Preventive OKT3 treatment with cyclosporine (Sandimmun) for second kidney transplantation

Abstract A total of 793 kidney transplantations (KTx) were performed from November 1073 to March 1993. Two hundred and forty-two patients were treated with conventional immunosuppression (azathioprine + prednisolone) and all the others with cyclosporine (Sandimmun) and prednisolone (SIM + PRED). The survival of the second graft was less good in both therapeutic groups than that of the first ones, so we have started to use preventive immunotherapy with OKT3 (CILAG) in combination with SIM (both before operation) and PRED. We compared 32 SIM-PRED patients with 20 OKT3 + SIM + PRED patients. All underwent a second KTx. The two groups were found to be comparable and homogeneous with regard to 14 of 18 parameters analysed statistically. Statistically significant differences were found between the two groups as regards the frequency of acute rejection within 30 days (46.69% vs 20%), the delta creatinine value on the 1st and 2nd postoperative days (- 4,3: -8 vs -8.6: -19.7%), patient survival after 4 years (78.2 vs 100%), and graft survival after 1 and 4 years (-58.9: -42.8 vs -83.5: -83.5%), with better results in the OKT3 group. We conclude that the preventive use of OKT3 simultaneously with SIM + PRED for the second KTx is the method of choice to prevent rejection and improve survival. This treatment results in patient and graft survival following the second KTx being as good as after the first KTx with SIM + PRED.     

OKT3 monoclonal antibody in heart transplantation

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.     

使用抗淋巴制剂治疗难治性排斥反应的临床观察

目的观察抗胸腺细胞球蛋白（ＡＴＧ）和单克隆抗体ＣＤ３（ＯＫＴ３）对难治性排斥反应的疗效。方法８７例患者,其中ＡＴＧ组１３例,平均治疗总量１０００ｍｇ;ＯＫＴ３组７４例,平均治疗总量４５ｍｇ。结果ＡＴＧ组对急性加速性排斥反应治愈２例;对急性排斥反应治愈７例;总有效率为６９２３％（９／１３）。ＯＫＴ３组对急性加速性排斥反应治愈率为９０００％（２７／３０）;对急性排斥反应治愈率为９０４７％（３８／４２）;总有效率为９０２８％（６５／７２）与ＡＴＧ组有显著性差异（Ｐ＜００５）。其中对再次移植患者的各种急性排斥反应有效率为９１６７％（１１／１２）。结论ＯＫＴ３治疗难治性排斥反应的效果优于ＡＴＧ,尤其对再次移植患者,但对慢性排斥反应患者无效     

Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection

Acute steroid-resistant rejection episodes are recommended to be treated with set doses of anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid-resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re-rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (micromol/L) was similar in the two groups (ATG/OKT3: before rejection 157 +/- 72/151 +/- 88, at start of antibody treatment 308 +/- 125/330 +/- 94, end of antibody treatment 254 +/- 122/246 +/- 144 and at follow-up after a mean of 32 months 166 +/- 55 (n = 24)/164 +/- 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 +/- 151 mg (2.3 administrations, range 1-4) and average OKT3 was 32.5 +/- 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.     

Orthotopic liver transplantation following heart transplantation]

Heart transplantation was performed in a 24-year-old man suffering from dilated cardiomyopathy who was also infected with hepatitis B virus and had not yet seroconverted. Most likely due to the immunosuppression, the hepatitis exacerbated and soon led to hepatic dystrophy and precoma. In this phase of congruent rejection of the heart transplant, liver transplantation was performed. During the procedure the patient had stable circulatory parameters and a reduced cardiac output. The heart rate and cardiac output stabilized after release of the anastomosis of the hepatic vessels. The patient survived for 6 months and died at home with signs of a myocardial infarction.     

