ABO-incompatible Recipients Research Articles

The low dose of rituximab in ABO-incompatible kidney transplantation without a splenectomy: a single-center experience

A new protocol for ABO-incompatible (ABO-i) kidney transplantation including rituximab was introduced in January 2005 in our institute. This study reviewed the results and evaluated the use of low-dose rituximab in ABO-i kidney transplantation. Seventy-four de novo ABO-i kidney transplantations were performed at Tokyo Women's Medical University between January 2005 and August 2010. The immunosuppressive protocol was consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone. All the patients received induction therapy with basiliximab. The pre-conditioning protocol included double-filtration plasmapheresis and a single dose of rituximab. A dose of 500 mg/body rituximab was initially employed and yielded excellent results (Group I, n = 24). Afterward, the dose of rituximab was reduced to 200 mg/body in January 2007 (Group II, n = 50). Seventy-four de novo ABO-i recipients were treated with this protocol, and all patients underwent kidney transplantation successfully. Effective elimination of the peripheral blood CD19 cells was observed in both groups. However, the peripheral blood CD19 levels were still low in both groups at 24 months after treatment. The patients in Group II showed excellent results similar to Group I. These results suggest that the low dose of rituximab (200 mg/body) is the sufficient dose in ABO-i kidney transplantation.

Equivalent Outcomes for Pediatric Heart Transplantation Recipients: ABO-Blood Group Incompatible versus ABO-Compatible

ABO-blood group incompatible infant heart transplantation has had excellent short-term outcomes. Uncertainties about long-term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO-incompatible recipients. ABO-incompatible (n = 35) and ABO-compatible (n = 45) infant heart transplantation recipients (< or =14 months old, 1996-2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor-specific antibodies against blood group antigens, in only two ABO-incompatible patients were these antibodies implicated in antibody-mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow-up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO-blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO-compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor-specific isohemagglutinins and the implications for graft accommodation are warranted.

ABO-mismatched platelet transfusions: Strategies to mitigate patient exposure to naturally occurring hemolytic antibodies

Clinically significant hemolysis is a rare but potentially severe complication of administering an ABO-mismatched platelet transfusion. Platelet products from Group O donors, particularly single donor platelets (SDP) are most commonly implicated in these reactions. This is due to the presence of unusually high titers of anti-A which can be found in the plasma of some Group O donors and the large plasma volume of SDPs. These products can cause significant hemolysis when infused into a Group A or AB recipient. Random donor platelets from Group O donors have also been implicated. In practice, platelets are frequently transfused across ABO barriers though, ideally, in order to prevent or mitigate these reactions, platelet transfusions that are matched for ABO should be administered. However, limited availability of donor platelets as well as an abundance of Group O donors makes this a difficult standard to adhere to since often out-of group products are the only ones available. Methods to improve the safety of Group O products have focused on defining a safe level of isohemagglutinins so that the risk of hemolysis is alleviated when mismatched products are transfused. Determining the critical titer which defines a level above which a mismatched product should not be administered has been challenging. Non-standardized methods of isohemagglutinin titering and varying reports in the literature where products with a wide range of titers have been implicated in acute hemolytic transfusion reactions have made it difficult to determine a cut-off for labeling a product as high titer and thereby restricting its use to O recipients. Standards in the US place the responsibility for designing and implementing policies for the use of mismatched platelet products on each individual hospital transfusion service. Compliance requires only that there be an existing written policy which addresses the transfusion of products containing incompatible ABO antibodies but no specific procedures are required. In sharp contrast, European strategies have defined the low-end titer for which an out-of-group transfusion should not be given to an ABO-incompatible recipient. This testing is performed centrally at the Blood Centers who then make the determination on the status of a “dangerous donor”. The progress in this European strategy may serve the US to stimulate a re-examination of its practices and policies for the advancement of platelet transfusion safety.

Absence of Donor‐Specific Anti‐HLA Antibodies After ABO‐Incompatible Heart Transplantation in Infancy: Altered Immunity or Age?

