eight patients who failed to respond were then randomly assigned to OKT3 or continued steroid therapy. Rescue therapy with the opposite treatment arm was added after 6 days if the primarily allocated protocol failed. Three of 13 patients assigned to the steroid group responded promptly, and continue with good function 7-12 months later. OKT3 rescue was required in 10 patients who failed to improve despite receiving up to 6 g of methylprednisolone (mean: 3.3 g/patient). One patient died of sepsis and hepatic failure. Rejection was reversed in 9 OKT3-rescue patients, 7 of whom are well 1-17 months later. In the OKT3 group, improved allograft function was observed within 72 hr in 11 of 15 patients. Two patients with inadequate response were successfully rescued with steroids; 1 patient underwent retransplantation; and 1 patient developed a biliary fistula that eventually resulted in sepsis and death. In summary, 23 of 28 hepatic recipients (82%) are alive with the original allograft 1-17 (mean 7.8) months after treatment for acute rejection. Another patient is alive 14 months following retransplantation. Eighteen (78%) of the survivors required OKT3 as initial (11) or rescue (7) therapy, whereas only 5 were successfully managed with steroids. OKT3 is superior to steroids for reversing liver allograft rejection and has greatly reduced the need for retransplantation even in recipients selected on the basis of having failed initial steroid therapy. 相似文献
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R D Gordon A G Tzakis S Iwatsuki S Todo C O Esquivel J W Marsh A Stieber L Makowka T E Starzl 《American journal of kidney diseases》1988,11(2):141-144
Experience with the use of Orthoclone OKT3 monoclonal antibody for the treatment of acute cellular rejection in a series of 130 human orthotopic liver transplantations is reviewed. Treatment was highly effective in reversing rejection, in reducing the rate of retransplantation, and in lowering patient mortality. OKT3 was also useful for cyclosporine sparing in patients with poor renal function, hypertension, or CNS toxicity. There was a significant incidence of opportunistic infection associated with the use of OKT3. 相似文献
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Reexposure to OKT3 in renal allograft recipients 总被引:1,自引:0,他引:1
J T Mayes J R Thistlethwaite J K Stuart M R Buckingham F P Stuart 《Transplantation》1988,45(2):349-353
Between 40% and 80% of patients treated with the monoclonal antibody OKT3 develop blocking antibody against its idiotypic region. Thus a major concern with the use of OKT3 as part of a baseline immunosuppressive regimen is that formation of blocking antibodies might preclude its subsequent use. Between 7/86 and 2/87, 32 patients received prophylactic OKT3 in addition to low-dose prednisone, azathioprine, and cyclosporine. Prophylactic OKT3 did not prevent rejection, as 21 of 32 patients studied developed rejection. Retreatment of 13 patients with OKT3 successfully reversed 12 rejections and lowered the number of T3-positive cells in spite of a low level of blocking antibody in two patients in this group. Of the patients analyzed, 38% developed blocking antibody on initial exposure to OKT3, but OKT3 reuse was denied only 4 patients due to the presence of these antibodies. Three of these had rejections reversed with steroids alone; the other patient lost the allograft. A high frequency of infectious complications occurred in the retreatment group, with viral infections predominating. Only one patient in the retreated group developed antibodies after the second use. Appearance of blocking antibodies after use of OKT3 as part of a base-line prophylactic immunosuppressive regimen did not significantly compromise access to OKT3 for treatment of subsequent rejection episodes, but multiple exposures to OKT3 did increase the frequency of infectious complications. 相似文献
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S L Wee D M Stroka F I Preffer L K Jolliffe R B Colvin A B Cosimi 《Transplantation》1992,53(3):501-507
