F. Kriaa

Prophylactic use of the IL-2 receptor-specific monoclonal antibody LO-Tact-1 with cyclosporin A and steroids in renal transplantation.

LO-Tact-1 is a rat anti-human monoclonal antibody which is directed to the 55-kDa alpha-chain of the interleukin 2 (IL2) receptor. We conducted a pilot trial in 15 first-time cadaveric renal transplant patients undergoing for immunosuppression a 14-day course of LO-Tact-1 (10 mg i.v. daily) together with cyclosporine, low dose steroids (0.5 mg/kg) and azathioprine. Results showed a good immunosuppressive effect, as measured by the similar incidence of acute rejection episodes (0.6 per patient) when compared with 20 patients treated during the same period with our standard quadruple prophylactic combination with higher initial doses of steroids (2 mg/kg) and antilymphocyte globulin (ALG) instead of LO-Tact-1 (0.4 per patient). At 2 years post-transplant, graft survival was 93%, and only 1 patient lost his kidney by rejection. No local or general adverse effect of antibody administration was encountered, and haematological changes remained of minor importance. Local bacterial infection was observed in 3 patients, but viral diseases (including cytomegalovirus, CMV) remained exceptional. In contrast, severe clinical CMV infections occurred in 3 patients (15%) treated by ALG. Nine of 15 patients developed rat-specific antibodies, but only 4 before the completion of LO-Tact-1 treatment, without any correlation with the further development of acute rejection. Patients who suffered rejection had lower LO-Tact-1 levels and higher soluble IL2 receptor levels during the period of infusion, suggesting the crucial importance of pharmacokinetic monitoring to adjust individual doses.

Long‐term results (10 years) of a prospective trial comparing Lo‐tact‐1 monoclonal antibody and anti‐thymocyte globulin induction therapy in kidney transplantation

To evaluate long‐term patient and graft survival, and the incidence of acute and chronic rejection, infectious diseases and malignancies following induction therapy with a rat monoclonal interleukin 2 receptor antibody, Lo‐Tact‐1, or anti‐thymocyte globulin (ATG). Forty first‐time kidney transplant patients were prospectively randomized to two groups between May 1990 and June 1991. Twenty recipients were treated with Lo‐Tact‐1 (group 1) and the other 20, with ATG (group 2) during the first 14 days of the transplantation protocol. All patients were treated with azathioprine, steroids and cyclosporin A. Data were collected over 10 years. Median age was 42.1 years in group 1 and 39.3 years in group 2. Six recipients died during the 10 years of follow‐up. All had functioning grafts. Death‐censored graft survival was 35% in group 1 and 45% in group 2 after 10 years (P = NS). The number of acute rejection was similar in the two groups. Chronic allograft rejection was significantly more frequent in group 2 (n = 9) than in group 1 (n = 3), P < 0.05. Viral and bacterial infections were more frequent in group 2 than in group 1 (respectively 8 vs. 2 and 16 vs. 10, P < 0.05). Three patients had cancer. Although both Lo‐tact‐1 and ATG effectively prevented acute renal rejection, fewer bacterial and viral infections and cases of chronic allograft rejection were observed in Lo‐tact‐1‐treated patients after 10 years of follow‐up, demonstrating the potential value of this treatment for kidney transplantation.

Long-term results and risk factors of quadruple immunosuppression in renal transplantation

POLYCLONAL antilymphocyte globulins (ALGs) have been used in cadaver renal transplantation since 1960 for the prevention and treatment of acute allograft rejection. However, in the cyclosporine (CsA) era, their utility within multidrug immunosuppressive protocols has been debated. The rationale for biological agent induction is first to provide heavy initial immunosuppression to abrogate, delay, or reverse subsequent rejection episodes. Second, the use of ALG with delayed CsA introduction was advocated to minimize the potentially deleterious effects of CsA on cadaver transplants submitted with multiple (ie, ischemia–reperfusion) perioperative injuries. We have previously demonstrated that a quadruple association with a 14-day course of ALG, oral CsA from day 1, prednisolone, and delayed introduction of azathioprine (AZA) provided excellent results on short-term endpoints, such as 1-year graft survival, rejection incidence, and early complication incidence, without inducing overimmunosuppression complications. This study aimed to analyze long-term results (survival, complications, causes of failure, and risk factors for failure) in a cohort of 632 cadaver transplants performed at our institution from 1985 to 1997 using such protocol.