Specific B-cell tolerance toward donor blood group antigens develops in infants after ABO-incompatible heart transplantation, whereas their immune response toward protein antigens such as HLA has not been investigated. We assessed de novo HLA-antibodies in 122 patients after pediatric thoracic transplantation (28 ABO-incompatible) and 36 controls. Median age at transplantation was 1.7 years (1 day to 17.8 year) and samples were collected at median 3.48 years after transplantation. Antibodies were detected against HLA-class I in 21 patients (17.2%), class II in 18 (14.8%) and against both classes in 10 (8.2%). Using single-antigen beads, donor-specific antibodies (DSAs) were identified in six patients (all class II, one additional class I). Patients with DSAs were significantly older at time of transplantation. In patients who had undergone pretransplant cardiac surgeries, class II antibodies were more frequent, although use of homografts or mechanical heart support had no influence. DSAs were absent in ABO-incompatible recipients and class II antibodies were significantly less frequent than in children with ABO-compatible transplants. This difference was present also when comparing only children transplanted below 2 years of age. Therefore, tolerance toward the donor blood group appears to be associated with an altered response to HLA beyond age-related effects.

Is splenectomy a dyslipidemic intervention? Experimental response of serum lipids to different diets and operations

Spleen removal may be recommended during organ transplantation in ABO-incompatible recipients as well as for hypoperfusion of the grafted liver, besides conventional surgical indications, but elevation of serum lipids has been observed in certain contexts. Aiming to analyze the influence of two dietary regimens on lipid profile, an experimental study was conducted. Male Wistar rats (n = 86, 333.0 +/- 32.2 g) were divided in four groups: group 1: controls; group 2: sham operation; group 3: total splenectomy; group 4: subtotal splenectomy with upper pole preservation; subgroups A (cholesterol reducing chow) and B (cholesterol-rich mixture) were established, and diet was given during 90 days. Total cholesterol (Tchol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and triglycerides were documented. After total splenectomy, hyperlipidemia ensued with cholesterol-reducing chow. Tchol, LDL, VLDL, triglycerides, and HDL changed from 56.4 +/- 9.2, 24.6 +/- 4.7, 9.7 +/- 2.2, 48.6 +/- 11.1, and 22.4 +/- 4.3 mg/dL to 66.9 +/- 11.4, 29.9 +/- 5.9, 10.9 +/- 2.3, 54.3 +/- 11.4, and 26.1 +/- 5.1 mg/dL, respectively. Upper pole preservation inhibited abnormalities of Tchol, HDL, VLDL, and triglycerides, and LDL decreased (23.6 +/- 4.9 vs. 22.1 +/- 5.1, P = 0.002). Higher concentrations were triggered by splenectomy and cholesterol-enriched diet (Tchol 59.4 +/- 10.1 vs. 83.9 +/- 14.3 mg/dL, P = 0.000), and upper-pole preservation diminished without abolishing hyperlipidemia (Tchol 55.9 +/- 10.0 vs. 62.3 +/- 7.8, P = 0.002). After splenectomy, hyperlipidemia occurred with both diets. Preservation of the upper pole tended to correct dyslipidemia in modality A and to attenuate it in subgroup B.

ABO-Incompatible Heart Transplantation in Infants: Analysis of the United Network for Organ Sharing Database

ABO-incompatible heart transplantation, traditionally contraindicated because of the risk of hyperacute rejection, has been used selectively in recent years. Infants have limited production of isohemagglutinins, which may lower the risk of hyperacute rejection. A large national database was used to analyze the effect of ABO incompatibility on outcomes after heart transplantation in infants. Heart transplant recipients aged younger than 1 year reported to the United Network for Organ Sharing from 1999 to 2007 were divided according to donor-recipient ABO incompatibility or compatibility. Outcomes included Kaplan-Meier survival and hyperacute rejection. Propensity-adjusted Cox regression modeling was used to identify predictors of mortality. Of 591 infants that underwent heart transplantation, 35 (6%) received allografts from ABO-incompatible donors. ABO-incompatible recipients trended toward more congenital heart disease (71% vs 66%; p = 0.06) and were less likely to have dilated cardiomyopathy (11% vs 29%; p = 0.02). One ABO-incompatible infant had hyperacute rejection requiring retransplantation. No ABO-incompatible infant and 2 ABO-compatible infants died from hyperacute rejection. Survival was similar at 3 years. Propensity-adjusted Cox regression analysis demonstrated that ABO-incompatibility did not predict mortality (hazard ratio, 3.61; 95% confidence interval, 0.26-49.0; p = 0.33). ABO-incompatible heart transplantation can be performed safely in infants without greater incidence of hyperacute rejection. ABO-incompatible heart transplantation should be strongly considered in infants to maximize donor organ utilization and reduce waiting-list mortality.