Significant differences in cellular responses were found among allograft recipients treated with various OKT4A mAb protocols. Recipients of multiple infusion low-dose and 2-bolus OKT4A immunosuppressive regimens regularly showed potent donor-specific cytotoxic CD8+ and CD4+ intragraft T cells and donor-reactive PBMC in MLC tests. In contrast, PBMC isolated from recipients of high-dose OKT4A therapy generally showed very weak or no response to donor-antigens during the later posttransplant periods. Furthermore, an absence of IL2-responsive intragraft cells was found to correlate with stable graft function in these recipients. We conclude that OKT4A mAb, in high doses, can block allosensitization and induce donor-specific nonresponsiveness in vivo. An OKT4A-based therapy, therefore, may have the potential of inducing long-lasting donor-specific immunosuppression, or even tolerance. 相似文献
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R J Stratta M S Shaefer K A Cushing R S Markin E C Reed A N Langnas T J Pillen B W Shaw 《Archives of surgery (Chicago, Ill. : 1960)》1992,127(1):55-63; discussion 63-4
The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n = 50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing non-cytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis. 相似文献
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J R Thistlethwaite A B Cosimi F L Delmonico R H Rubin N Talkoff-Rubin P W Nelson L Fang P S Russell 《Transplantation》1984,38(6):695-701
OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1-5 mg daily for a period of 10-21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cells subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2-8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20-44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6-17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection. 相似文献
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D Abramowicz M Goldman L De Pauw J L Vanherweghem P Kinnaert P Vereerstraeten 《Transplantation》1992,54(3):433-437
We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n = 56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n = 52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P less than 0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P less than 0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P less than 0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P = 0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P = 0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation. 相似文献
9.
J B Klein K R McLeish C M Bunke B Chang B L Ganzel A D Slater L A Gray 《Transplantation》1988,45(4):727-729
OKT3 is a murine monoclonal antibody that recognizes the T3 surface antigen present on mature T cells, and it has been used to successfully treat renal allograft rejection. We report our experience with OKT3 in the treatment of cardiac allograft rejection. Eight patients with endomyocardial biopsy evidence of moderate or severe rejection were given fourteen daily intravenous treatments of OKT3. Six of the eight patients had complete recovery following OKT3 therapy; one required additional steroid therapy for recurrence and one patient failed to respond. Five of the six patients with a complete response have experienced no further rejection (mean follow-up 437 days). Adverse reactions to OKT3 were common early in the treatment course, but were well tolerated. We concluded that OKT3 is a safe and effective treatment of cardiac allograft rejection and that a majority of patients experience long-term rejection-free periods. 相似文献
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M R Bristow E M Gilbert J B O'Connell D G Renlund F S Watson E Hammond R G Lee R Menlove 《American journal of kidney diseases》1988,11(2):135-140
OKT3 monoclonal antibody (OKT3) has already proved to be a valuable edition to the immunosuppression armamentarium available in cardiac transplantation. It is highly effective in treating refractory rejection, where approximately 90% of subjects may be salvaged. It may be even more valuable in prophylaxis, where in combination with an antibody suppression strategy and low-dose, "delayed" cyclosporine it appears to afford near complete protection against rejection. Moreover, OKT3-based prophylaxis seems to impact favorably on the rejection rate after the prophylaxis course has been completed. Adverse reactions are common and generally manageable, although occasional serious clinical events do occur. 相似文献
11.
