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Intestinal and Multivisceral Transplantation Immunosuppression Protocols—Literature Review
Intestinal and Multivisceral Transplantation Immunosuppression Protocols—Literature Review A.P. Trevizol, A.I. David, E.R. Dias, D. Mantovani, R. Pécora, and L.A.C. D’Albuquerque ABSTRACT Introduction. Currently the most used techniques for small bowel transplant are isolated intestinal transplantation, multivisceral transplantation (MVT), and modified multivisceral transplantation. One important factor is early diagnosis of acute cellular rejection (ACR). In addition, improvements in immunosuppression have recently reduced the number and enhanced treatment of ACR episodes, enabling graft recovery. Objective. We analyzed immunosuppression protocols of leading transplantation centers in the last 5 years. Method. We reviewed papers published in PubMed from major multivisceral and intestinal transplantation centers from 2006 to 2010 in adult recipients. The 211 adults transplanted in seven centers were divided into three groups according to the immunosuppression protocol used: protocol 1: daclizumab induction with tacrolimus and steroid maintenance; protocol 2: alemtuzumab and tacrolimus; and protocol 3: thymoglobulin and rituximab and tacrolimus. Results. Protocol 2 showed the lowest rate of ACR (34%). Protocols 1 and 3 displayed 54% and 48% ACR rates; respectively. However, protocol 1 patients developed only mild ACR, whereas those in protocols 2 and 3 developed moderate ACR in 26.3% and 11.7%, and severe ACR in 7.9% and 47% of cases, respectively. The infection rate was considerably lower in protocol 3 (7.4%). Protocols 1 and 2 showed infection rates of 62.5% and 52%, respectively. One-year patient survival rates were 70%, 79% and 81%, respectively. Three-year patient survival rates were 62%, 56%, and 78% for protocols 1, 2 and 3, respectively. Conclusion. Protocol 2 was the strongest immunosuppressive regimen capable of reducing ACR rates when compared with the other protocols, but the strong effect resulted in high infection rate that impacts 1-year patient survival. Protocol 3 seems to be the best available one balancing ACR and infection rates. NTESTINAL (IT) and multivisceral (MVT) transplantations are the only curative treatments for patients who have failure of the intestinal tract associated with lifethreatening complications due to parenteral nutrition. The first human bowel transplantation was performed in 1964 at the Boston Floating Hospital.1 Nearly 20 years later, the first human multivisceral transplant was performed at the University of Pittsburgh.2 The immunosuppressive protocol included cyclosporine; graft rejection and fatal infection blocked progress of the endeavor, which became feasible after the advent of tacrolimus in 1989.3 Intestinal expression of histocompatibility antigens, resident immune cells and microorganisms, as well as innate immunity make graft
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rejection and infection bigger problems than those observed with other solid organ transplantations.4,5 The immunosuppression protocols for IT and MVT must be strong to prevent acute cellular rejection (ACR), thus increasing the risk for infection, which is the main cause for
From the Faculdade de Ciências Médicas da Santa Casa de São Paulo (A.P.T., E.R.D., D.M.), and the GI Transplant Program, Hospital das Clinicas/FMUSP (A.I.D., R.P., L.A.C.D.), São Paulo, Brazil. Address reprint requests to André Ibrahim David, Rua Pamplona 1808, apto 52, Jardim Paulista, São Paulo, Brazil. E-mail: [email protected]
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.07.016
Transplantation Proceedings, 44, 2445–2448 (2012)
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TREVIZOL, DAVID, DIAS ET AL
Table 1. Patient Survival Rate Presented According to Author and Immunosuppression Protocol Author (y)
N
Protocol
Patient Survival Rate %, 1/3/5 years
Nishida (2006) Nishida (2006) Zanfi (2010) Zanfi (2010) Lauro (2006) Lauro (2006) Kimura (2008) Kimura (2008) Yuan-Xin (2010) Vianna (2008)
39 37 12 28 12 17 11 23 5 27
1 2 1 2 1 2 1 2 2 3
57/48/nd 70/47/nd 78/76/66 79/6/43 92/82/nd 82/64/nd 80/80/75 90/70/60 nd 81/78/nd
Abbreviation: nd, no data.