Potential Applications of Extracorporeal Photopheresis in Liver Transplantation

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy performed through a temporary peripheral venous access with documented efficacy in heart and renal transplantation. We originally reported that ECP represented a valuable alternative to treat graft rejection in selected liver transplant (OLT) recipients. We have investigated potential applications of ECP for prophylaxis of allograft rejection. The first field explored was the use of ECP for delayed introduction of calcineurin inhibitors (CNI) among high-risk OLT recipients seeking to avoid CNI toxicity. In 42 consecutive patients that we assigned to prophylaxis with ECP, we were able to delay CNI introduction after postoperative day 8 in one-third of them. The second field was the use of ECP for prophylaxis of acute cellular rejection among ABO-incompatible OLT recipients. In our experience, none of 11 patients treated with ECP developed a cell-mediated rejection. The third field was ECP application in hepatitis C virus-positive patients seeking to reduce the immunosuppressive burden and improve sustainability and efficacy of preemptive antiviral treatment with interferon and ribavirin. Among 78 consecutive patients, we were able to start preemptive antiviral treatment in 69.2% of them at a median time from OLT of 14 days (range = 7 to 130 days). Thirty-six (66.7%) patients completed the treatment course with an end of treatment virological response of 50.0% and a sustained virological response of 38.9%. These preliminary results await validation in larger prospective studies with longer follow-up periods.

Infectious complications associated with the use of rituximab for ABO‐incompatible and positive cross‐match renal transplant recipients

Immunosuppressive protocols for ABO-incompatible (ABOI) and positive cross-match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients.

Impact of ABO incompatibility on engraftment and transfusion requirement after unrelated cord blood transplantation: a single institute experience in Japan

The impact of ABO incompatibility between donor and recipient on engraftment and transfusion requirement was studied in 95 adults who underwent unrelated cord blood transplantation (CBT). The patients included 27 ABO-identical, 29 minor, 21 major and 18 bidirectional ABO-incompatible recipients. Neutrophil engraftment did not differ between ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients (hazard ratio (HR) 1.17, P=0.48). Cumulative incidence of platelet engraftment in ABO-identical/minor ABO-incompatible recipients was higher than in major/bidirectional ABO-incompatible recipients (HR 1.88, P=0.013). In addition, fewer platelet transfusions were required during the first 60 days after CBT in ABO-identical/minor ABO-incompatible recipients (HR 0.80, P=0.040). RBC engraftment did not differ between the two groups (HR 1.25, P=0.33). However, fewer RBC transfusions were required in ABO-identical/minor ABO-incompatible recipients than in major/bidirectional ABO-incompatible recipients (HR 0.74, P<0.005). No patients developed pure red-cell aplasia after CBT. These results indicate that ABO incompatibility affected platelet engraftment and transfusion requirement of RBC and platelet in CBT recipients. Further studies including larger patient numbers are required to elucidate the impact of ABO incompatibility on the clinical outcome of CBT.

In ABO-incompatible renal transplant recipients, tacrolimus plus mycophenolate mofetil (MMF) is superior to older immunosuppressant regimens,

In ABO-incompatible renal transplant recipients, tacrolimus plus mycophenolate mofetil (MMF) is superior to older immunosuppressant regimens,

The Transplantation Society – New Key Opinion Leaders of Tomorrow 2006

One of the new initiatives taken by the immediate past president of The Transplantation Society, KJ Wood, is to introduce a new series of meetings named ‘New Key Opinion Leaders of Tomorrow’. The Transplantation Society invites the leading young investigators in the field of transplantation to participate in this meeting together with the present leaders of the field. The key objective of this meeting is to identify the potential key opinion leaders of tomorrow. Each presentation during the meeting was jointly given by the senior and junior investigators. The meeting in Buenos Aires covered six main topics on clinical, translational and basic transplantation. These included: innate immunity and inflammation; transplant infectious diseases; tumour and transplantation; medical and ethical aspects of transplantation; dendritic cells (stimulating and manipulating the immune response to a transplant); and ABO incompatible donor recipient pairs. This report focuses on the emerging biological therapeutics and their ramifications on clinical transplantation.