M H Deierhoi W H Barber J J Curtis B A Julian R G Luke S Hudson B O Barger A G Diethelm 《American journal of kidney diseases》1988,11(2):86-89
The monoclonal antibody OKT3 (Ortho Pharmaceutical, Raritan, NJ) was utilized in two separate protocols for treatment of acute renal allograft rejection in patients receiving cyclosporine, azathioprine, and prednisone for maintenance immunosuppression. In Group I, 54 patients received steroids for primary treatment of acute rejection with OKT3 used for resistant rejections and second rejection episodes. In Group II, 34 patients received OKT3 as primary treatment of acute rejection while steroids were used for rescue and second rejection episodes. OKT3 successfully reversed 82% of initial acute rejection episodes in Group II as compared with a 63% reversal with steroids in Group I. Rescue treatment was required in only 15% of Group II patients compared with 33% of Group I patients. Overall patient survival was 96% and 94%, respectively, for steroid primary and OKT3 primary treatments. Allograft survival at 3 months was identical, 74% in both groups. Based on allograft survival data, OKT3 is equally effective either as primary treatment for allograft rejection, or for rescue therapy if initial corticosteroid treatment fails. 相似文献
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Prophylactic use of OKT3 monoclonal antibody in cadaver kidney recipients. Utilization of OKT3 as the sole immunosuppressive agent 总被引:4,自引:0,他引:4
P Vigeral N Chkoff L Chatenoud H Campos M Lacombe D Droz G Goldstein J F Bach H Kreis 《Transplantation》1986,41(6):730-733
We describe the first clinical trial of OKT3, a monoclonal anti-T-cell antibody, for prevention of kidney transplant rejection. 13 patients receiving a first cadaveric kidney transplant were randomly assigned to conventional treatment with azathioprine and high-dose steroids (7 patients) or to treatment with daily injection of OKT3 alone (6 patients). The first OKT3 injection resulted in a dramatic decrease in T3+, T4+, and T8+ cells, while patients simultaneously experienced fever, chills, and diarrhea. These symptoms did not recur with subsequent injections. All six OKT3-treated patients had a rejection necessitating introduction of steroids 12.8 +/- 2.9 days after surgery. Rejection was related to appearance of anti-OKT3 antibodies leading to disappearance of detectable OKT3 in the serum. Modulating (T3-, T4+ or T3-, T8+) cells were observed in all patients but were functionally inactive. As no rejection was observed before day 9 posttransplant, despite the lack of additional immunosuppressive agents, we conclude that OKT3 is a powerful, well-tolerated immunosuppressive agent. However, it is highly immunogenic and anti-OKT3 antibodies lead to loss of clinical effectiveness in this protocol. The use of OKT3 alone for prevention of kidney graft rejection cannot be recommended until a method for reducing the effects of anti-OKT3 immunization is developed. 相似文献
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A Debure N Chkoff L Chatenoud M Lacombe H Campos L H No?l G Goldstein J F Bach H Kreis 《Transplantation》1988,45(3):546-553
Fifty-five recipients of first cadaveric renal allografts were randomly assigned to three treatment groups in order to compare the safety and efficacy of a mouse antihuman T cell monoclonal antibody (OKT3) given prophylactically for a one-month period. This long period of administration was made possible by concomitant administration of azathioprine. The immune response against the foreign immunoglobulin was thus delayed and decreased in both intensity and severity, and OKT3 treatment could be given during almost the entire month in the majority of patients. The 18 patients who were enrolled in this treatment group had significantly (P less than 0.01) fewer rejection episodes during the first month posttransplantation than the 19 patients allocated to the high-dose (HD) steroid control group or the 18 patients allocated to the low-dose (LD) control group. Actual 2-year as well as actuarial 4-year graft survival rates were 89% in the OKT3 group, whereas they were 70% and 67% respectively in the steroid control groups. Four-year serum creatinine levels were normal and doses of steroids and other immunosuppressive agents were lower in the OKT3 group as compared with the control groups. Tolerance to OKT3 was good, and while viral infections were more frequently observed in OKT3 treated patients, the total number and the severity of infectious episodes were similar in all groups. The combination of one-month OKT3 plus azathioprine prophylaxis followed by conventional azathioprine plus low-dose steroid maintenance produced very satisfactory long-term results comparable to the best results now being obtained with cyclosporine regimens. 相似文献
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Abdelmalek MF Humar A Stickel F Andreone P Pascher A Barroso E Neff GW Ranjan D Toselli LT Gane EJ Scarola J Alberts RG Maller ES Lo CM;Sirolimus Liver Conversion Trial Study Group 《American journal of transplantation》2012,12(3):694-705
A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression. 相似文献