death. Patient and graft survival rates have improved using induction therapy to reduce ACR early postoperatively as well as the need for high maintenance tacrolimus doses. However, infectious complications are still the leading factor in recipient deaths because of the strong immunosuppression.6 An adequate immunosuppression protocol must balance ACR and infection rates. We sought to analyze the reported results from leading transplantation centers over the last 5 years attempting to evaluate the current protocol that achieved the best overall results. MATERIALS AND METHODS This review was performed using PubMed focusing on immunosuppressive protocols for intestinal and multivisceral transplantation. Articles published from 2006 to 2010 were selected7–12 according to the criteria of information about the outcomes of immunosuppressive protocols. We compared three protocols: protocol 1; daclizumab (2 mg/kg/wk for 3 months and 1 mg/kg/wk for another 3 months) for induction plus maintenance treatment with tacrolimus (trough concentration ⫽ 15 to 20 ng/dL) and steroids; protocol 2; alemtuzumab (0.3 mg/kg in four doses on postoperative days 0, 1, 3, and 7) for induction and maintenance treatment with tacrolimus (8 to 12 ng/mL); and protocol 3: thymoglobulin (rATG; 10 mg/kg divided into five equivalent doses of 2 mg/kg, on postoperative days 0, 2, 4, and 6) plus rituximab (150 mg/m2 as a single dose on postoperative day 3) as induction treatment and maintenance with tacrolimus (12 to 15 ng/dL). We compared infection, ACR and patient survival rates.
and 3 year values were 62.23%, 56%, and 78% for protocols 1, 2, and 3, respectively (Fig 1). DISCUSSION
IT and MVT became possible with improved immunosuppression protocols, particularly in the induction protocols. While minimizing ACR the main cause of graft loss, demands high levels of immunosuppression, it can regulates extremely high incidences of bacterial infections with sepsis as the main cause of death.13 We compared three immunosuppressive protocols used in these settings: Protocol 1 included daclizumab as induction immunosuppression, protocol 2, alemtuzumab, the effect of which lasts approximately 6 month and protocol 3, rituximab plus thymoglobulin, which has possible protective effects against reperfusion injury when administered before organ reperfusion.14 –16 Protocol 2 showed the lowest ACR rate (34%), probably due to the stronger degree of induction treatment. Protocol 1 despite a high rate only showed mild cases of ACR, whereas 26.3% and 7.9% were moderate and severe, in protocol 2, respectively. Protocol 3 had the greatest number of severe ACRs episodes (47%). The infection rate was lower in protocol 2 (52%) than protocol 1 (62.5%). The 1-year survival rate was better using protocol 2 (79%) versus protocol 1 (70%). When comparing protocols 2 and 3, we observed that, although protocol 3 showed a higher ACR rate than protocol 2 (48% vs 34%), with almost half of them being severe (47%), only 30% of the episodes occurred in the first 90 days posttransplantation. MVT patients experienced only one severe ACR, possibly due to the protective effect of massive removal of native lymphoid tissue. Infection, the main cause of death, was significantly lower with protocol 3 (7.4%) than protocol 2 (62.5%). Tzakis et al17 described the most common infection sites to be the blood stream and respiratory tract, followed by the wound and intra-abdominal cavity. Half of the patients with bacteremia had it associated with the catheter site. Oltean et al18 reported that the central venous catheter (CVC) was Table 2. ACR and Infection Rates Presented According to Author and Immunosuppression Protocol
RESULTS
A total of 211 adults were transplanted. Protocol 1 included 74 patients; protocol 2, 105; and protocol 3, 27 (Tables 1 and 2). We found that protocol 2 showed the lowest rate of ACR (34%) in contrast to protocols 2 and 3 with 54% and 48% ACR rates, respectively. Protocol 1 patients developed only mild ACR, whereas those in protocols 2 and 3, moderate ACR in 26.3% and 11.7% of cases with severe ACR in 7.9% and 47% of cases of ACR, respectively. Infection rates were considerably lower in protocol 3 (7.4%). Protocols 1 and 2 showed infection rates of 62.5% and 52%, respectively. One-year patient survival rates were 70%, 78.76%, and 81%
Author (y)
Protocol
ACR Rate %/n Patients/n Mild/n Moderate/n Severe
Nishida (2006) Nishida (2006) Zanfi (2010) Zanfi (2010) Lauro (2006) Lauro (2006) Kimura (2008) Kimura (2008) Yuan-Xin (2010) Vianna (2008)
1 2 1 2 1 2 1 2 2 3
nd nd 66/8/9/—/— 42/12/11/3/— 42/5/6/—/— 12/2/—/2/— nd nd 60/3/7/3/1 48/13/9/2/8
Abbreviation: nd, no data.
