- Email: [email protected]
Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies
Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies R. Parekhc, M. Kazimia, S. Skorupskib, O. Fagoagab, S. Jafric, and M.C. Segoviac,* From the Departments of aTransplant Surgery, bPathology, and cGastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan
ABSTRACT Background. We describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. Patients and Methods. We used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. Results. Four patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. Conclusions. We report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.
I
SOLATED intestine (small bowel) transplantation (IT) and multivisceral organ transplantation (MVT) have been associated with high risk of allo-immunity. The intestinal allograft is highly vascularized and has a large number of donor epithelial and lymphoid cells; hence it is highly immunogenic. Humoral immunity plays a big role in allograft dysfunction and acute or chronic rejection after intestinal transplantation [1e4]. Preformed and de novo donor-specific antibodies (DSA) are associated with poor outcomes in patients undergoing intestinal transplantation, with higher rates of rejection and allograft dysfunction [5e9]. At our institution, a standard immunosuppression protocol has been implemented for patients undergoing IT and ª 2016 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 48, 489e491 (2016)
MVT. We designed a modified protocol for patients undergoing IT and MVT across a positive crossmatch with evidence of class I and/or class II DSA. Patients with evidence of DSA who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events, and were compared to the procedure-matched control patients without positive DSA who were given the standard protocol of immunosuppression. *Address correspondence to Maria Cristina Segovia, MD, Senior Staff Physician, Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI 48202. Tel: (313) 916-8632; Fax: (313) 916-5960. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.10.084
489
490
PAREKH, KAZIMI, SKORUPSKI ET AL Table 1. Patients Who Underwent Transplantation Across Positive Crossmatch
Patient No.
1 2 3 4
(MVT) (IT) (MVT) (IT)
Major Infection
Minor Infection
Major Rejection
Minor Rejection
NO NO YES (pneumonia, empyema) NO
YES (peritonitis) YES (bacteremia) NO YES (Urinary tract infection)
NO NO YES NO
NO NO NO NO
Abbreviations: MTV, multivisceral transplantation; IT, intestine transplantation.
PATIENTS AND METHODS
DISCUSSION
Four patients underwent intestinal transplantation within a single year in 2013 across a positive T- and B-cell flow crossmatch. They were compared with procedure-matched controls with negative final crossmatch. The standard protocol for immunosuppression consists of tacrolimus at goal trough level of 15 to 20 ng/dL, methylprednisolone taper starting at 500 mg intravenously, anti-thymocyte globulin at 2 mg/kg on postoperative days (POD) 0, 2, and 4, and basiliximab 20 mg intravenously monthly for 6 months beginning on POD 14. The patients with positive prospective and retrospective crossmatch were given rituximab 150 mg/m2 beginning 4 hours preoperatively and intravenous immunoglobulin (IVIG) 1 g/kg preoperatively in addition to the standard protocol. DSA levels were checked at monthly intervals. All patients were screened for rejection by endoscopic evaluation and biopsy of the small intestine on a routine basis. All patients were followed up for 12 months, and episodes of rejection and infection were documented. Infections were categorized as major and minor. Major infections were defined as those presenting as severe sepsis, septic shock, or fungal infections. Cytomegalovirus (CMV) infections were also noted after the transplantation.
