ABO-incompatible adult living donor liver transplantation for hepatocellular carcinoma

Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the need for pretransplantation treatment may be eliminated, which may reduce overall morbidity. In this article, we have described 8 adult HCC patients who successfully underwent LDLT from ABO-incompatible donors. Antirejection therapy included multiple preoperative plasmaphereses, splenectomy, and an immunosuppressive regimen with tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of the ABO-identical cases. In addition, we also performed intrahepatic arterial infusion of prostaglandin E1. In 5 patients, we administered a single dose of rituximab, a chimeric CD20 monoclonal antibody. As a result of this treatment, 6/8 patients are still alive. Our experience has shown that it is possible to control antibody-mediated humoral rejection and other complications in adult ABO-incompatible LDLT.     

Successful case of adult ABO-incompatible liver transplantation: beneficial effects of intrahepatic artery infusion therapy: a case report

BACKGROUND: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However, <30% are cases involving adults. The difficultly of ABO-incompatible liver transplantation is associated with the high frequency of humoral rejection and local disseminated intravascular coagulation (DIC), leading to many postoperative complications. We report a successful case of adult ABO-incompatible liver transplantation with the use of an intrahepatic artery infusion. METHODS: A 36-year-old man with Wilson disease, underwent living donor liver transplantation from an ABO-incompatible donor. The immunosuppressive therapy included multiple perioperative plasmaphereses, splenectomy, and treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and blood level of tacrolimus were the same as in ABO-compatible cases. In addition to these therapies, we administered an intrahepatic arterial infusion with prostaglandin (PG) E1 alone. RESULTS: After perioperative plasmapheresis and cyclophosphamide, antidonor blood group antibody titers remained undiluted and without vascular complications throughout the postoperative course, but there was a tendency for bleeding that continued for 10 days after transplantation. On postoperative day 10, a reexploration was performed for intraabdominal bleeding. During another operation on postoperative day 59 a biloma was found and drained. The patient has now survived for 120 days after transplantation with normal liver function. CONCLUSIONS: Beneficial effect of intrahepatic artery infusion with PGE1 seems to be useful in adult ABO-incompatible liver transplantation.     

Intraportal infusion therapy as a novel approach to adult ABO-incompatible liver transplantation

BACKGROUND: ABO-incompatible liver transplantation is associated with an extremely complicated postoperative course, especially when the recipients are adults. METHODS: Two adult patients underwent living-donor liver transplantation from ABO-incompatible donors. The antirejection therapy included multiple perioperative plasmapheresis, splenectomy, systemic triple immunosuppressive regimen with tacrolimus, methylprednisolone, and cyclophophamide, or azathioprine. In addition to these conventional approaches, we performed intraportal infusion therapy after transplantation with methylprednisolone, prostaglandin E1, and gabexate mesilate. RESULTS: With our protocol, antidonor blood group antibody titers in both cases remained low without any evidence of rejection or vascular complications throughout the postoperative course. Biliary complications were transient and resolved completely. The patients have now survived 30 and 12 months posttransplantation and have regained normal life activity with good liver function. CONCLUSIONS: Our experience has shown the feasibility of controlling rejection and other complications in adult ABO-incompatible liver transplantation under intraportal infusion therapy.     