Infection Rate %/n Patients
nd nd 66/8 57/16 58/7 53/9 nd nd 20/ 7,4/2
IMMUNOSUPPRESSION PROTOCOLS
2447
Fig 1. (A) Patient survival rate, (B) ACR rate, and (C) infection rate by immunosuppression protocol.
the leading location of infections followed by respiratory, intra-abdominal, and wound infections. However, neither study separated infections by immunosuppressive protocol or time after the procedure. In 2009, Kimura et al19 studied the main sites and pathogens related to infections in protocols 1 and 2. In the first month after transplant, the leading sites of bacterial infections were wound and intra-abdominal (ascites), followed by CVC venous catheter and blood stream. The main pathogens were Escherichia coli and Pseudomonas aeruginosa in protocol 1; and Enterococcus, Klebsiella, and Pseudomonas aeruginosa in protocol 2. After that, the main sites of bacterial infections were CVC and blood stream in both protocols, followed by broncho-alveolar lavage in protocol 1 and wound in protocol 2. Pseudomonas aeruginosa was the main pathogen of bacterial infections in protocol 1, whereas various pathogens were observed in protocol 2: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis, and others. In addition, protocol 2 seemed to be associated with a prolonged duration of first infection when compared with protocol 1, probably due to the stronger induction therapy. All but two deaths that
occured in both protocols were related to infectious complications, including sepsis and cytomegalovirus enteritis. Cicalese et al20 proposed the use of living related donors to reduce bacterial infections after IT. However, several risks including short bowel syndrome, small bowel obstruction, dysvitaminosis, and diarrhea should be considered when using living donors. Moreover, the most important issue is to provide an adequate length of intestine to the recipient to ensure enteral autonomy while preserving sufficient small bowel length in the donor. Infection is still a big problem in IT and MVT due to the immunosuppressive protocol. In conclusion, protocol 2 engendered the strongest immunosuppression based upon low ACR rates compared with the other regimens. But this strong immunosuppression resulted in an high rate of infection, which affected 1-year patient survival. Protocol 3 seemed to be the best available immunosuppression protocol, which balanced between ACR and infection rates. REFERENCES 1. Kirkman RL: Small bowel transplantation. Transplantation 37:429, 1984
2448 2. Starzl TE, Rowe MI, Todo S, et al: Transplantation of multiple abdominal viscera. JAMA 261:1449, 1989 3. Starzl TE, Todo S, Fung J, et al: FK 506 for human liver, kidney and pancreas transplantation. Lancet 2:1000, 1989 4. Abu-Elmagd K: The history of intestinal transplantation. In: Nakim NS, Papalois VE(eds): The History of Organ and Cell Transplantation. London: Imperial College Press; 2003, 171 5. Abu-Elmagd K, Reyes J, Bond G, et al: Clinical intestinal transplantation: a decade of experience at a single center. Ann Surg 234:404, 2001 6. Grant D, Abu-Elmagd K, Reyes J, et al: 2003 report of the intestine transplant registry: a new era has dawned. Ann Surg 241:607, 2005 7. Nishida S, Levi DM, Moon JI, et al: Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients. Transplant Proc 38:1747, 2006 8. Zanfi C, Lauro A, Cescon M, et al: Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceraltransplantation: rejection and infection rates in 40 recipients during the early postoperativeperiod. Transplant Proc 42:35, 2010 9. Lauro A, Amaduzzi A, Dazzi A, et al: Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceraltransplantation: a comparison of two different regimens on 29 recipients during the earlypost-operative period. Dig Liver Dis 39:253, 2007. Epub 2007 Feb 1 10. Kimura T, Lauro A, Cescon M, et al: Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab. Clin Transplant 23:420, 2009 11. Yuan-Xin L, Ning L, You-Sheng L, et al: Preliminary experience with alemtuzumab induction therapy combined with