Low-dose OKT3 induction therapy following renal transplantation: a controlled study

In a prospective clinical study we tested the immunosuppressiveproperties and toxicity of low-dose OKT3 induction therapy inrenal transplant recipients. 50 consecutive renal transplantrecipients were alternat ingly assigned to low-dose OKT3 inductionor prednisolone/cyclosporin. Low-dose OKT3 induction treatmentconsisted of 0.5 mg OKT3 twice daily for 10 days, initiallycombined with azathioprine and prednisolone maintenance immunosuppressionthat was converted to prednisolone/cyclosporin at the end ofthe course. During a 15–29-month follow-up period, low-doseOKT3 induction therapy was found to reduce significantly theincidence of acute rejections, as com-pared to the usual prednisolone/cyclosporinmainten ance immunosuppression (21 versus 52%, P=0.02). Therealso was a tendency towards an improved graft function afterlow-dose OKT3, although no signific ance was reached. Furthermore,compared to a histor ical control group of renal transplantpatients in whom acute rejection was treated with 5 mg OKT3daily, low-dose OKT3 appeared to cause fewer side-effects. Weconclude that low-dose OKT3 induction therapy is superior toprednisolone/cyclosporin in preventing acute rejection afterrenal transplantation and that it is better tolerated than conventionalOKT3 treatment.     

OKT3 treatment for steroid-resistant acute rejection in kidney transplantation

Orthoclone (OKT3, Ortho Biotech Inc, USA) monoclonal antilymphocyte antibody is a powerful T-cell-specific immunosuppressive agent. OKT3 has been used for induction therapy in kidney and liver transplantation, as well as to treat acute or steroid-resistant acute rejection episodes (ARE). This study was a retrospective analysis of 43 renal transplant recipients who developed steroid-resistant ARE and were treated with OKT3 between September 1994 and June 2004. The recipients were 36 men and 7 women of mean age 32.7 +/- 11.6 years (range, 19 to 48 years). The mean time from transplantation to OKT3 treatment was 7.2 +/- 6.7 months. Thirty-four episodes (79.1%) responded to OKT3 therapy with improved graft function, but the remaining 9 (20.9%) grafts did not respond. Among the 34 OKT3 responders, the mean serum creatinine decreased from 3.96 +/- 2.5 mg/dL to 2.45 +/- 1.77 mg/dL after treatment. Eleven (25.6%) of the 43 patients experienced minor side effects: fever, dyspnea, tachycardia, bradycardia. One patient (2.3%) developed acute pulmonary edema; one (2.3%), cytomegalovirus infection; and eight (18.6%), bacterial infections. The 1-, 3-, and 5-year graft survival rates for the 34 patients who responded to OKT3 therapy were 96%, 93%, and 85%, respectively. All patients are currently alive. The results indicate that OKT3 is a safe, effective treatment choice for steroid-resistant ARE in kidney transplantation.     

The use of OKT3 in steroid-resistant rejections following cadaveric kidney transplantation

OKT3 has been proved to be effective in the treatment of steroid-resistant rejection after renal allograft transplantation [1]. We investigated the clinical course of OKT3 recipients to find out in which cases of steroid resistance OKT3 therapy might be ineffective.     

Induction therapy for pediatric and adult heart transplantation: comparison between OKT3 and daclizumab

BACKGROUND: Induction therapy can reduce morbidity and early mortality in pediatric and adult heart transplant recipients. Monoclonal and polyclonal agents are most widely used; they nonspecifically deplete the T-cell pool and are thus associated with drug-induced side effects. The cytokine release syndrome is one of the most problematic events associated with induction. Daclizumab, a highly humanized, specific interleukin-2 receptor blocker, may be efficacious to the monoclonal agent, OKT3. Due to its specific action and properties, the safety profile of this agent may be superior to OKT3. METHODS: Forty subjects received daclizumab and their clinical outcomes were compared against a historical group of 40 subjects who received OKT3. Three- and six-month outcome measures included survival, rejection history, steroid burden, and complications. RESULTS: Mortality was low between the groups with equivalent 6-month survival. No differences in rejection profile or time to the first significant rejection event were detected; no subject had severe acute rejection within the first 180 days. Steroid requirement for maintenance immunosuppression and treatment of rejection was also similar between the groups. Six-month prevalence for complications were significantly different; 55% of OKT3-treated subjects having at least one event compared to 33% of daclizumab-treated subjects (P=0.04). The likelihood of complications occurred within the first month after transplantation. CONCLUSIONS: Daclizumab induction therapy is as efficacious as OKT3 in the prevention of early acute rejection after heart transplantation among pediatric and adult subjects. Complications related to the induction agent are significantly lower in the humanized product.     