Adult living-donor liver transplantation with ABO-incompatible grafts

BACKGROUND: Liver transplantation using ABO-incompatible grafts is rarely performed because the reported outcome is poorer than with compatible grafts. We report our positive experience with adult-to-adult living-donor liver transplant (LDLT) using ABO-incompatible grafts. METHODS: The immunosuppressive protocol consisted of plasmapheresis/intravenous immunoglobulin infusion before LDLT followed by thymoglobulin induction and splenectomy, maintenance with tacrolimus/cyclosporine (FK/CSA), mycophenolate mofetil, and a rapid steroid taper. Plasmapheresis was planned for up to 3 months after LDLT aiming at maintaining the anti-ABO titers level below 1:16. Liver biopsies were routinely stained for humoral rejection with complement 4d (C4d) and for biliary damage with cytokeratin 7. RESULTS: Between January 2003 and September 2004, five patients, mean age 59 years, received an ABO-incompatible LDLT. Patient and graft survival was 80% at mean follow-up of 43 months (range, 34-54) for the four surviving patients. One patient died 4 months after LDLT. Humoral rejection occurred in one patient whereas acute cellular rejection was diagnosed in four patients. CONCLUSIONS: ABO-incompatible LDLT can be performed with patient and graft survival similar to compatible LDLT. Minimization of immunosuppression is possible, and chronic biliary damage is not the norm. Better tools than complement 4d staining must be researched to diagnose the features of immunologic damage to the graft. If these results will be confirmed in a greater number of patients, ABO-incompatible LDLT may be proposed when ABO-compatible donors are not available or when the ABO-incompatible donor is the better candidate.     

Adult ABO-incompatible liver transplantation by intraportal transfusion of donor-specific antigen: a case report

A 55-year-old-woman suffering from fluminant hepatitis owing to autoimmune hepatitis underwent ABO-incompatible liver transplantation (LRLD) of blood type A to B. In this study, we investigated whether a new immunosuppressive strategy by intraportal transfusion of donor-specific leukocytes (DSLT) separated from whole blood would yield immunological benefit in adult ABO-LRLD. The operative course was uneventful; she was discharged at 46 days postoperatively without humoral or cellular rejection. On immunologic analysis, 54.6% intrahepatic macrochimerism of donor type CD56+ T cells was recognized at 1 month after transplantation. The interleukin-10 Th2 cytokine level was increased on postoperative day 1. Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with our strategy of immunosuppression by intraportal administration of DSLT. Donor type CD56+ NKT cells may induce tolerance by a veto mechanism and/or an anti-idiotype network. ABO-incompatible liver transplantation may be improved by this strategy.     

A Comparison of splenectomy versus intensive posttransplant antidonor blood group antibody monitoring without splenectomy in ABO-incompatible kidney transplantation

BACKGROUND: Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. METHODS: We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). RESULTS: Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. CONCLUSIONS: Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.     

Impact of Intraportal Donor-Specific Leukocyte Transfusion for Adult ABO-Incompatible Liver Transplantation

Introduction

We have reported that repeated donor-specific leukocyte transfusions (DSLT) via the portal vein allow rapid reduction of immunosuppressants and decrease the occurrence of acute cellular rejection. Herein, we examined the immunological benefits of DSLT in adult ABO-incompatible living donor liver transplantation (LDLT).

Materials and Methods

Ten adult patients (MELD score, 19.4 ± 7.3; range, 12-29) underwent LDLT from ABO-incompatible donors from August 2003 to November 2007. The antirejection therapy included multiple perioperative plasmaphereses, splenectomy, and quadruple immunosuppression. In addition to these conventional approaches, we performed 4 intraportal administrations of DSLT after transplantation.

Results

There was no humoral rejection in any patient. Two patients experienced mild cellular rejection requiring steroid pulse therapy. Both donor-specific immunoglobulin (Ig)M and IgG A/B antibodies in all patients decreased following transplantation by 16 fold. By flow cytometry, donor type of CD56+NK T cells existed in the liver graft showing macrochimerism at 1 month after liver transplantation. Furthermore, interleukin (IL)-10 production of Th2 type cytokines was up-regulated after transplantation. Three patients died of sepsis and infection. The 5-year survival rate was 70% by the Kaplan-Meier method.

Conclusion

Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection using intraportal administration of DSLT. Donor type CD56+NK T cells may induce tolerance by a veto or an anti-idiotype network mechanism.     