TREVIZOL, DAVID, DIAS ET AL maintenancelow-dose tacrolimus monotherapy in small-bowel transplantation in China. Transplant Proc 42:29, 2010 12. Vianna RM, Mangus RS, Fridell JA, et al: Induction immunosuppression with thymoglobulin and rituximab in intestinal andmultivisceral transplantation. Transplantation 85:1290, 2008 13. Jordan SC, Pescovitz MD: Presensitization: the problem and its management. Clin J Am Soc Nephrol 1:421, 2006 14. Beiras-Fernandez A, Chappell D, Hammer C, et al: Influence of polyclonal anti-thymocyte globulins upon ischemiareperfusion injury in a non-human primate model. Transplant Immunol 15:273, 2006 15. Bogetti D, Jarzembowski TM, Sankary HN, et al: Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy. Transplant Proc 37:404, 2005 16. Bogetti D, Sankary HN, Jarzembowski TM, et al: Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury. Clin Transplant 19:507, 2005 17. Tzakis AG, Kato T, Levi DM, et al: 100 multivisceral transplants at a single center. Ann Surg 242:480, 2005 18. Oltean M, Herlenius G, Gabel M, et al: Infectious complications after multivisceral transplantation in adults. Transplant Proc 38:2683, 2006 19. Kimura T, Lauro A, Cescon M, et al: Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab. Clin Transplant 23:420, 2009 20. Cicalese L, Sileri P, Coady N, et al: Proposed protocol to reduce bacterial infectious complications in living related small bowel transplant recipients. Transplant Proc 34:950, 2002
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rejection and infection bigger problems than those observed with other solid organ transplantations.4,5 The immunosuppression protocols for IT and MVT must be strong to prevent acute cellular rejection (ACR), thus increasing the risk for infection, which is the main cause for
From the Faculdade de Ciências Médicas da Santa Casa de São Paulo (A.P.T., E.R.D., D.M.), and the GI Transplant Program, Hospital das Clinicas/FMUSP (A.I.D., R.P., L.A.C.D.), São Paulo, Brazil. Address reprint requests to André Ibrahim David, Rua Pamplona 1808, apto 52, Jardim Paulista, São Paulo, Brazil. E-mail: [email protected]
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.07.016
Transplantation Proceedings, 44, 2445–2448 (2012)
2445
2446
TREVIZOL, DAVID, DIAS ET AL
Table 1. Patient Survival Rate Presented According to Author and Immunosuppression Protocol Author (y)
N
Protocol
Patient Survival Rate %, 1/3/5 years
Nishida (2006) Nishida (2006) Zanfi (2010) Zanfi (2010) Lauro (2006) Lauro (2006) Kimura (2008) Kimura (2008) Yuan-Xin (2010) Vianna (2008)
39 37 12 28 12 17 11 23 5 27
1 2 1 2 1 2 1 2 2 3
57/48/nd 70/47/nd 78/76/66 79/6/43 92/82/nd 82/64/nd 80/80/75 90/70/60 nd 81/78/nd
Abbreviation: nd, no data.
death. Patient and graft survival rates have improved using induction therapy to reduce ACR early postoperatively as well as the need for high maintenance tacrolimus doses. However, infectious complications are still the leading factor in recipient deaths because of the strong immunosuppression.6 An adequate immunosuppression protocol must balance ACR and infection rates. We sought to analyze the reported results from leading transplantation centers over the last 5 years attempting to evaluate the current protocol that achieved the best overall results. MATERIALS AND METHODS This review was performed using PubMed focusing on immunosuppressive protocols for intestinal and multivisceral transplantation. Articles published from 2006 to 2010 were selected7–12 according to the criteria of information about the outcomes of immunosuppressive protocols. We compared three protocols: protocol 1; daclizumab (2 mg/kg/wk for 3 months and 1 mg/kg/wk for another 3 months) for induction plus maintenance treatment with tacrolimus (trough concentration ⫽ 15 to 20 ng/dL) and steroids; protocol 2; alemtuzumab (0.3 mg/kg in four doses on postoperative days 0, 1, 3, and 7) for induction and maintenance treatment with tacrolimus (8 to 12 ng/mL); and protocol 3: thymoglobulin (rATG; 10 mg/kg divided into five equivalent doses of 2 mg/kg, on postoperative days 0, 2, 4, and 6) plus rituximab (150 mg/m2 as a single dose on postoperative day 3) as induction treatment and maintenance with tacrolimus (12 to 15 ng/dL). We compared infection, ACR and patient survival rates.