ABO-Incompatible Kidney Transplantation with and without Splenectomy

The letter to the editor from Dr. Mitsuhata et al. raises interesting points with regard to the role of splenectomy in ABO-incompatible (ABOI) kidney transplants. The authors contend that the classification of ABOI kidney transplant recipients as “high risk” should not be made on the basis of baseline antibody titer. The association of humoral rejection with baseline antidonor blood group antibody titer in splenectomized ABOI recipients not undergoing posttransplant plasmapheresis has been reported by Shimmura et al., who found a 70% humoral rejection rate in patients with baseline titer ≥128 and 20% in those with titers ≤1:64 (1). These findings are similar to those of our report in which rejection occurred in 12% of patients with titers <1:64, while 83% of those with titers exceeding 1:64 rejected (2). Interestingly, Shimmura et al. have recently reported that posttransplant plasmapheresis to maintain a low titer in conjunction with splenectomy is effective in preventing humoral rejection in ABOI recipients with very high baseline titers (3). In their letter, Mitsuhata et al. refer to their Brief Communication describing their use of mycophenolate mofetil during four weeks preceding ABOI transplantation in 18 patients compared to 18 patients who did not receive pretransplant mycophenolate mofetil (4). In their report, all patients underwent antibody lowering therapy with plasmapheresis or plasma exchange. No comment was made as to whether or not recipients underwent splenectomy, although their current letter to the editor implies that they did. They report improved allograft survival six months after transplant in the pretreated group, although the humoral rejection rate was comparable. The causes for allograft loss in the pretreatment group were not reported, nor were baseline antidonor blood group antibody titers. The authors indicate that on the day of transplantation antidonor blood group antibody titers ranging from 1–128, although not specifically reported. Given our admittedly smaller experience in ABOI kidney transplantation, we would be very reluctant to proceed to transplantation at the time the recipient's titer exceeded 1:16, and our practice is to continue to perform plasmapheresis until achieving a titer ≤1:8 on the day of transplantation. An important point is that the antibody titer depends strongly on the method used to measure it. It is possible that the antibody measurement technique used by Mitsuhata et al. differs from the technique reported in our investigation. The authors present their opinion that the benefits of transplantation without splenectomy are outweighed by the psychological, physical, and economic burden posed by posttransplant plasmapheresis and/or anti-CD20 antibody therapy. Our opinion is that with aggressive posttransplant antibody monitoring and therapy to maintain low titer during the first two weeks after transplantation, humoral rejection is an unusual complication in the large majority of ABOI kidney transplants. We also feel that the life long advantage of avoiding splenectomy exceeds the disadvantage of posttransplant therapy during the first one to two weeks after transplantation. Finally, the authors refer to the important fact that other potentially injurious antibodies with donor reactivity may also complicate ABOI transplantation, similar to ABO compatible transplants, and we agree. James Gloor Department of Internal Medicine and Nephrology Mayo Clinic Rochester, MN Mark Stegall Division of Transplantation Surgery Mayo Clinic Rochester, MN

Usage of Deoxyspergualin on Steroid-Resistant Acute Rejection in Living Donor Liver Transplantation

Deoxyspergualin (DSG) is an immunosuppressive agent used to treat steroid-resistant acute rejection after kidney transplantation. But in the case of acute rejection after liver transplantation, DSG was reported effective in just a few cases. From July 1991 to November 2005, 96 patients underwent living donor liver transplantation (LDLTx) in our institution. Of them, 9 patients, including 4 ABO incompatible recipients, are presented. Rejection symptoms that did not respond to steroid pulse therapy (methylprednisolone, 10-20 mg/kg/day for 3 days) and were treated with DSG (3 or 5 mg/kg/day) for 4 to 14 days together with a maintenance dose of the steroid. Among them, five responded to treatment with DSG, two did not respond and the other two patients were not evaluated. Six of the nine patients are symptom free at present. Complications such as leukopenia and thrombocytopenia were successfully treated with granulocyte-colony stimulating factor or by platelet transfusion. No recipient died as a direct consequence of the complications induced by DSG. DSG proved effective and safe for some of the LDLTx recipients with steroid-resistant acute rejection but it was not effective for the treatment of accelerated humoral rejection in ABO incompatible recipients.