ABO-incompatible deceased donor liver transplantation with the use of antigen-specific immunoadsorption and anti-CD20 monoclonal antibody

In patients with fulminant liver failure requiring emergency liver transplantation, the only donor organ that becomes available may be ABO incompatible. The risk of graft failure because of antibody-mediated acute rejection is high, but can be reduced by various means. We reported a deceased donor ABO-incompatible liver allograft recipient who was treated with antigen-specific immunoadsorption in combination with anti-CD20 monoclonal antibody and conventional plasmapheresis and immunosuppression. The patient was a 33-yr-old male with blood group A who presented with subacute liver failure of unknown aetiology and received a blood group AB liver graft. Pretransplant he underwent plasmapheresis and received one dose of rituximab. The immunosuppressive regimen consisted of methylprednisolone, tacrolimus and mycophenolate mofetil. Despite regular post-operative plasmapheresis sessions, anti-B antibody titres increased. Antigen-specific immunoadsorption with depletion of anti-B antibodies was performed from day nine to day 17. Thereafter, anti-B IgM and IgG antibody titres remained low. After one month the patient was reoperated with hepaticojejunostomy because of bile duct necrosis and with reconstruction of a stenotic hepatic artery. A mild rejection was successfully treated with methylprednisolone four months post-transplant. At six months post-transplant there was a stricture of the biliary-enteric anastomosis, but the graft was well functioning. We conclude that antigen-specific immunoadsorption can be an important adjuvant therapy to control recipient anti-A/B antibody levels and prevent acute rejection in ABO-incompatible deceased donor liver transplantation.     

Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation

Background

A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established.

Methods

We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m²) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6–12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab.

Results

Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients.

Conclusions

These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.     

Antibody-mediated rejection after adult ABO-incompatible liver transplantation remedied by gamma-globulin bolus infusion combined with plasmapheresis

Adult ABO-incompatible liver transplantation has been known to be associated with markedly desperate outcomes. Antibody-mediated rejection (AMR) has been recognized as one of the primary causes of these desperate outcomes, but its clinical features and significance have not been well understood. Recently, some clinicians have succeeded in improving the outcome of adult ABO-incompatible liver transplantation. However, in some transplant patients undergoing these treatments, AMR has still led to graft losses. We recently encountered two patients suffering from AMR after adult ABO-incompatible liver transplantation and remedied their conditions with various therapeutic modalities including direct hepatic infusion therapy and gamma-globulin bolus infusion therapy combined with plasmapheresis. In this article, we describe the clinical features of these patients and the therapeutic strategies we applied. Furthermore, we show the histologic course of the recovery from AMR in the second patient, from whom we were able to extract serial liver biopsies.     

A novel approach to successful ABO-incompatible high-titer renal transplantation

BACKGROUND: Currently the long-term outcome among recipients of ABO-incompatible renal transplantations is excellent in Japan. However, previous reports have documented poor outcomes in patients with high (> 1:256) anti-A/B antibody titers pretreatment. The immunosuppressive protocol for ABO-incompatible high-titer renal transplantation has remained a medical challenge. METHODS: We treated 3 patients with high (> 1:512) anti-A/B antibody titers prior to ABO-incompatible renal transplantation. Our immunosuppressive protocol was initiated 1 month prior to surgery and included mycophenolate mofetil (1 g/d) and low-dose steroid (methylprednisolone [8 mg/d]). Two doses of the anti-CD20 antibody rituximab, (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6 to 8 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation combined with 2 doses of basiliximab. RESULT: With this protocol, the anti-A/B antibody was reduced to below 1:16 in all cases. All 3 patients underwent successful transplantation with a mean current serum creatinine of 1.32 mg/dL (range, 1.22-1.50 mg/dL). There were no episodes of antibody-mediated rejection. No serious complications or side effects were encountered. CONCLUSIONS: A preconditioning protocol consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression enabled ABO-incompatible renal transplantation in patients with high (> 1:512) anti-A/B antibody titer.     