and 3 year values were 62.23%, 56%, and 78% for protocols 1, 2, and 3, respectively (Fig 1). DISCUSSION
IT and MVT became possible with improved immunosuppression protocols, particularly in the induction protocols. While minimizing ACR the main cause of graft loss, demands high levels of immunosuppression, it can regulates extremely high incidences of bacterial infections with sepsis as the main cause of death.13 We compared three immunosuppressive protocols used in these settings: Protocol 1 included daclizumab as induction immunosuppression, protocol 2, alemtuzumab, the effect of which lasts approximately 6 month and protocol 3, rituximab plus thymoglobulin, which has possible protective effects against reperfusion injury when administered before organ reperfusion.14 –16 Protocol 2 showed the lowest ACR rate (34%), probably due to the stronger degree of induction treatment. Protocol 1 despite a high rate only showed mild cases of ACR, whereas 26.3% and 7.9% were moderate and severe, in protocol 2, respectively. Protocol 3 had the greatest number of severe ACRs episodes (47%). The infection rate was lower in protocol 2 (52%) than protocol 1 (62.5%). The 1-year survival rate was better using protocol 2 (79%) versus protocol 1 (70%). When comparing protocols 2 and 3, we observed that, although protocol 3 showed a higher ACR rate than protocol 2 (48% vs 34%), with almost half of them being severe (47%), only 30% of the episodes occurred in the first 90 days posttransplantation. MVT patients experienced only one severe ACR, possibly due to the protective effect of massive removal of native lymphoid tissue. Infection, the main cause of death, was significantly lower with protocol 3 (7.4%) than protocol 2 (62.5%). Tzakis et al17 described the most common infection sites to be the blood stream and respiratory tract, followed by the wound and intra-abdominal cavity. Half of the patients with bacteremia had it associated with the catheter site. Oltean et al18 reported that the central venous catheter (CVC) was Table 2. ACR and Infection Rates Presented According to Author and Immunosuppression Protocol
RESULTS
A total of 211 adults were transplanted. Protocol 1 included 74 patients; protocol 2, 105; and protocol 3, 27 (Tables 1 and 2). We found that protocol 2 showed the lowest rate of ACR (34%) in contrast to protocols 2 and 3 with 54% and 48% ACR rates, respectively. Protocol 1 patients developed only mild ACR, whereas those in protocols 2 and 3, moderate ACR in 26.3% and 11.7% of cases with severe ACR in 7.9% and 47% of cases of ACR, respectively. Infection rates were considerably lower in protocol 3 (7.4%). Protocols 1 and 2 showed infection rates of 62.5% and 52%, respectively. One-year patient survival rates were 70%, 78.76%, and 81%
Author (y)
Protocol
ACR Rate %/n Patients/n Mild/n Moderate/n Severe
Nishida (2006) Nishida (2006) Zanfi (2010) Zanfi (2010) Lauro (2006) Lauro (2006) Kimura (2008) Kimura (2008) Yuan-Xin (2010) Vianna (2008)
1 2 1 2 1 2 1 2 2 3
nd nd 66/8/9/—/— 42/12/11/3/— 42/5/6/—/— 12/2/—/2/— nd nd 60/3/7/3/1 48/13/9/2/8
Abbreviation: nd, no data.
Infection Rate %/n Patients
nd nd 66/8 57/16 58/7 53/9 nd nd 20/ 7,4/2
IMMUNOSUPPRESSION PROTOCOLS
2447
Fig 1. (A) Patient survival rate, (B) ACR rate, and (C) infection rate by immunosuppression protocol.
