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Liver transplantation across ABO blood groups in children
Liver Transplantation Across ABO Blood Groups in Children M. Szymczak, P. Kalicinski, A. Kaminski, H. Ismail, T. Drewniak, P. Nachulewicz, and D. Broniszczak ABSTRACT Late results after ABOI LTx are inferior to ABO compatible organs. We report seven patients who received LTx across ABO group for emergency indications. The blood type combinations were: A to O in three, B to O in two, and B to A in two. Episodes of acute and chronic rejection, immunosuppression, and biochemical and functional tests after transplantation as well as patient and graft survival were compared between ABOI group and patients with compatible ABO group transplanted due to FLF (group I) or in an elective setting (group II). Four children are alive. Two children died of sepsis and CNS damage or MOF, and one patient died during transplantation because of cardiac failure. All recipients of ABOI grafts received immunosuppression with cyclosporine or tacrolimus and steroids. MMF was added in two subjects, and induction with antilymphocyte globulins used in five patients. An acute rejection episode was diagnosed in two recipients between 7 and 11 days after LTx. All four living patients with ABOI grafts are doing well with follow-up time between 11 months and 5 years. In one patient PTLD occurred at 1 year after ABOI LTx but was cured by discontinuation of immunosuppression and administration of rituximab. Graft survival in the ABOI group was 57.1% versus 71% in group I and 73% in group II. Respective patients survival was 57.1% 71%, and 82.0% respectively. In conclusion, in urgent cases ABOI transplantation is justified in pediatric patients when compatible grafts are not available.
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IVER TRANSPLANTATION across ABO blood groups is associated with a high risk of severe early acute and late chronic rejection. Therefore crossing the ABO barrier in solid organ transplantation is usually not recommended unless the situation is urgent and a compatible graft is not immediately available. The late results after ABO incompatible (ABOI) liver transplantation are generally inferior to those after an ABO compatible (ABOC) graft.1 The purpose of this study was to report our singlecenter experience with pediatric liver transplantation across ABO groups.
PATIENTS AND METHODS Between 1990 and 2002, 156 liver transplantations (LTx) were performed in 144 children including seven (4.5%) ABOI grafts. All of these recipients presented with urgent indications for liver transplantation: fulminant liver failure (FLF) with coma (n ⫽ 6) and primary graft nonfunction (PNF) (n ⫽ 1). Age at transplantation ranged from 5 to 18 years. The blood type combinations were: A to O in three patients, B to O in two patients, and B to A in two patients. All recipients of ABOI grafts received immunosuppression with cyclosporine or tacrolimus and steroids, together with mycophenolate mofetil (MMF) in two patients. Antilymphocyte
globulins (ATG-2, daclizumab-2, basiliximab-1) were used as the induction therapy in five patients. Deterioration of biochemical parameters was the only indication for graft biopsy. The present analysis examined patient and graft survival, rejection rate, and early- and long-term biochemical tests. Patient and graft survival were compared between recipients of ABOI grafts (ABOI group) and those with compatible grafts transplanted due to fulminant hepatic failure or PNF (group I) and to all remaining elective patients who had received compatible grafts (group II).
RESULTS
Four children with ABOI grafts are alive with follow-up from 11 months to 5 years (mean 21 months) after LTx. In all survivors biochemical parameters of liver function are within normal range. Three patients died on post-Tx days 0, 7, and 272 due to cardiac arrest, sepsis, and CNS damage, and sepsis and From the Department of Pediatric Surgery and Organ Transplantation, Warsaw, Poland. Address reprint requests to M. Szymczak, Children’s Memorial Health Institute, Department of Pediatric Surgery, Al. Dzieci Polskich 20, Warsaw 04-736, Poland
© 2003 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/S0041-1345(03)00846-7
Transplantation Proceedings, 35, 2273–2274 (2003)
2273
2274
multiorgan failure, respectively. Neither hyperacute rejection nor hemolysis occurred in any ABOI recipient. Biopsyproven mild acute rejection episodes were diagnosed in two children on day 7 and day 11 after transplantation; they were successfully reversed with steroid boluses. The one patient who developed PTLD at 1 year after LTx, was successfully treated with anti-CD20 antibodies and discontinuation of immunosuppression for 6 months. Thereafter a mild rejection episode developed, which resolved upon reintroduction of low-dose tacrolimus. Actual patient survival is 57.1% in the ABOI group versus 71% in group I and 82.0% in group II and the graft survival 57.1%, 71%, and 73%, respectively. DISCUSSION
ABOI liver transplantation is questioned and even prohibited by some transplant organizations due to the high graft loss rate. A higher incidence of rejection as well as biliary and vascular complications have been reported to occur and be associated with reduced patient and graft survival.2– 4 Previous reports describe long-term patient survival rates in ABOI liver transplantation between 30% and 60% compared with about 80% for ABO compatible liver grafts.5,6 Patients with FLF or PNF after LTx will die, however, due to the lack of a compatible liver graft within a short time, while elective patients can wait much longer. In our series patients who received ABOI grafts were seriously ill with a poor prognosis for survival after trans-
SZYMCZAK, KALICINSKI, KAMINSKI ET AL
plantation (even with a compatible graft) that was much lower than that of elective patients. We were still able to achieve almost 60% long-term survival in this group, which compares favorably to the results in other groups of patients who are offered liver transplantation without question (eg, patients with primary liver tumors). Moreover, with the modern immunosuppressive protocols both acute and chronic rejection have not been a significant problem in our patients, even in the case of drug discontinuation due to PTLD. None of deaths among these recipients was directly related to ABO incompatibility, but rather to complications connected to the primary indication for LTx. Based on our experience in pediatric recipients with ABOI liver transplantation, we assume that in selected cases of emergent indications for liver transplantation (FLF, PNF, early graft vascular thrombosis), ABOI grafts should be offered to these patients, particularly in centers with low mortality, rates among elective patients. REFERENCES 1. Rydberg L: Transfus Med 11:325, 2001 2. Farges O, Nocci Kalil A, Samuel D, et al: Transplant Proc 27:1701, 1995 3. Lo CM, Shaked A, Busuttil RW: Transplantation 15:543–7, 1994 4. Farges O, Kalil AN, Samuel D, et al: Transplantation 27:1124, 1995 5. Renard TH, Andrews WS: Transplantation 53:116, 1992 6. Yandza T, Lambert T, Alverez F, et al: Transplantation 15:46, 1994
L
IVER TRANSPLANTATION across ABO blood groups is associated with a high risk of severe early acute and late chronic rejection. Therefore crossing the ABO barrier in solid organ transplantation is usually not recommended unless the situation is urgent and a compatible graft is not immediately available. The late results after ABO incompatible (ABOI) liver transplantation are generally inferior to those after an ABO compatible (ABOC) graft.1 The purpose of this study was to report our singlecenter experience with pediatric liver transplantation across ABO groups.
