Evaluation of OKT3 monoclonal antibody and anti-thymocyte globulin in the treatment of steroid-resistant acute allograft rejection in pediatric renal transplants

We reviewed the effectiveness of Muromonab-CD₃ (OKT3) and anti-thymocyte globulin (ATG) in the treatment of corticosteroid-resistant acute renal allograft rejection in 49 transplanted children. Reversal of rejection was successful in 22 of 23 patients (96%) treated with OKT3 and 21 of 26 (81%) treated with ATG (P=NS). Re-rejection episodes occurred within 1 month of cessation of therapy in 9 of 22 patients treated with OKT3 but only in 2 of 21 who received ATG (P<0.05). In the patients with re-rejection, 7 of the 9 patients originally given OKT3 and 1 of the 2 who received ATG responded to a repeat course of high-dose corticosteroids; thus, at 1 month post treatment, the incidence of graft loss due to initial rejection or re-rejection was 13% for the OKT3 and 23% for the ATG group (P=NS). Graft survival was similar at 6 months: 82% for OKT3- and 73% for ATG-treated patients (P=NS); 100% patient survival was noted in both groups. Mean calculated creatinine clearance prior to, during, and at 1 and 6 months post rejection was similar in the OKT3- and ATG-treated groups. Neutropenia and thrombocytopenia occurred more frequently in the ATG group, but there was no significant difference in infectious complications. Two patients developed high (1:1,000) OKT3 antibody titers. In our experience, children with corticosteroid-resistant acute renal allograft rejection treated with OKT3 and ATG had similar allograft survival and level of renal function at 1 and 6 months, and number of infectious complications post therapy.     

A randomized prospective study comparing low-dose OKT3 to low-dose ATG for the treatment of acute steroid-resistant rejection episodes in kidney transplant recipients

Acute steroid-resistant rejection episodes in kidney allograft recipients require treatment with antilymphocyte antibodies. Monoclonal anti-CD3 and polyclonal antilymphocyte antibodies have been widely used but seldom compared. Recent data have suggested that these antibodies could be used at reduced doses without jeopardizing their efficacy. In this study, we randomized renal transplant recipients who encountered a first acute steroid-resistant rejection episode to low-dose ATG or low-dose OKT3 treatment. Sixty patients were enrolled in the study. They received prophylactic immunosuppression with cyclosporin, azathioprine, and prednisolone. Treatment of biopsy-proven rejection consisted of a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was 484 ± 110 mg, i. e., 0.75 mg/kg per day. The total OKT3 dose was 32 ± 4 mg, i. e., 0.05 mg/kg per day. We compared reversion of rejection, side effects, immunodepression, and graft function. Reversion of rejection was similar in the two groups, although we noted a trend in favor of ATG. Results were 3 % vs 10 % early graft failures, 13 % vs 23 % overall graft failures, 28 % vs 38 % 3-month actuarial incidence of rebound rejection, and 89 % vs 81 % 1-year graft survival rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3 group due to the first-dose syndrome. Infections and cancers occurred with the same frequency. ATG resulted in a deeper and longer decrease in peripheral lymphocyte subsets. Graft function was similar in the two groups. We conclude that low-dose ATG and low-dose OKT3 are equally effective in reversing steroid-resistant acute rejection. Tolerance was better with ATG, which also gave a more potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3 did not appear to lessen their efficacy. Received: 27 June 1997 Received after revision: 15 October 1997 Accepted: 19 November 1997     

OKT3 serum levels as a guide for prophylactic therapy: a pilot study in kidney transplant recipients

The use of OKT3 as prophylaxis in renal transplantation results in a reduced incidence of graft rejection and appears to have beneficial effects on long-term kidney graft survival. However, we and others have observed that patients still experience rejection during the period of OKT3 prophylaxis given at the regular 5 mg/day dose. Many of these patients had no circulating CD3⁺ cells at the time of rejection, but their OKT3 serum levels were distinctly low (<500 ng/ml). This led us to adjust OKT3 doses (5 or 10 mg) daily, according to the patients' OKT3 levels, in order to maintain an OKT3 concentration of around 1000 ng/ml. In addition, patients were randomized to receive either 5 mg (group 1, n=15) or 10 mg (group 2, n=14) OKT3 as the initial three doses. Concomitant immunosuppression consisted of azathioprine and steroids, with the introduction of cyclosporin A on day 11. Patient survival was 100% after 3 months of follow-up. The intensity of OKT3 first-dose reactions was similar in both groups. Intragraft thrombosis, initially observed in a previous group of patients who received a fixed 10 mg/day OKT3 prophylaxis, occurred in three patients in group 1 and resulted in two graft losses. The cumulative OKT3 dose was similar in both groups (mean ± SEM 98±2 mg in group 1 vs 102±3 mg in group 2) and higher than the 70 mg usually administered. Group 2 patients had higher OKT3 serum levels during the first 4 days of therapy. No correlation could be found between patient weight and cumulative OKT3 dose (r=0.29). No patient in either group 1 or 2 experienced rejection during OKT3 therapy. This compared favorably with an historical group of kidney recipients treated with a fixed 5 mg/day OKT3 dose, as 6 out of 32 patients in this group developed rejection (P=0.045). The rejection rate up to 3 months post-transplantation in pooled group 1 and 2 patients was low (six episodes per 81 patientmonths of risk exposure). We conclude that adaptation of the OKT3 dose according to daily OKT3 levels is safe and allows for excellent prevention of early graft rejection.     