ABO-incompatible liver transplantation with no immunological graft losses using total plasma exchange,splenectomy, and quadruple immunosuppression: Evidence for accommodation

ABO-incompatible liver transplants (LTX) have been associated with a high risk of antibody-mediated rejection, poor patient and graft survival, and a high risk of vascular thrombosis and ischemic bile duct complications. We used pretransplantation and posttransplantation double-volume total plasma exchange (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or mycophenolate mofetil, prednisone, cyclosporine or tacrolimus, and OKT3 induction) in 14 patients receiving ABO-incompatible LTX between June 1992 and February 2001: A₁ to O (seven), B to O (two), B to A (two), A to B (one), AB to A (one), and AB to O (one). Actuarial 1- and 5-year patient and graft survival rates are 71.4% and 61.2 % and 71.4% and 61.2%, respectively, with a mean follow-up of 62.9 ± 39.4 months. Ten acute cellular rejections occurred, and the mean time to the first episode was 62 ± 33 days. All were steroid sensitive. No antibody-mediated rejection or vascular thromboses occurred. Pretransplantation pre-TPE immunoglobulin (Ig) G mean isohemagglutinin titers were 262 ± 326, compared with pretransplantation post-TPE titers of 65 ± 103 (P = .04). Eight of nine patients with measurable titers before and after TPE achieved a reduction in titers. The mean number of posttransplantation TPE was 5.5 ± 4.1 (range, 0 to 12), and the last TPE was on postoperative day 9.4 ± 5.3. IgG isohemagglutinin titers 2 weeks posttransplantation had increased to 153 ± 309 (P = .03 compared with pretransplantation pre-TPE IgG). ABO-incompatible liver transplantations can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple immunosuppression. Recovery of isohemagglutinin antibody levels without humoral rejection suggests that accommodation may be the protective mechanism preventing late antibody-mediated rejection. (Liver Transpl 2003;9:22-30.)     

ABO-incompatible kidney transplantation using both A2 and non-A2 living donors

BACKGROUND: Given the scarcity of cadaveric organs, efforts are intensifying to increase the availability of living donors. The current study assessed the feasibility of using ABO-incompatible living-donor kidneys to expand the donor pool. METHODS: The authors performed 18 ABO-incompatible living-donor kidney transplants between May 1999 and April 2001. Ten patients received living-donor kidneys from A2 and eight patients received kidneys from non-A2 blood group donors. Immunosuppression consisted of Thymoglobulin antibody induction, tacrolimus, mycophenolate mofetil, and prednisone. Eight non-A2 and two A2 kidney recipients also received a pretransplant conditioning regimen of four plasmapheresis treatments followed by intravenous immunoglobulin and splenectomy at the time of transplantation. Antidonor blood group antibody titer was measured at baseline, pretransplant, at 1- to 3-month and 1-year follow-up, and at the time of diagnosis of antibody-mediated rejection. RESULTS: No hyperacute rejection episodes occurred. One-year graft and patient survival rates in the 18 ABO-incompatible recipients were only slightly lower than those of 81 patients who received ABO-compatible kidney transplants during the same period (89% vs. 96% and 94% vs. 99%, respectively). Glomerular filtration rate and serum creatinine levels did not differ between the groups. Antibody-mediated rejection occurred in 28% of ABO-incompatible recipients, and was reversible with plasmapheresis, intravenous immunoglobulin, and increasing immunosuppression in all patients except one. CONCLUSIONS: ABO-incompatible living donor kidney transplants can achieve an acceptable 1-year graft survival rate using an immunosuppressive regimen consisting of Thymoglobulin induction, tacrolimus, mycophenolate mofetil, and prednisone combined with pretransplant plasmapheresis, intravenous immunoglobulin, and splenectomy.     

An approach to ABO-incompatible liver transplantation in children.