The small intestine has a large proportion of lymphoid tissue in the form of Peyer’s patches and lymph nodes, making it highly immunogenic. It also has abundant commensal bacterial flora. Hence, intestinal transplant patients are prone to rejection and susceptible to infections [1e4]. Based on the 2011 Intestinal Transplant Registry report of 2011, 42.6% patients experienced rejection within the first 12 months of transplantation [10]. This has been shown to cause a high rate of graft failure in intestinal transplant patients. Antibody-mediated rejection usually does not respond to conventional anti-rejection therapy, which is mainly directed at T-cellemediated processes. Preformed and de novo DSA are associated with higher rates of rejection and graft failure. Previous studies have shown that IVIG-based immunosuppression protocols have reduced the levels of DSA and have resulted in better outcomes in presensitized patients undergoing intestinal transplantation. IVIG has been shown to inhibit residual antibodies in patients with antibody-mediated rejection. Other therapies used for antibody-mediated rejection are rituximab, which depletes the B cells; plamaspheresis, which eliminates the circulating antibodies; and bortezomib, a proteasome inhibitor that has been shown to be effective in decreasing DSA levels by depleting the plasma cells [6,7,11e13]. At our institution, we use a modified protocol for immunosuppression for intestinal transplantation with positive DSA (preformed or de novo). In addition to the conventional immunosuppression, patients are given Rituximab and IVIG to decrease the risk of antibody-mediated rejection. Using our modified protocol, only 1 of the 4 patients who underwent transplantation across a positive crossmatch experienced acute rejection within the first 12 months of transplantation. Preformed DSA titers were significantly decreased in 3 patients using the modified protocol; however, the risk of infection was higher among these patients
RESULTS
Among the patients with positive crossmatch, 1 patient had an episode of major acute cellular rejection 10 months after IT (Table 1). This was treated with increased immunosuppression including rituximab, anti-thymocyte globulin, and adalimumab, with complete resolution. CMV infection was not seen in any patient with positive crossmatch. A major bacterial infection was seen in 1 patient, and minor bacterial infections were seen in the other 3 patients (Table 1). Three patients had a significant decrease in their pre-existing DSA titers using the modified protocol for immunosuppression. One patient had a rise in the DSA titers at 7 months posttransplantation. The patient was given additional basiliximab on a monthly basis for 6 months and subsequently had a reduction of DSA titers (Table 3). Among the procedure-matched controls with negative final crossmatch who received standard immunosuppression protocol (without preoperative rituximab or intravenous immunoglobulin), 2 patients had evidence of mild acute cellular rejection (Table 2). One patient was found to have CMV viremia along with invasion to the colonic mucosa requiring prolonged treatment with ganciclovir. Two patients developed minor infections. No major infections were seen (Table 2).
Table 2. Patients Who Underwent Transplantation Across Negative Crossmatch Major Patient No. Infection
1 2 3 4
(MVT) (IT) (MVT) (IT)
NO NO NO NO
Minor Infection
NO NO YES (wound infection) YES (Urinary tract infection)
Major Minor Rejection Rejection
NO NO NO NO
YES NO NO YES
Abbreviations: MTV, multivisceral transplantation; IT, intestine transplantation.
INTESTINE TRANSPLANTATION AND DSA
491
Table 3. Donor-Specific Antibody (DSA) Values for Transplantation Across Positive Crossmatch Patient No.
Donor Antigens
DSA at Day 0
Patient 1 A(3,30) B(7,42) Bw6 Cw(15,17) DR(8,18) DR52 DQ(4,-) DQA(4,-) Patient 2 A(3,30) B(35,55) C(9,4) DR(1,14) DR52 DQA(1,-) DQ(5,-)
A(2,24) B(51,57) Bw4 Cw(6,15) DR(4,7) DR 53 DQB(8,9)
A24: 5804 B51: 8103 DQ8: 23221 DQ9: 21717
Patient 3 A(1,2) B(27,44) Bw4 C(1,5) DR(1,4) DR53 DQA(1,3) DQ(7,5) Patient 4 A(3,25) B(18,65) Bw6 Cw(8,12) DR(7,7) DR53 DQ(2,-) DQA(2,-)
A(1,2) B(8,-) Bw6 Cw(7,-) DR(17,-) DR52 DQB(2,-)