High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study

In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.     

Reversal of acute glomerular renal allograft rejection: a possible effect of OKT3

A major cause of renal allograft loss is glomerulovascular rejection. This case report is about an episode of histologically proven acute glomerular rejection that was successfully reversed. Monoclonal antibody OKT3 may have been the effective agent.     

The risk of infection following OKT3 and antilymphocyte globulin treatment for renal transplant rejection: results of a single center prospectively randomized trial

Some 43 of 60 (72%) renal allograft recipients who were prospectively randomized to receive either OKT3 monoclonal antibody (n = 30) or ALG (antilymphocyte globulin) polyclonal antibody (n = 30) for steroid-resistant rejection suffered from infection, 25 (83%) following OKT3 and 18 (60%) following ALG treatment (P < 0.05). Clinically evident herpes infection was most frequently seen (9 and 7, respectively), followed by pneumonia (6 and 1, respectively P < 0.05), urinary tract infection and wound infection (2 of each in both groups) fungal (Candida) and multibacterial infections. One patient died in each group due to cytomegalovirus (CMV) pneumonia, giving a mortality of 4.3% in each group. Actuarial 1-year graft and patient survival rates were 80% and 97% in both groups, respectively. It is concluded that ALG and OKT3 are equally effective in renal allograft rejection resistant to steroid treatment, however, the risk of infection appears to be higher with OKT3.     

Antithymocyte globulin use for treatment of biopsy confirmed acute rejection is associated with prolonged renal allograft survival

Antithymocyte globuline (ATG) and OKT3 have been used for treatment of severe biopsy confirmed acute renal allograft rejection (BCAR). We report results on graft and patient survival including 399 subjects diagnosed with BCAR treated with either ATG or OKT3. Multivariable analyses including Banff scores were performed following three different strategies to account for confounding variables. Fifty per cent of subjects in the OKT3 group had a functioning graft 6.3 years after diagnosis of BCAR, but 74% of ATG patients' grafts were still functioning at that time point (log rank P  = 0.006). Median actual graft survival was only 4.6 years in the OKT3 subjects, but 9.5 years for ATG-treated patients (log rank P  = 0.004). Multivariable analysis revealed that the risk for functional graft loss was significantly elevated in the OKT3 compared to ATG patients (HR = 1.79, 95% CI 1.06–3.02, P  = 0.029). The risk for actual graft loss, counting death as event, was also significantly elevated in the OKT3 patients (HR = 1.73, 95% CI 1.09–2.74, P  = 0.019). The hazard of death was not different between the groups (HR = 1.55, 95% CI 0.87–2.77, P  = 0.137). These data suggest that rejecting renal allografts treated with ATG exhibit longer graft survival than OKT3 treated transplant kidneys. Causal inference, however, cannot be drawn from this associational study.     

达利珠单抗和OKT3预防肾移植术后急性排斥反应的比较

目的　比较达利珠单抗和OKT3预防肾移植术后早期急性排斥反应的效果。方法　肾移植受者在使用环孢素A(或他克莫司 )、霉酚酸酯及激素预防急性排斥反应的基础上加用达利珠单抗 (42例 )或OKT3(12 8例 ) ,观察 2个组肾移植术后 3个月内急性排斥反应发生率。结果　肾移植术后 3个月内 ,使用达利珠单抗者急性排斥反应发生率为 2 .4 % ,明显低于使用OKT3者的13.3% (P <0 .0 5 ) ,且前者无耐激素者 ,急性排斥反应的发生时间推迟 ,血肌酐恢复正常的时间也早于使用OKT3者。结论　达利珠单抗预防肾移植术后急性排斥反应的效果优于OKT3。     

Reversal of acute glomerular renal allograft rejection: a possible effect of OKT3

Abstract. A major cause of renal allograft loss is glomerulovascular rejection. This case report is about an episode of histologically proven acute glomerular rejection that was successfully reversed. Monoclonal antibody OKT3 may have been the effective agent.     