Survival in ABO-incompatible (ABO-I) liver transplantation has been reported to be between 40% and 60%. Management techniques have included routine immunosuppression as well as prophylactic antilymphoblast globulin, pre- and posttransplant plasmapheresis (PLPH), and splenectomy. Over a 6-year period, 155 orthotopic liver transplants were performed in 139 pediatric patients. Seven children received an ABO-I allograft. In the latter transplants, immunosuppression consisted of triple-drug therapy (cyclosporine A, prednisone, and azathioprine) along with prospective double-volume PLPH for ABO titers (IgA and IgM) greater than or equal to 1:8. Splenectomy was not performed on any patient. One patient was refractory to PLPH and was treated with a hemofiltration system using an immunoadsorption cartridge with synthetic A group antigen. The overall survival for patients receiving ABO-I allografts was 57% (4/7), with a 67% (4/6) graft survival in those patients treated with PLPH. The graft survival for patients treated with prospective PLPH and MALG was 60% (3/5). There was a 60% incidence of rejection in those patients treated with prospective PLPH and these episodes were all mild (steroid bolus only). While ABO-I transplantation is a reasonable option in the emergency setting, further study is necessary before it should be routinely used to increase the general donor organ pool in pediatric liver transplantation.     

Successful liver transplantation across the ABO incompatibility barrier in 6 cases of biliary atresia

Background

The problem of ABO-incompatible liver transplantation still remains unsolved in older children. In this article, we report on our experience of 6 successful ABO-incompatible liver transplantations in patients with biliary atresia.

Material and Methods

Six patients (ABO incompatibility type A→O:1 case, B→O:2 cases, A→B:3 cases) were enrolled in this study; 3 patients were aged approximately 1 year and the other 3 ranged in age from 9 to 24 years at the time of transplantation. Each patient received perioperative plasma exchange, until the anti-donor blood-type antibody titers became less than 1:16, and also systemic multidrug immunosuppressive therapy (cyclophosphamide, prednisolone, and tacrolimus). We applied the protocol of intraportal infusion therapy (local administration of prostaglandin E₁, steroid, and gabexate mesilate via a portal vein catheter), splenectomy, and rituximab administration for the older group.

Results

Both the patient and graft survival rates remain at 100%, with the follow-up period of the patients ranging from 12 and 123 months. Acute cellular rejection occurred in 2 cases, and both were steroid sensitive. There was no incidence of humoral rejection. Although all cases developed viral infection, all recovered uneventfully with the administration of antiviral agents.

Conclusion

ABO-incompatible liver transplantation can be performed with a low risk of humoral rejection or late biliary complications using this combined antirejection strategy, even in older children.     

ABO-incompatible liver transplantation: a new therapeutic option for patients with acute liver failure in Chile

Different ways have been suggested to expand donor numbers for liver transplantation. Transplantation using ABO-incompatible hepatic grafts has recently been a controversial issue due to the high risk of hyperacute rejection mediated by preformed anti-ABO antibodies. We report three patients with acute liver failure who were transplanted with ABO-incompatible livers: A to O in two patients and A to B in one case. We used pre- and posttransplant total plasma exchange, splenectomy, and triple immunosuppression. All three patients are alive; one graft was lost, probably secondary to thrombotic microangiopathy with low isohemagglutinin titers of 1:8. One patient developed acute cellular rejection that was reversed with a bolus of methylprednisolone. No antibody-mediated rejection occurred. Financial and infectious considerations have to be considered. In our series, the final liver transplantation cost was higher than average for acute liver failure. Plasmapheresis has the highest cost of all the additional procedures. ABO-incompatible liver transplantation, because of the splenectomy it requires, has been associated with more infections due to encapsulated organisms. However, with splenectomy in our three patients, none had infections due to these bacteria. In our country, we do not consider ABO-incompatible liver transplantation as a first-line option, except for highly selected patients.     