A(1,11) B(7,35) Bw6 Cw(7,4) DR(4,12) DR52 DR53 DQB(7,7) A(30,33) B(42,53) Bw(4,6) Cw(4,17) DR(11,18) DRw(52) DQB(4,6)
DSA at Day 30
DSA at Day 60
A24: <1000 B51: <1000 DQ8: <1000 DQ9: 11152
A24: <1000 B51: <1000 DQ8: <1000 DQ9: 8002
A24: <1000 B51: <1000 DQ8: <1000 DQ9: <1000
A24: <1000 B51: <1000 DQ8: <1000 DQ9: <1000
A1: 20122 A2 <1000 B8: <1000 C7: 13977 DQ2: 26769 B35: 11053 DR12: 15114
A1: <1000 A2: 7137 B8: 2993 C7: <1000 DQ2: <1000
A1: <1000 A2: 6270 B8: 2285 C7: <1000 DQ2: <1000
A1: <1000 A2: 7096 B8: 3243 C7: <1000 DQ2: <1000
A1: <1000 A2: 4097 B8: 2176 C7: <1000 DQ2: <1000
NOT TESTED
NOT TESTED
NOT TESTED
B35: <1000 DR12: 3677
DQ6: 16876 DR11: 4713
DQ6: 4919 DR11: <1000
DQ6: <1000 DR11: <1000
DQ6: <1000 DR11: <1000
DQ6: <1000 DR11: <1000
compared to the patients with negative crossmatch. Higher infection rates can be explained by more intensive immunosuppressive regimens. Kubal et al showed that there was no difference in acute rejection and allograft dysfunction in patients with positive and negative crossmatch undergoing intestinal transplant with liver-free allografts using an intense induction regimen with anti-thymocyte globulin, rituximab and interleukin-2 receptor antibody [14]. Our study shows that IT and MVT, across a positive crossmatch, have good outcomes with a low rate of rejection using a modified immunosuppression protocol with rituximab and IVIG in addition to standard immunosuppression; however, this was associated with potentially higher rates of major infections compared to those in patients with negative crossmatch. REFERENCES [1] Farmer DG, Venick RS, Colangelo J, Esmailian Y, Yersiz H, Duffy JP, et al. Pretransplant predictors of survival after intestinal transplantation: analysis of a single-center experience of more than 100 transplants. Transplantation 2010;90:1574e80. [2] Mazariegos GV, Steffick DE, Horslen S, Farmer D, Fryer J, Grant D, et al. Intestine transplantation in the United States, 1999e2008. Am J Transplant 2010;10:1020e34. [3] Fishbein TM. Intestinal transplantation. N Engl J Med 2009;361:998e1008. [4] Takemoto SK, Zeevi A, Feng S, Colvin RB, Jordan S, Kobashigawa J, et al. National conference to assess antibodymediated rejection in solid organ transplantation. Am J Transplant 2004;4:1033e41. [5] Kaneku H, O’Leary JG, Banuelos N, Jennings LW, Susskind BM, Klintmalm GB, et al. De novo donor-specific HLA
DSA at Day 180
DSA at 1 Year
antibodies decrease patient and graft survival in liver transplant recipients. Am J Transplant 2013;13:1541e8. [6] Kaneku H, Wozniak LJ. Donor-specific human leukocyte antigen antibodies in intestinal transplantation. Curr Opin Organ Transplant 2014;19:261e6. [7] Gerlach UA, Lachmann N, Sawitzki B, et al. Clinical relevance of the de novo production of anti-HLA antibodies following intestinal and multivisceral transplantation. Transplant Int 2014;27: 280e9. [8] Bond G, Reyes J, Mazariegos G, Wu T, Schaefer N, Demetris J, et al. The impact of positive T-cell lymphocytotoxic crossmatch on intestinal allograft rejection and survival. Transplant Proc 2000;32:1197e8. [9] Abu-Elmagd KM, Wu G, Costa G, Lunz J, Martin L, Koritsky DA, et al. Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant 2012;12:3047e60. [10] Smith JM, Skeans MA, Thompson B, Horslen SP, Edwards EB, Harper AM, et al. OPTN/SRTR 2011 Annual Data Report: intestine. Am J Transplant 2013;13(Suppl 1):103e18. [11] Gerlach UA, Schoenemann C, Lachmann N, et al. Salvage therapy for refractory rejection and persistence of donor-specific antibodies after intestinal transplantation using the proteasome inhibitor bortezomib. Transplant Int 2011;24:43e5. [12] Tsai HL, Island ER, Chang JW, Gonzalez-Pinto I, Tryphonopoulos P, Nishida S, et al. Association between donorspecific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation. Transplantation 2011;92: 709e15. [13] Hawksworth JS, Rosen-Bronson S, Island E, Girlanda R, Guerra JF, Valdiconza C, et al. Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching. Am J Transplant 2012;12(Suppl 4):S33e42. [14] Kubal CA, Mangus RS, Vianna RM, Lobashevsky A, Mujtaba MA, Higgins N, et al. Impact of positive flow cytometry crossmatch on outcomes of intestinal/multivisceral transplantation: role anti-IL-2 receptor antibody. Transplantation 2013;95:1160e6.