Inotropic treatment in heart transplantation]

The safe conduct of anesthesia and intensive care for heart transplant recipient requires a sound understanding of the pathophysiology of advanced cardiac failure through knowledge of anesthetic and cardiovascular pharmacology and an appreciation of the altered physiologic and pharmacologic responses of acutely denervated and transplanted heart. The most serious dysfunction is acute distension and failure of the transplanted heart's right ventricle. Hemodynamic monitoring and TEE are useful in the management of inotropic support during heart transplantation.     

The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation

Zimmerman MA, Kelly MA, Campsen J, Mandell MS, Wachs M, Bak T, Skibba A, Lancaster B, Kam I. The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation.
Clin Transplant 2010: 24: E103–E108.
© 2009 John Wiley & Sons A/S. Abstract: Introduction:  Cancer recurrence following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is a significant obstacle in up to 10–20% of recipients. Recent evidence suggests that anti‐CD3 antibody (OKT3) therapy may be associated with increased rates of HCC recurrence. Methods:  At the University of Colorado Transplant Center, 173 patients underwent OLT for end‐stage liver disease with concomitant HCC between 1997 and 2008. Nine clinical and pathologic variables were analyzed to test the association between OKT3 therapy for steroid‐resistant rejection (SRR) and HCC recurrence‐free survival. Results:  Overall, the rate of HCC recurrence in this cohort was low and comparable across treatment groups (8.7%). Multivariate analysis reveals that increasing tumor diameter and differentiation have a negative impact on HCC recurrence‐free survival. Conclusions:  While several pathologic variables appear to influence outcome, we found no association between OKT3 therapy for SRR and HCC recurrence or survival.     

Prevention of cytomegalovirus infection following heart transplantation]

Cytomegalovirus (CMV) infection after heart transplantation (HTx) is a severe complication, which leads to long treatment and hospital stay. Even if prophylactic therapy with anti-CMV IgG antibodies is performed, there is a high incidence of infection, especially when the heart from a CMV positive donor is transplanted to a CMV negative recipient (high risk constellation). This study evaluates the prophylactic antiviral therapy with ganciclovir in CMV high risk constellation at HTx. Out of 108 HTx, 29 CMV negative recipients (IgG and IgM) received a heart from a CMV positive donor (IgG pos., IgM neg.). The control group (CO) (n = 8) was treated with anti-CMV IgG antibodies (Cytotect 2 ml/kg at day 0, 1, 2, 7, 14, 21,), whereas the study group (GAN) (n = 13) was treated with ganciclovir (7.5 mg/kg single dose n = 8, or 5 mg/kg in twice daily doses n = 5 from day 1 to 14). Urea, creatinine, white blood cell count and platelet count was controlled daily. No side effects on renal and bone marrow function were noted. Therapy was well tolerated. Both groups had similar immunosuppressive protocol (prophylactic cytolysis, prednisone, azathioprine and cyclosporin A) and were similar in age, sex, preoperative diagnosis and NYHA class. Seroconversion for CMV (IgM and IgG) was observed in 75% of CO and 31% of GAN (p less than 0.05). Clinical manifestations of CMV infection started in the second month after HTx with fever in both groups CMV-organ manifestations developed in 50% (or 67% of infected) in CO (enterocolitis 2, pneumonitis 3, tonsillitis 1), and in 15% (or 50% of infected) in GAN (pneumonitis 2, epididymitis 1) NS.(ABSTRACT TRUNCATED AT 250 WORDS)