Basiliximab Decreases the Incidence of Acute Rejection After Intestinal Transplantation D.L. Sudan, S. Chinnakotla, S. Horslen, K. Iyer, I. Fox, B. Shaw Jr, and A.N. Langnas
NTESTINAL allografts are highly immunogenic and have required higher levels of baseline immunosuppression than other solid organ transplant recipients to maintain graft function. In spite of much higher overall immunosuppression, approximately 80% to 90% of recipients experience rejection of the intestinal allograft and require additional bolus corticosteroid therapy or antilymphocyte therapy.1 Up to 20% of recipients require removal of the allograft due to uncontrollable acute rejection.2 The high levels of immunosuppression lead to frequent infectious complications. The addition of other immunosuppressive medications (such as OKT3, cyclophosphamide, and mycophenolate mofetil) has historically not resulted in a lower incidence of graft rejection or graft loss but has been associated with a higher incidence of infection.3 In kidney transplant recipients, basiliximab has been associated with a decreased incidence of acute rejection without an apparent increase in infectious complications.4,5 Herein we examine the efficacy of basiliximab in addition to standard immunosuppression with tacrolimus and steroids after intestinal transplantation. METHODS Group 1 included 65 consecutive primary intestinal allograft recipients treated with tacrolimus and steroid immunosuppression who survived for ⬎7 days after transplantation (historic controls). Group 2 consisted of 22 consecutive intestinal transplant recipients who received two doses of basiliximab (12 mg/m2) in addition to the dual-drug regimen of tacrolimus and
steroids, and had at least 3 months of follow-up. The first dose of basiliximab was given immediately after reperfusion of the intestinal allograft in the operating room and the second dose was administered on postoperative day 4. All patients underwent protocol endoscopy with biopsy, and acute rejection was defined using histologic criteria as previously described. The median ages of recipients in groups 1 and 2 were 2 and 3.9 years, respectively. The type of allograft was isolated small bowel in 28 and 3 recipients in groups 1 and 2, respectively, and combined liver and small bowel in 37 and 19 recipients in groups 1 and 2, respectively.
The incidence of acute rejection was markedly decreased by the addition of basiliximab to standard immunosuppression, as was the median number of episodes of rejection per patient. At 1 year posttransplant, 68% (95% CI 46% to 90%) of the patients receiving basiliximab remained free from rejection, whereas 18% (95% CI 8% to 27%) of the controls remained free from rejection. There was also a delayed onset of first rejection episodes in the group that received basiliximab (Table 1). There was no increase in the incidence of infectious complications in group 2 with the addition of basiliximab. In From the University of Nebraska Medical Center, Nebraska Health Systems, Omaha, Nebraska, USA. Address reprint requests to Dr D. Sudan, University of Nebraska Medical Center, Omaha, NE 68198.
Table 1. Incidence and Timing of Acute Rejection After Intestinal Transplantation in Patients With Standard Immunosuppression (Group 1) and With Basiliximab in Addition to Standard Immunosuppression (Group 2)
Number of patients with AR Median number of AR episodes
Group 1 (65 Patients)
Group 2 (22 Patients)
56 (86%) 3
8 (36%) 0
Severity of AR Total episodes of AR Mild rejection Moderate rejection Severe rejection Median time to first rejection (d) Number of patients with AR within 30 days Median follow-up
0041-1345/02/$–see front matter PII S0041-1345(02)02681-7 940
269 239 (89%) 18 (7%) 12 (4%) 15 47 (84%) 1146 days
10 8 (80%) 2 (20%) 0 38 2 (25%) 350 days
© 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 940 –941 (2002)
BASILIXIMAB FOR ACUTE REJECTION
Table 2. Assessment of Infectious Complications After Intestinal Transplantation With and Without Basiliximab Therapy
Viral infections Fungal infections Bacterial infections
Group 1 (65 patients)
Group 2 (22 patients)
39 (60%) 20 (31%) 92%
9 (41%) 3 (14%) 81%
NS NS NS
fact, there was a trend toward a decreased incidence of, infection primarily with regard to viral and fungal infections.
The results of intestinal transplantation lag behind those of other solid organ transplants due primarily to the increased risk of rejection and the high levels of immunosuppression required to prevent or control rejection episodes. Herein we have demonstrated that the addition of basiliximab decreases the incidence of rejection. The decreased need for supplemental immunosuppression for the treatment of rejection combined with the avoidance of antilymphocyte therapies is likely the reason for the trend toward decreased infectious complications in group 2. With a larger number of patients, this will most likely lead to an improved survival rate as well.
Basiliximab, in addition to baseline tacrolimus and prednisone immunosuppression, leads to a significant decrease in the incidence and median number of acute rejection episodes experienced after intestinal transplantation. In sharp contrast to the addition of other agents for immunosuppression of intestinal transplant allografts, there is no evidence of an increase in infectious complications. REFERENCES 1. Sudan DL, Kaufman S, Horslen S, et al: Transplant Proc 32:1199, 2000 2. Sudan DL, Kaufman SS, Shaw BW Jr, et al: Am J Gastroenterol 95:1506, 2000 3. Pinna AD, Weppler D, Nery JR, et al: Transplant Proc 32:1193, 2000 4. Nashan B, Moore R, Amlot P, et al: Lancet 350:1193, 1997 5. Kahan BD, Rajagopalan PR, Hall M: Transplantation 67:276, 1999