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Incidence, timing, and histologic grade of acute rejection in small bowel transplant recipients
Incidence, Timing, and Histologic Grade of Acute Rejection in Small Bowel Transplant Recipients D.L. Sudan, S. Kaufman, S. Horslen, I. Fox, B.W. Shaw Jr, and A. Langnas
I
N AN ATTEMPT to better understand immunologically mediated events following intestinal transplantation we retrospectively examined our experience with acute rejection in small bowel transplant recipients with attention to the incidence, timing, and severity. We further compared the results of isolated small bowel (ISB) and combined liver/small bowel (LSB) grafts to identify any differences.
METHODS A retrospective review was performed of all intestinal transplant recipients at the University of Nebraska Medical Center between September 1990 and April 1999. Demographic information was collected from hospital and office charts. Acute rejection episodes were identified by reviewing all pathology reports from intestinal transplant biopsies. Intestinal transplant recipients underwent protocol endoscopic biopsies twice weekly for the first 4 to 6 weeks after transplantation and with decreasing frequency thereafter. The histologic criteria used to make the diagnosis of acute intestinal allograft rejection has been previously described.1 Most intestinal transplant recipients were maintained on tacrolimus and prednisone for baseline immunosuppression. Initial target tacrolimus trough levels were 20 to 30 ng/dL. In seven patients, cyclosporine was administered in combination with prednisone. Statistical analysis included Student’s t test for comparison of means.
RESULTS
Small bowel transplantation was performed in 83 recipients, including isolated small bowel grafts in 35 patients and combined liver small bowel grafts in 48 patients. Eight recipients with patient or graft survival less than 7 days were excluded from further analysis. The demographic characteristics of these remaining 75 patients are summarized in Table 1. A total of 196 episodes of acute rejection of the small bowel allograft were identified in 65 of the 75 intestinal transplant recipients analyzed. Acute rejection was therefore identified in 87% of intestinal transplant recipients overall. There was no difference in the incidence of rejection between recipients of an isolated small bowel graft compared with a combined liver/small bowel graft (93% vs 82%, respectively; P ⫽ NS). Likewise, the mean number of acute rejection episodes was the same regardless of the type of allograft (ISB ⫽ 2.7 ⫾ 2.4 vs LSB ⫽ 2.5 ⫾ 2.1; P ⫽ NS).
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 32, 1199 (2000)
Table 1. Demographic Characteristics of 75 Intestinal Transplant Recipients at the University of Nebraska Medical Center With Patient and Graft Survival >7 Days
Adults Children (age ⬍16 years) Men Women Median follow-up (days)
Isolated Small Intestine (n ⫽ 30)
Liver/Small Intestine (n ⫽ 45)
8 22 16 14 442
2 46 25 20 412
Examination of the timing of rejection episodes revealed that, overall, 88% of rejection episodes occurred during the first year after intestinal transplantation (ISB 93% vs LSB 85%, P ⫽ NS). The median time to the first rejection episode was 15 days after transplantation (ISB 15 days vs LSB 16 days, P ⫽ NS). Seventy-two percent of intestinal transplant recipients experienced early acute rejection (within the first 30 days after transplantation) and 31% of recipients experienced late acute rejection (beyond the first year after transplantation). The severity of acute rejection was labeled mild in 80% of episodes. However, in 12 ISB recipients and 19 LSB recipients, acute rejection was identified as moderate or severe on at least one biopsy. Mortality in these 31 patients was 48%. Antilymphocyte therapy was used to treat steroidresistant rejection in 18 recipients. There was no difference in need for antilymphocyte therapy based on type of allograft (ISB 7 of 30, LSB 11 of 45; P ⫽ NS). In summary, the incidence of intestinal allograft rejection at our center was 87% and we did not find any protective benefit from liver transplantation in terms of the incidence, timing or severity of acute rejection of the intestinal allograft. REFERENCES 1. Sudan DL, Kaufman SS, Shaw BW Jr, et al: Am J Gastroenterol (in press) From the Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA. Address reprint requests to Dr Debra L. Sudan, Department of Surgery, 983285 Nebraska Medical Center, Omaha, NE 681983285.