血型不相容肝移植新型策略临床的应用

目的：探讨血型不相容肝移植新型策略运用的疗效。
方法：回顾性分析血型不相容同种异体原位肝移植4例临床资料,4例均为成人ABO血型不相容肝移植,3例AB型供给O型,1例AB型RH（+）供给A型RH（-）。采用术前设定的围术期新策略预防急性排斥反应,包括四联免疫抑制剂、选择性血浆置换、术后输注免疫球蛋白和前列腺素E1、术中切脾、降阶梯策略预防及治疗术后感染。
结果：1例患者术后第3天发生抗体介导的超急性排异反应,经血浆置换联合甲基强的松龙冲击治疗治愈;2例发生急性肾功衰,经床旁血液净化治愈;所有患者术后均发生感染并治愈,全部存活出院,随诊2~10个月,肝肾功正常。
结论：采用四联免疫抑制剂﹑术中切出脾脏﹑选择性血浆置换,输注免疫球蛋白及脂质体前列腺素E1及降阶梯抗感染治疗新策略,也许是提高跨血型肝移植成功率的有效办法之一。     

Japan's experience with living-donor kidney transplantation across ABO barriers

Given the severe shortage of deceased-donor organs in Japan, the use of living-donor kidney transplantation (LKT) strategies, such as ABO-incompatible living-donor kidney transplantation, has expanded rapidly. ABO-incompatible LKT was initially performed following splenectomy and antibody removal; however, immunosuppressive protocols for ABO-incompatible LKT have changed markedly over recent years in Japan. Mycophenolate mofetil, calcineurin inhibitors and corticosteroids are now used to achieve desensitization before transplantation, and thereby suppress acute antibody-mediated rejection. In addition, many institutions now use anti-CD20 antibody (rituximab) instead of splenectomy, which seems to have markedly reduced the incidence of acute antibody-mediated rejection. ABO-incompatible LKT recipients in Japan typically undergo 2-4 sessions of plasma exchange or double-filtration plasmapheresis before transplantation to remove anti-ABO antibodies. In contrast to many Western countries, antibody removal is not routinely performed after kidney transplantation in Japan. Among 1,012 ABO-incompatible LKTs carried out at 92 Japanese institutions during the period 1989-2006, 1-year, 3-year, 5-year and 10-year patient survival rates were 95%, 93%, 91% and 87%, respectively, and the corresponding graft survival rates were 90%, 86%, 80% and 63%, respectively. These data indicate that the outcomes of ABO-incompatible LKT are comparable to those of ABO-compatible LKT. This Review summarizes Japan's experience with ABO-incompatible LKT.     

Excellent outcome of ABO-incompatible living kidney transplantation under pretransplantation immunosuppression with tacrolimus, mycophenolate mofetil, and steroid

INTRODUCTION: ABO-incompatible living kidney transplantation (LKT) has been performed to widen the indications for kidney transplantation. Since 2001, using a 7-day period of pretransplantation immunosuppression with tacrolimus (FK) plus mycophenolate mofetil (MMF) plus methylprednisolone (MP), we have observed a marked reduction in acute humoral/vascular rejection without any serious complications. PATIENTS AND METHODS: Forty-five adult patients underwent ABO-incompatible LKT at our institute between January 2000 and September 2002. There were 20 men and 25 women of mean age 33 years. Plasmapheresis was performed to remove anti-AB antibodies prior to kidney transplantation. In 2000, 13 patients were treated with FK plus MMF plus MP without 7-day pretransplantation immunosuppression (group 1). Since January 2001, we have administered FK (0.1 mg/kg/d) plus MMF (1-2 g/d) plus MP (125 mg/d) concomitantly with plasmapheresis starting from 7 days before transplantation in 32 patients (group 2). Splenectomy was performed at the time of kidney transplantation in all patients. RESULTS: Patient survival rate was 100% in both treatment groups. Graft survival rate was 92% and 97% in groups 1 and 2, respectively. One patient in group 1 lost the graft due to severe pancreatitis and 1 patient in group 2, due to severe humoral rejection. The incidence of acute rejection was 56% and 19% in group 1 and group 2, respectively. No patient experienced any lethal infectious complication. CONCLUSION: Pretransplantation immunosuppression for 7 days using FK, MMF, and MP in ABO-incompatible LKT provides an excellent outcome without severe infectious complications.