the leading location of infections followed by respiratory, intra-abdominal, and wound infections. However, neither study separated infections by immunosuppressive protocol or time after the procedure. In 2009, Kimura et al19 studied the main sites and pathogens related to infections in protocols 1 and 2. In the first month after transplant, the leading sites of bacterial infections were wound and intra-abdominal (ascites), followed by CVC venous catheter and blood stream. The main pathogens were Escherichia coli and Pseudomonas aeruginosa in protocol 1; and Enterococcus, Klebsiella, and Pseudomonas aeruginosa in protocol 2. After that, the main sites of bacterial infections were CVC and blood stream in both protocols, followed by broncho-alveolar lavage in protocol 1 and wound in protocol 2. Pseudomonas aeruginosa was the main pathogen of bacterial infections in protocol 1, whereas various pathogens were observed in protocol 2: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis, and others. In addition, protocol 2 seemed to be associated with a prolonged duration of first infection when compared with protocol 1, probably due to the stronger induction therapy. All but two deaths that
occured in both protocols were related to infectious complications, including sepsis and cytomegalovirus enteritis. Cicalese et al20 proposed the use of living related donors to reduce bacterial infections after IT. However, several risks including short bowel syndrome, small bowel obstruction, dysvitaminosis, and diarrhea should be considered when using living donors. Moreover, the most important issue is to provide an adequate length of intestine to the recipient to ensure enteral autonomy while preserving sufficient small bowel length in the donor. Infection is still a big problem in IT and MVT due to the immunosuppressive protocol. In conclusion, protocol 2 engendered the strongest immunosuppression based upon low ACR rates compared with the other regimens. But this strong immunosuppression resulted in an high rate of infection, which affected 1-year patient survival. Protocol 3 seemed to be the best available immunosuppression protocol, which balanced between ACR and infection rates. REFERENCES 1. Kirkman RL: Small bowel transplantation. Transplantation 37:429, 1984
2448 2. Starzl TE, Rowe MI, Todo S, et al: Transplantation of multiple abdominal viscera. JAMA 261:1449, 1989 3. Starzl TE, Todo S, Fung J, et al: FK 506 for human liver, kidney and pancreas transplantation. Lancet 2:1000, 1989 4. Abu-Elmagd K: The history of intestinal transplantation. In: Nakim NS, Papalois VE(eds): The History of Organ and Cell Transplantation. London: Imperial College Press; 2003, 171 5. Abu-Elmagd K, Reyes J, Bond G, et al: Clinical intestinal transplantation: a decade of experience at a single center. Ann Surg 234:404, 2001 6. Grant D, Abu-Elmagd K, Reyes J, et al: 2003 report of the intestine transplant registry: a new era has dawned. Ann Surg 241:607, 2005 7. Nishida S, Levi DM, Moon JI, et al: Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients. Transplant Proc 38:1747, 2006 8. Zanfi C, Lauro A, Cescon M, et al: Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceraltransplantation: rejection and infection rates in 40 recipients during the early postoperativeperiod. Transplant Proc 42:35, 2010 9. Lauro A, Amaduzzi A, Dazzi A, et al: Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceraltransplantation: a comparison of two different regimens on 29 recipients during the earlypost-operative period. Dig Liver Dis 39:253, 2007. Epub 2007 Feb 1 10. Kimura T, Lauro A, Cescon M, et al: Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab. Clin Transplant 23:420, 2009 11. Yuan-Xin L, Ning L, You-Sheng L, et al: Preliminary experience with alemtuzumab induction therapy combined with
TREVIZOL, DAVID, DIAS ET AL maintenancelow-dose tacrolimus monotherapy in small-bowel transplantation in China. Transplant Proc 42:29, 2010 12. Vianna RM, Mangus RS, Fridell JA, et al: Induction immunosuppression with thymoglobulin and rituximab in intestinal andmultivisceral transplantation. Transplantation 85:1290, 2008 13. Jordan SC, Pescovitz MD: Presensitization: the problem and its management. Clin J Am Soc Nephrol 1:421, 2006 14. Beiras-Fernandez A, Chappell D, Hammer C, et al: Influence of polyclonal anti-thymocyte globulins upon ischemiareperfusion injury in a non-human primate model. Transplant Immunol 15:273, 2006 15. Bogetti D, Jarzembowski TM, Sankary HN, et al: Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy. Transplant Proc 37:404, 2005 16. Bogetti D, Sankary HN, Jarzembowski TM, et al: Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury. Clin Transplant 19:507, 2005 17. Tzakis AG, Kato T, Levi DM, et al: 100 multivisceral transplants at a single center. Ann Surg 242:480, 2005 18. Oltean M, Herlenius G, Gabel M, et al: Infectious complications after multivisceral transplantation in adults. Transplant Proc 38:2683, 2006 19. Kimura T, Lauro A, Cescon M, et al: Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab. Clin Transplant 23:420, 2009 20. Cicalese L, Sileri P, Coady N, et al: Proposed protocol to reduce bacterial infectious complications in living related small bowel transplant recipients. Transplant Proc 34:950, 2002