0041-1345/00/$–see front matter PII S0041-1345(00)01182-9 1199
I
N AN ATTEMPT to better understand immunologically mediated events following intestinal transplantation we retrospectively examined our experience with acute rejection in small bowel transplant recipients with attention to the incidence, timing, and severity. We further compared the results of isolated small bowel (ISB) and combined liver/small bowel (LSB) grafts to identify any differences.
METHODS A retrospective review was performed of all intestinal transplant recipients at the University of Nebraska Medical Center between September 1990 and April 1999. Demographic information was collected from hospital and office charts. Acute rejection episodes were identified by reviewing all pathology reports from intestinal transplant biopsies. Intestinal transplant recipients underwent protocol endoscopic biopsies twice weekly for the first 4 to 6 weeks after transplantation and with decreasing frequency thereafter. The histologic criteria used to make the diagnosis of acute intestinal allograft rejection has been previously described.1 Most intestinal transplant recipients were maintained on tacrolimus and prednisone for baseline immunosuppression. Initial target tacrolimus trough levels were 20 to 30 ng/dL. In seven patients, cyclosporine was administered in combination with prednisone. Statistical analysis included Student’s t test for comparison of means.
RESULTS
Small bowel transplantation was performed in 83 recipients, including isolated small bowel grafts in 35 patients and combined liver small bowel grafts in 48 patients. Eight recipients with patient or graft survival less than 7 days were excluded from further analysis. The demographic characteristics of these remaining 75 patients are summarized in Table 1. A total of 196 episodes of acute rejection of the small bowel allograft were identified in 65 of the 75 intestinal transplant recipients analyzed. Acute rejection was therefore identified in 87% of intestinal transplant recipients overall. There was no difference in the incidence of rejection between recipients of an isolated small bowel graft compared with a combined liver/small bowel graft (93% vs 82%, respectively; P ⫽ NS). Likewise, the mean number of acute rejection episodes was the same regardless of the type of allograft (ISB ⫽ 2.7 ⫾ 2.4 vs LSB ⫽ 2.5 ⫾ 2.1; P ⫽ NS).
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 32, 1199 (2000)
Table 1. Demographic Characteristics of 75 Intestinal Transplant Recipients at the University of Nebraska Medical Center With Patient and Graft Survival >7 Days
Adults Children (age ⬍16 years) Men Women Median follow-up (days)
Isolated Small Intestine (n ⫽ 30)
Liver/Small Intestine (n ⫽ 45)
8 22 16 14 442
2 46 25 20 412
Examination of the timing of rejection episodes revealed that, overall, 88% of rejection episodes occurred during the first year after intestinal transplantation (ISB 93% vs LSB 85%, P ⫽ NS). The median time to the first rejection episode was 15 days after transplantation (ISB 15 days vs LSB 16 days, P ⫽ NS). Seventy-two percent of intestinal transplant recipients experienced early acute rejection (within the first 30 days after transplantation) and 31% of recipients experienced late acute rejection (beyond the first year after transplantation). The severity of acute rejection was labeled mild in 80% of episodes. However, in 12 ISB recipients and 19 LSB recipients, acute rejection was identified as moderate or severe on at least one biopsy. Mortality in these 31 patients was 48%. Antilymphocyte therapy was used to treat steroidresistant rejection in 18 recipients. There was no difference in need for antilymphocyte therapy based on type of allograft (ISB 7 of 30, LSB 11 of 45; P ⫽ NS). In summary, the incidence of intestinal allograft rejection at our center was 87% and we did not find any protective benefit from liver transplantation in terms of the incidence, timing or severity of acute rejection of the intestinal allograft. REFERENCES 1. Sudan DL, Kaufman SS, Shaw BW Jr, et al: Am J Gastroenterol (in press) From the Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA. Address reprint requests to Dr Debra L. Sudan, Department of Surgery, 983285 Nebraska Medical Center, Omaha, NE 681983285.
0041-1345/00/$–see front matter PII S0041-1345(00)01182-9 1199