PATIENTS AND METHODS Between 1990 and 2002, 156 liver transplantations (LTx) were performed in 144 children including seven (4.5%) ABOI grafts. All of these recipients presented with urgent indications for liver transplantation: fulminant liver failure (FLF) with coma (n ⫽ 6) and primary graft nonfunction (PNF) (n ⫽ 1). Age at transplantation ranged from 5 to 18 years. The blood type combinations were: A to O in three patients, B to O in two patients, and B to A in two patients. All recipients of ABOI grafts received immunosuppression with cyclosporine or tacrolimus and steroids, together with mycophenolate mofetil (MMF) in two patients. Antilymphocyte
globulins (ATG-2, daclizumab-2, basiliximab-1) were used as the induction therapy in five patients. Deterioration of biochemical parameters was the only indication for graft biopsy. The present analysis examined patient and graft survival, rejection rate, and early- and long-term biochemical tests. Patient and graft survival were compared between recipients of ABOI grafts (ABOI group) and those with compatible grafts transplanted due to fulminant hepatic failure or PNF (group I) and to all remaining elective patients who had received compatible grafts (group II).
RESULTS
Four children with ABOI grafts are alive with follow-up from 11 months to 5 years (mean 21 months) after LTx. In all survivors biochemical parameters of liver function are within normal range. Three patients died on post-Tx days 0, 7, and 272 due to cardiac arrest, sepsis, and CNS damage, and sepsis and From the Department of Pediatric Surgery and Organ Transplantation, Warsaw, Poland. Address reprint requests to M. Szymczak, Children’s Memorial Health Institute, Department of Pediatric Surgery, Al. Dzieci Polskich 20, Warsaw 04-736, Poland
© 2003 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/S0041-1345(03)00846-7
Transplantation Proceedings, 35, 2273–2274 (2003)
2273
2274
multiorgan failure, respectively. Neither hyperacute rejection nor hemolysis occurred in any ABOI recipient. Biopsyproven mild acute rejection episodes were diagnosed in two children on day 7 and day 11 after transplantation; they were successfully reversed with steroid boluses. The one patient who developed PTLD at 1 year after LTx, was successfully treated with anti-CD20 antibodies and discontinuation of immunosuppression for 6 months. Thereafter a mild rejection episode developed, which resolved upon reintroduction of low-dose tacrolimus. Actual patient survival is 57.1% in the ABOI group versus 71% in group I and 82.0% in group II and the graft survival 57.1%, 71%, and 73%, respectively. DISCUSSION
ABOI liver transplantation is questioned and even prohibited by some transplant organizations due to the high graft loss rate. A higher incidence of rejection as well as biliary and vascular complications have been reported to occur and be associated with reduced patient and graft survival.2– 4 Previous reports describe long-term patient survival rates in ABOI liver transplantation between 30% and 60% compared with about 80% for ABO compatible liver grafts.5,6 Patients with FLF or PNF after LTx will die, however, due to the lack of a compatible liver graft within a short time, while elective patients can wait much longer. In our series patients who received ABOI grafts were seriously ill with a poor prognosis for survival after trans-
SZYMCZAK, KALICINSKI, KAMINSKI ET AL
plantation (even with a compatible graft) that was much lower than that of elective patients. We were still able to achieve almost 60% long-term survival in this group, which compares favorably to the results in other groups of patients who are offered liver transplantation without question (eg, patients with primary liver tumors). Moreover, with the modern immunosuppressive protocols both acute and chronic rejection have not been a significant problem in our patients, even in the case of drug discontinuation due to PTLD. None of deaths among these recipients was directly related to ABO incompatibility, but rather to complications connected to the primary indication for LTx. Based on our experience in pediatric recipients with ABOI liver transplantation, we assume that in selected cases of emergent indications for liver transplantation (FLF, PNF, early graft vascular thrombosis), ABOI grafts should be offered to these patients, particularly in centers with low mortality, rates among elective patients. REFERENCES 1. Rydberg L: Transfus Med 11:325, 2001 2. Farges O, Nocci Kalil A, Samuel D, et al: Transplant Proc 27:1701, 1995 3. Lo CM, Shaked A, Busuttil RW: Transplantation 15:543–7, 1994 4. Farges O, Kalil AN, Samuel D, et al: Transplantation 27:1124, 1995 5. Renard TH, Andrews WS: Transplantation 53:116, 1992 6. Yandza T, Lambert T, Alverez F, et al: Transplantation 15:46, 1994