Improved renal allograft survival in children treated with FK 506 (tacrolimus) rescue therapy

FK 506 has been reported to be effective in reversing acute renal allograft rejection that is resistant to steroids and to OKT3. The contribution of FK 506 “rescue” therapy to long-term graft survival has not been determined. We report 23 children transplanted between January 1993 and December 1994, 10 of whom received FK 506 “rescue” therapy. Acute rejection was reversed in 8 of 10, with 7 of the remaining grafts still functioning after a mean follow-up of 10.9±7.8 (SD) months (range 1 – 26 months). The actuarial 1-year graft survival rate was 86% compared with 66% for historical controls (P <0.05). We conclude that FK 506 may provide long-term benefits to children facing allograft loss due to acute rejection. Received August 15, 1995; received in revised form and accepted April 1, 1996     

Increase of sTNF receptor levels in acute renal allograft rejection after treatment with OKT3

The use of OKT3 is associated with severe clinical side-effects.Adverse reactions are partly attributed to release of tumournecrosis factor (TNF). TNF binds to two receptors on the outermembranes of most human cell lines. Shedding of these proteins(sTNFR-p55 and sTNFR-p75) may block biological effects of TNF.Here we show a fair correlation between serum levels of sTNFRsand renal function as measured by glomerular filtration rate(GFR). In addition we assessed levels of sTNFR-p55 and sTNFRp75, corrected for reduced renal clearance, in renal allograftrejection and following treatment with OKT3. Corrected serumlevels (CSL) of sTNFR-p55 and sTNFR-p75 were determined in 12renal allograft patients treated for an acute rejection episodewith either OKT3 or methylprednisolone (MPNS). Serum levelsof CSLsTNFR-p55 and CSLsTNFR-p75 in both groups prior to anti-rejectiontreatment were not elevated. CSLsTNFRs peaked at 1 h after theadministration of OKT3, whereas in the MPNS group CSLsTNFRsremained unchanged. We conclude that in acute renal transplantrejection CSLsTNFRs increase after treatment with OKT3. In spiteof high circulating sTNFRs levels all OKT3-treated patientssuffered from clinical side-effects.     

Soluble tumor necrosis factor-receptors are not a useful marker of acute allograft rejection: a study in patients with renal or cardiac allografts

In this study, we investigated soluble tumor necrosis factor receptor (sTNF-R) levels in plasma of patients with either a kidney or cardiac allograft when clinical suspicion of acute rejection was raised. In plasma of patients with acute renal graft rejection, the sTNF-R levels were strongly enhanced (20–150 ng/ml) as compared to plasma of patients with stable renal function. Following successful treatment of the rejection, a gradual decline in sTNF-R levels occurred with improving renal function, and an inverse correlation between creatinine clearance and sTNF-R was found. To determine whether the increase was caused by an accumulation of constitutively released sTNF-R and lack of clearance by the kidney, or whether the immunological process of the rejection caused the enhancement, we measured sTNF-R in patients suffering from acute cardiac graft rejection but with predominantly stable kidney function. Rejection of a cardiac graft did not lead to a significant enhancement of sTNF-R levels. However, treatment with ATG or OKT3 did cause enhanced sTNF-R levels, followed by a decline that reached starting values after 7 days. These results provide evidence that the immune reaction that occurs during rejection of a graft does not per se induce discernible changes in sTNF-R levels, whereas that induced by ATG or OKT3 does. Thus, sTNF-R levels are not a reliable marker in transplant recipient monitoring.     

OKT3 induction in pediatric renal transplantation

Twenty cadaveric renal transplant patients (mean age 12.5±4.8 years) received 14 days (mean 13.0±2.8 days) of OKT3 (mean dose 0.16±0.09 mg/kg) along with prednisone 0.5 mg/kg per day, azathioprine 2 mg/kg per day and cyclosporine 5 mg/kg per day which was increased to obtain therapeutic levels before the discontinuation of OKT3. Actuarial patient and graft survival were 100% and 50%, respectively, at both 1 and 5 years. Four children lost their grafts within the first 48 h. One loss was technical in origin, the remaining 3 had pathological evidence of vascular thrombosis. Of the remaining 16 children, 12 (75%) experienced rejection episodes within the first 2 months post transplant (mean 27±15 days). Successful reversal of early rejection episodes was achieved in 11 of 12 patients. Clinically significant cytomegalovirus infection occurred in 4 patients and resulted in graft loss in 2 patients. Circulating OKT3 levels ranging from 1,000 to 32,000 ng/ml were seen in all patients within the first 48 h. There was a rapid and total depletion of circulating CD3-positive lymphocytes in all patients. Antiisotypic and anti-idiotypic OKT3 antibodies were assessed by enzyme-linked immunosorbent assay (ELISA), and blocking anti-idiotypic antibodies were detected by immunofluorescence inhibition assay. Positive OKT3 antibody titers were detected in 11 children by ELISA and 10 children by immunofluorescence inhibition assay. In summary, we have found that in pediatric renal transplant patients receiving OKT3 induction therap: (1) there is a high occurrence of vascular thrombosis; (2) the incidence of early acute rejection is high; (3) the time to first rejection is not as long as that reported for adults; (4) there is a substantial rate of sensitization against OKT3; (5) despite successful reversal of early acute rejection, long-term-graft survival does not appear to have been beneficially altered.     

Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n = 100) with peak panel reactive antibody (PRA) levels > 30%, who received cadaveric renal transplants between 1/1/'90 and 12/31/'95 at our institution, were divided into FCXM + and FCXM - groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM + patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM + patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM - patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM + and FCXM - patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM + cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients.     

肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究

目的 观察肾移植1年后发生急性排斥反应时移植肾组织中补体片段C4d的表达情况,分析其对移植肾功能及预后的影响.方法 选择肾移植时间超过1年,临床诊断为急性排斥反应并经病理穿刺活检证实的肾移植受者36例为研究对象.以第1例受者移植肾组织穿刺时间为观察起点(2006年3月),以此项研究结束时间为观察终点(2010年4月).应用C4d多克隆抗体对移植肾穿刺组织行免疫组织化学染色,检测C4d在移植肾组织中的表达情况;根据检测结果,分为C4d阳性组和阴性组,分析和比较两组在观察时间段内移植肾功能的变化及存活时间.结果 在36例受者的移植肾穿刺标本中,C4d阳性16例(44.4%),C4d阴性20例(55.6%);C4d阳性组和阴性组移植肾组织中嗜酸性粒细胞浸润数量分别为(9.4±4.5)个和(2.6±1.8)个,两组比较,差异有统计学意义(P＜0.05).在观察时间段内,所有受者血清肌酐均有不同程度上升,但C4d阳性组上升幅度与C4d阴性组比较,差异无统计学意义(P＞0.05);C4d阳性组和C4d阴性组受者移植肾功能丧失率分别为31.3%(5/16)和30.0%(6/20),两组比较,差异无统计学意义(P＞0.05).C4d阳性组和C4d阴性组受者移植肾穿刺后的巾位存活时间分别为(19.3±5.3)个月和(22.5±7.4)个月,两组比较,差异无统计学意义(P＞0.05).结论 肾移植1年后发生急性排斥反应时,移植肾组织中C4d表达阳性对其功能及存活时间无明显影响.     

Rescue therapy with tacrolimus (FK 506) in renal transplant recipients —a Scandinavian multicenter analysis

All renal allograft recipients (n = 32) in Sweden and Norway who were converted from cyclosporin(CyA)-based immunosuppression to FK 506 (tacrolimus) between October 1992 and June 1995 were analyzed retrospectively. The reasons for conversion were acute refractory rejection (n = 21), chronic rejection (n = 4), and suspected CyA toxicity (n = 6); one patient was converted for psychological reasons. The mean time from transplantation to conversion was 29 (range 1–243) weeks and there was a mean follow-up of 46 (2–143) weeks. Overall graft survival was 59%, with graft survival 52% in patients converted because of acute rejection, 50% in patients converted because of chronic rejection, and 83% in patients converted because of CyA toxicity. There was no significant correlation between preconversion serum creatinine and outcome. Seventy-two percent of the patients had significant side effects during FK 506 treatment, the most frequent ones being neurological and gastrointestinal symptoms. These improved after dose reduction. Two patients became overimmunosuppressed and developed lymphoma. One patient died of the primary kidney disease, hemolytic uraemic syndrome. We conclude that FK 506 therapy is able to salvage kidneys with acute refractory rejection and that it is an alternative in patients with CyA toxicity. However, the risk of overimmunosuppression must be considered.     