ABSTRACT Background. We describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. Patients and Methods. We used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. Results. Four patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. Conclusions. We report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.
I
SOLATED intestine (small bowel) transplantation (IT) and multivisceral organ transplantation (MVT) have been associated with high risk of allo-immunity. The intestinal allograft is highly vascularized and has a large number of donor epithelial and lymphoid cells; hence it is highly immunogenic. Humoral immunity plays a big role in allograft dysfunction and acute or chronic rejection after intestinal transplantation [1e4]. Preformed and de novo donor-specific antibodies (DSA) are associated with poor outcomes in patients undergoing intestinal transplantation, with higher rates of rejection and allograft dysfunction [5e9]. At our institution, a standard immunosuppression protocol has been implemented for patients undergoing IT and ª 2016 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 48, 489e491 (2016)
MVT. We designed a modified protocol for patients undergoing IT and MVT across a positive crossmatch with evidence of class I and/or class II DSA. Patients with evidence of DSA who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events, and were compared to the procedure-matched control patients without positive DSA who were given the standard protocol of immunosuppression. *Address correspondence to Maria Cristina Segovia, MD, Senior Staff Physician, Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI 48202. Tel: (313) 916-8632; Fax: (313) 916-5960. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.10.084
489
490
PAREKH, KAZIMI, SKORUPSKI ET AL Table 1. Patients Who Underwent Transplantation Across Positive Crossmatch
Patient No.
1 2 3 4
(MVT) (IT) (MVT) (IT)
Major Infection
Minor Infection
Major Rejection
Minor Rejection
NO NO YES (pneumonia, empyema) NO
YES (peritonitis) YES (bacteremia) NO YES (Urinary tract infection)
NO NO YES NO
NO NO NO NO
Abbreviations: MTV, multivisceral transplantation; IT, intestine transplantation.
PATIENTS AND METHODS
DISCUSSION
Four patients underwent intestinal transplantation within a single year in 2013 across a positive T- and B-cell flow crossmatch. They were compared with procedure-matched controls with negative final crossmatch. The standard protocol for immunosuppression consists of tacrolimus at goal trough level of 15 to 20 ng/dL, methylprednisolone taper starting at 500 mg intravenously, anti-thymocyte globulin at 2 mg/kg on postoperative days (POD) 0, 2, and 4, and basiliximab 20 mg intravenously monthly for 6 months beginning on POD 14. The patients with positive prospective and retrospective crossmatch were given rituximab 150 mg/m2 beginning 4 hours preoperatively and intravenous immunoglobulin (IVIG) 1 g/kg preoperatively in addition to the standard protocol. DSA levels were checked at monthly intervals. All patients were screened for rejection by endoscopic evaluation and biopsy of the small intestine on a routine basis. All patients were followed up for 12 months, and episodes of rejection and infection were documented. Infections were categorized as major and minor. Major infections were defined as those presenting as severe sepsis, septic shock, or fungal infections. Cytomegalovirus (CMV) infections were also noted after the transplantation.