Successful Results After 5 Years of Tacrolimus Therapy in ABO-Incompatible Kidney Transplantation in Japan

In Japan, living donor kidney transplantation accounts for about 80% of all kidney transplants. This is in contrast to the United States and Europe, where transplantation of organs from cadaveric or brain-dead donors is more common. This study analyzed the results of 5 years of experience with tacrolimus in Japan, focusing on the efficacy of the drug in improving patient and graft survival in patients who underwent transplantation with ABO-incompatible kidney grafts. Of the 1542 evaluable patients, 1281 patients received grafts from living donors. Of these, 177 patients received kidneys from ABO-incompatible donors and 981 patients received kidneys from ABO-compatible donors. Graft survival rates in ABO-incompatible recipients ranged from 90.7% at 1 year to 80.5% at 5 years. Subsequent graft survival rates in ABO-compatible recipients were 98.1% and 92.9%, respectively ( P < .001 between groups). Patient survival rates at 5 years were 93.2% in ABO-incompatible recipients and 98.1% in ABO-compatible recipients. The rejection rate for kidneys from ABO-compatible donors was 27.8%, while for ABO-incompatible donors the rejection rate was 45.2%. The excellent outcome from this study demonstrates that even suboptimal ABO-incompatible donors can be used successfully as a source of kidneys when using tacrolimus as the immunosuppressive regimen. This may go some way to addressing the shortage of kidney donors in Japan.

New Strategy for ABO-Incompatible Living Donor Liver Transplantation With Anti-CD20 Antibody (Rituximab) and Plasma Exchange

It is more difficult to control humoral rejection in living donor liver transplantations (LDLT) across the ABO blood group barrier than in matched or compatible combinations. We achieved excellent results in ABO-incompatible transplantation with novel immunosuppressive regimens and plasma exchange (PE). Among 82 LDLT were 10 cases of ABO-incompatible recipients, including three who were administered rituximab for rescue or prophylactic therapy. Pretransplantation PE was performed as necessary to maintain hemagglutinin titers below 1:16 and posttransplantation PE was performed when there were signs of hyperacute rejection associated with high titers. Induction immunosuppression consisted of FK506, steroid, mycophenolate mofetil (MMF), and rituximab. The first patient was administered rituximab with deoxyspergualin (DSG), steroid pulse therapy, and PE on postoperative day (POD) 7, because of biopsy-proven humoral acute rejection. The titers and LFTs improved drastically. The second and third patients were administered rituximab just after the operation with other routine immunosuppressants for prophylaxis of hyperacute rejection. The second patient showed a slight deterioration in LFTs with an elevated titer, which normalized after steroid pulse therapy and PE. The third patient had no episodes of rejection. At present, that is 27, 17, and 6 months after the operations respectively, the 3 transplant recipients are in stable condition.

Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked immunosorbent assay after renal transplantation across the blood barrier: High-dose immunoglobulin administration blocks IgM rather than IgG anti-blood type antibodies

We used an enzyme linked immunosorbent assay (ELISA) to investigate the presence of subtypes of anti-blood-type antibodies in patients with biopsy-proven humoral rejection after ABO-incompatible renal transplantation. High agglutinin IgG and IgM anti-blood type antibodies from 12 ABO-incompatible recipients with vascular rejection were separately assessed using an ELISA. Patients who exhibited excellent renal function despite high agglutinin titers of anti-blood-type antibodies( n = 8) were also examined. All 12 rejection patients exhibited highly elevated titers of IgG and IgM, while the eight stable patients exhibited only slightly elevated IgG titers, but not IgM. IgG and IgM titers did not change after plasmapheresis and steroid pulse therapy, whereas IVIg treatment significantly blocked both IgG and IgM, with IgM being blocked to a larger extent than IgG. Blocking of IgM seems to play an important role in improving ABO-incompatible grafts.