A randomized prospective trial of OKT3 induction in the current immunosuppression era

Recent improvements in immunosuppression and subsequent decreases in the incidence of acute rejection have brought into question the benefit of the use peri-transplant antibody therapy (i.e. induction therapy). In the current era of immunosuppression that includes mycophenolate mofetil (MMF) and cyclosporine emulsion (Neoral, Novartis, Basle, Switzerland), we designed and have completed a prospective, randomized trial to address this question. Cadaveric and living donor renal allograft recipients were randomized to receive either OKT3/MMF/delayed Neoral/prednisone or MMF/immediate Neoral/prednisone without OKT3. The incidence of rejection episodes was the primary end point. Patients with delayed graft function were excluded. All rejection episodes were biopsy proven and all patients have been followed for a minimum of 2 yr. Fifty-four patients received OKT3 induction, of which 6 patients suffered a rejection episode (11%), while 13 patients (27%) not receiving OKT3 (p=0.04) had a rejection episode. Four patients in the no OKT3 group suffered multiple rejections, while there were only 2 with more than one episode in the OKT3 group. There was no increased incidence of infectious complications in the group receiving OKT3. Hospital costs tended to be higher in the OKT3-treated group, but were not significantly different. The low incidence of rejection in the OKT3-treated group was intriguing and validates the use of antibody therapy in the early post-operative periods even in the era of improved baseline immunosuppression.     

Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation

SUMMARY:   Simultaneous pancreas–kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte-depleting therapy is associated with a high incidence of side-effects. We performed a historical controlled trial to compare OKT3 versus anti-CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty-eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 ( n  = 12) and basiliximab was used after ( n  = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100 vs 100%), kidney (91.7 vs 91.7%) and pancreas (75 vs 83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximab vs 25% on OKT3, P  = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 ± 11.9 vs 54.5 ± 15.9 mL/min for  basiliximab vs OKT3, P  < 0.001). The incidence of major opportunistic infection was lower in basiliximab-treated patients (9 vs 50% in the OKT3 group, P  = 0.033). Basiliximab was associated with similar 6-month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.     

OKT3 treatment of steroid-resistant renal allograft rejection

The monoclonal antibody, Orthoclone OKT3 (OKT3), has been used with great efficacy in a prospective multicenter trial as therapy for first rejection episodes in cadaveric donor (CD) renal allograft recipients treated with azathioprine (AZA) and prednisone (P). However, although almost all rejection episodes were reversed, recurrent rejection occurred in approximately two-thirds of OKT3-treated patients in this earlier trial; infections also occurred in about two-thirds of patients, often related to the additional immunosuppression necessary to reverse the rerejection episodes. In the current series of patients, OKT3 was used to treat rejection in CD renal graft recipients in a protocol differing from the multicenter trial in two respects: baseline immunosuppression was cyclosporine (CsA) and P or CsA, AZA, and P (probably more potent immunosuppressive combinations than the AZA and P in the multicenter trial); and OKT3 treatment was reserved for rejection episodes resistant to 3 bolus infusions of methylprednisolone (MP), 5-10 mg/kg, rather than as primary therapy for first rejection episodes. Using this protocol, 46 of 74 rejection episodes (62%) diagnosed between 3/85 and 3/86 in CD renal allograft recipients were treated successfully with MP. Of the remaining 28 steroid-resistant rejection episodes, 27 (96%) were reversed with a 7-14-day course of OKT3, 5 mg/day. Only 5 recurrent rejection episodes (19%) have been observed in the 2-14-month follow-up period after OKT3 treatment; infections have occurred in 10 patients (36%), and three grafts (11%) have been lost in OKT3 treated patients. These results suggest that recurrent rejection and subsequent infection after OKT3 is used to treat rejection may be reduced in a protocol where CD renal allograft recipients are treated with baseline immunosuppression regimens including CsA and where OKT3 is reserved for steroid-resistant rejection. This approach appears to be both more cost-effective than, and as effective therapeutically as, treating all first rejection episodes with the monoclonal antibody.     

OKT3治疗移植肾难治性排斥反应

为了解ＯＫＴ３对移植肾难治性排斥反应的治疗效果，１９９３年１月至１９９６年６月，我们对４４例肾移植术后移植肾难治性排斥反应（其中加速性排斥反应７例，急性排斥反应３７例）应用ＯＫＴ３治疗。结果：６例加速性排斥反应及３１例急性排斥反应逆转，总逆转率为８４．６％。２５例对ＯＫＴ３治疗产生迅速反应，平均逆转时间为７±４天，１２例发生延迟性反应，平均逆转时间为３４±３天（Ｐ＜０．０１）。作者认为：ＯＫＴ３治疗难治性排斥反应效果显著。巨细胞病毒感染及细胞因子释放综合征是ＯＫＴ３治疗的主要副作用。患者对ＯＫＴ３治疗的延迟性反应与细胞因子释放综合征及排斥损害有关。产生低滴度抗ＯＫＴ３抗体的患者可再次接受ＯＫＴ３治疗。