The small intestine has a large proportion of lymphoid tissue in the form of Peyer’s patches and lymph nodes, making it highly immunogenic. It also has abundant commensal bacterial flora. Hence, intestinal transplant patients are prone to rejection and susceptible to infections [1e4]. Based on the 2011 Intestinal Transplant Registry report of 2011, 42.6% patients experienced rejection within the first 12 months of transplantation [10]. This has been shown to cause a high rate of graft failure in intestinal transplant patients. Antibody-mediated rejection usually does not respond to conventional anti-rejection therapy, which is mainly directed at T-cellemediated processes. Preformed and de novo DSA are associated with higher rates of rejection and graft failure. Previous studies have shown that IVIG-based immunosuppression protocols have reduced the levels of DSA and have resulted in better outcomes in presensitized patients undergoing intestinal transplantation. IVIG has been shown to inhibit residual antibodies in patients with antibody-mediated rejection. Other therapies used for antibody-mediated rejection are rituximab, which depletes the B cells; plamaspheresis, which eliminates the circulating antibodies; and bortezomib, a proteasome inhibitor that has been shown to be effective in decreasing DSA levels by depleting the plasma cells [6,7,11e13]. At our institution, we use a modified protocol for immunosuppression for intestinal transplantation with positive DSA (preformed or de novo). In addition to the conventional immunosuppression, patients are given Rituximab and IVIG to decrease the risk of antibody-mediated rejection. Using our modified protocol, only 1 of the 4 patients who underwent transplantation across a positive crossmatch experienced acute rejection within the first 12 months of transplantation. Preformed DSA titers were significantly decreased in 3 patients using the modified protocol; however, the risk of infection was higher among these patients
RESULTS
Among the patients with positive crossmatch, 1 patient had an episode of major acute cellular rejection 10 months after IT (Table 1). This was treated with increased immunosuppression including rituximab, anti-thymocyte globulin, and adalimumab, with complete resolution. CMV infection was not seen in any patient with positive crossmatch. A major bacterial infection was seen in 1 patient, and minor bacterial infections were seen in the other 3 patients (Table 1). Three patients had a significant decrease in their pre-existing DSA titers using the modified protocol for immunosuppression. One patient had a rise in the DSA titers at 7 months posttransplantation. The patient was given additional basiliximab on a monthly basis for 6 months and subsequently had a reduction of DSA titers (Table 3). Among the procedure-matched controls with negative final crossmatch who received standard immunosuppression protocol (without preoperative rituximab or intravenous immunoglobulin), 2 patients had evidence of mild acute cellular rejection (Table 2). One patient was found to have CMV viremia along with invasion to the colonic mucosa requiring prolonged treatment with ganciclovir. Two patients developed minor infections. No major infections were seen (Table 2).
Table 2. Patients Who Underwent Transplantation Across Negative Crossmatch Major Patient No. Infection
1 2 3 4
(MVT) (IT) (MVT) (IT)
NO NO NO NO
Minor Infection
NO NO YES (wound infection) YES (Urinary tract infection)
Major Minor Rejection Rejection
NO NO NO NO
YES NO NO YES
Abbreviations: MTV, multivisceral transplantation; IT, intestine transplantation.
INTESTINE TRANSPLANTATION AND DSA
491
Table 3. Donor-Specific Antibody (DSA) Values for Transplantation Across Positive Crossmatch Patient No.
Donor Antigens
DSA at Day 0
Patient 1 A(3,30) B(7,42) Bw6 Cw(15,17) DR(8,18) DR52 DQ(4,-) DQA(4,-) Patient 2 A(3,30) B(35,55) C(9,4) DR(1,14) DR52 DQA(1,-) DQ(5,-)
A(2,24) B(51,57) Bw4 Cw(6,15) DR(4,7) DR 53 DQB(8,9)
A24: 5804 B51: 8103 DQ8: 23221 DQ9: 21717
Patient 3 A(1,2) B(27,44) Bw4 C(1,5) DR(1,4) DR53 DQA(1,3) DQ(7,5) Patient 4 A(3,25) B(18,65) Bw6 Cw(8,12) DR(7,7) DR53 DQ(2,-) DQA(2,-)
A(1,2) B(8,-) Bw6 Cw(7,-) DR(17,-) DR52 DQB(2,-)