Antibody Revisited

Antibody Revisited

NEW STRATEGY FOR THE ABO-INCOMPATIBLE LIVING DONOR LIVER TRANSPLANTATION WITH ANTI-CD20 ANTIBODY (RITUXIMAB) AND PLASMA EXCHANGE

P520 Aims: The donor shortage problem encouraged us to perform living donor liver transplantation (LDLT) across the ABO blood barrier. The survival rate in ABO-incompatible transplantations was much poorer than in ABO-compatible recipients for the early experiences, but the introduction of novel immunosuppressive regimens and PE has yielded excellent results in ABO-incompatible transplantations. We have successfully performed 3 cases of ABO-incompatible LDLT by using rituximab. Methods: In our institution we experienced 10 ABO-incompatible recipients out of 79 LDLT and 3 out of 10 recipients were administered rituximab for rescue or prophylactic therapy. The age range of the 10 recipients was 7 months to 54 years, with median age of 12.8 years. IgM and IgG hemagglutinin titers were measured before and after Tx using serial dilution in saline. Pre-Tx PE was performed as necessary to maintain hemaggulutinin titers below 1:16 and post-Tx PE was performed when it was diagnosed as hyperacute rejection with high titers. Induction immunosuppression consisted of FK506, steroid and MMF. Results: Nine of the 10 recipients and all the 3 recipients who were administered rituximab were alive. Case1 : A 22 months old girl whose primary disease was BA was performed LDLT from her father (A to O). She was also performed PE for twice before Tx in order to reduce titers 16 or below. From POD 3 the titers and LFTs were elevated despite the PE. On POD 7 needle graft biopsy revealed the hyperacute rejection and she was treated by rituximab, DSG and steroid pulse therapy. Her titers and LFTs were improved drastically and she was discharged on POD 74. CD19 positive lymphocytes in her peripheral blood were less than 1% until 3 month after Tx. Currently, 22 months after Tx, she is in stable condition. Case2 : A 42 year old woman whose primary disease was PBC was performed LDLT from her brother in law (B to O). She was performed PE for 7 times before Tx because of the high titer (1:512) and was administered rituximab prophylactic just after Tx. She also had splenectomy and intrahepatic artery infusion of PGE1 and steroid for 2 weeks. One week after Tx the titers were elevated with slight deterioration of LFTs, steroid pulse with PE improved the LFTs. She was discharged on POD 102 due to biliary leakage. CD19 positive lymphocytes in her peripheral blood were less than 1% until 8 month after Tx. Currently, 12 months after Tx, she is in stable condition. Case3 : A 54 year old woman whose primary disease was LC(B) with HCC was performed LDLT from her son (A to O). She was performed PE for 3 times before Tx and was administered rituximab prophylactic just after Tx. Because her hepatic artery was dissected during the Tx, she had intraportal infusion of PGE1 and steroid for 2 weeks and she also had splenectomy. Until 1 month after Tx her LFTs was stable and no sings of rejection was occurred. CD19 positive lymphocytes in her peripheral blood were 6 % after 1 month. Conclusions: Rituximab has the possibility to become the new strategy for the ABO-incompatible liver transplantation.

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

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. 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. 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. 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.

ABO-INCOMPATIBLE RENAL TRANSPLANTATION

From recent works, it can be concluded that renal transplantation across ABO incompatibility is acceptable if no other donor is available. Patient and graft survivals are nearly equal to those of ABO-compatible renal transplantation. Despite removal of ABO blood group antibodies before transplantation, hyperacute rejection may occur in some cases. Acute humoral rejection is the most frequent type of early rejection in an ABO-incompatible recipient, but most of these crises are controllable with the most effective antirejection therapy. Further immunopathologic studies are needed to clarify the rejection mechanism in the ABO-incompatible renal transplants. To obtain a successful outcome, immunologic preparation, including reduction of anti-A and anti-B antibody titers and splenectomy, is recommended, along with careful monitoring of antibodies, platelet counts, complement, and kidney function.