A(1,11) B(7,35) Bw6 Cw(7,4) DR(4,12) DR52 DR53 DQB(7,7) A(30,33) B(42,53) Bw(4,6) Cw(4,17) DR(11,18) DRw(52) DQB(4,6)
DSA at Day 30
DSA at Day 60
A24: <1000 B51: <1000 DQ8: <1000 DQ9: 11152
A24: <1000 B51: <1000 DQ8: <1000 DQ9: 8002
A24: <1000 B51: <1000 DQ8: <1000 DQ9: <1000
A24: <1000 B51: <1000 DQ8: <1000 DQ9: <1000
A1: 20122 A2 <1000 B8: <1000 C7: 13977 DQ2: 26769 B35: 11053 DR12: 15114
A1: <1000 A2: 7137 B8: 2993 C7: <1000 DQ2: <1000
A1: <1000 A2: 6270 B8: 2285 C7: <1000 DQ2: <1000
A1: <1000 A2: 7096 B8: 3243 C7: <1000 DQ2: <1000
A1: <1000 A2: 4097 B8: 2176 C7: <1000 DQ2: <1000
NOT TESTED
NOT TESTED
NOT TESTED
B35: <1000 DR12: 3677
DQ6: 16876 DR11: 4713
DQ6: 4919 DR11: <1000
DQ6: <1000 DR11: <1000
DQ6: <1000 DR11: <1000
DQ6: <1000 DR11: <1000
compared to the patients with negative crossmatch. Higher infection rates can be explained by more intensive immunosuppressive regimens. Kubal et al showed that there was no difference in acute rejection and allograft dysfunction in patients with positive and negative crossmatch undergoing intestinal transplant with liver-free allografts using an intense induction regimen with anti-thymocyte globulin, rituximab and interleukin-2 receptor antibody [14]. Our study shows that IT and MVT, across a positive crossmatch, have good outcomes with a low rate of rejection using a modified immunosuppression protocol with rituximab and IVIG in addition to standard immunosuppression; however, this was associated with potentially higher rates of major infections compared to those in patients with negative crossmatch. REFERENCES [1] Farmer DG, Venick RS, Colangelo J, Esmailian Y, Yersiz H, Duffy JP, et al. Pretransplant predictors of survival after intestinal transplantation: analysis of a single-center experience of more than 100 transplants. Transplantation 2010;90:1574e80. [2] Mazariegos GV, Steffick DE, Horslen S, Farmer D, Fryer J, Grant D, et al. Intestine transplantation in the United States, 1999e2008. Am J Transplant 2010;10:1020e34. [3] Fishbein TM. Intestinal transplantation. N Engl J Med 2009;361:998e1008. [4] Takemoto SK, Zeevi A, Feng S, Colvin RB, Jordan S, Kobashigawa J, et al. National conference to assess antibodymediated rejection in solid organ transplantation. Am J Transplant 2004;4:1033e41. [5] Kaneku H, O’Leary JG, Banuelos N, Jennings LW, Susskind BM, Klintmalm GB, et al. De novo donor-specific HLA
DSA at Day 180
DSA at 1 Year
antibodies decrease patient and graft survival in liver transplant recipients. Am J Transplant 2013;13:1541e8. [6] Kaneku H, Wozniak LJ. Donor-specific human leukocyte antigen antibodies in intestinal transplantation. Curr Opin Organ Transplant 2014;19:261e6. [7] Gerlach UA, Lachmann N, Sawitzki B, et al. Clinical relevance of the de novo production of anti-HLA antibodies following intestinal and multivisceral transplantation. Transplant Int 2014;27: 280e9. [8] Bond G, Reyes J, Mazariegos G, Wu T, Schaefer N, Demetris J, et al. The impact of positive T-cell lymphocytotoxic crossmatch on intestinal allograft rejection and survival. Transplant Proc 2000;32:1197e8. [9] Abu-Elmagd KM, Wu G, Costa G, Lunz J, Martin L, Koritsky DA, et al. Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant 2012;12:3047e60. [10] Smith JM, Skeans MA, Thompson B, Horslen SP, Edwards EB, Harper AM, et al. OPTN/SRTR 2011 Annual Data Report: intestine. Am J Transplant 2013;13(Suppl 1):103e18. [11] Gerlach UA, Schoenemann C, Lachmann N, et al. Salvage therapy for refractory rejection and persistence of donor-specific antibodies after intestinal transplantation using the proteasome inhibitor bortezomib. Transplant Int 2011;24:43e5. [12] Tsai HL, Island ER, Chang JW, Gonzalez-Pinto I, Tryphonopoulos P, Nishida S, et al. Association between donorspecific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation. Transplantation 2011;92: 709e15. [13] Hawksworth JS, Rosen-Bronson S, Island E, Girlanda R, Guerra JF, Valdiconza C, et al. Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching. Am J Transplant 2012;12(Suppl 4):S33e42. [14] Kubal CA, Mangus RS, Vianna RM, Lobashevsky A, Mujtaba MA, Higgins N, et al. Impact of positive flow cytometry crossmatch on outcomes of intestinal/multivisceral transplantation: role anti-IL-2 receptor antibody. Transplantation 2013;95:1160e6.