anti-ABO Antibody Titer Research Articles

Impact of Baseline Anti-ABO Antibody Titer on Biliary Complications in ABO-Incompatible Living-Donor Liver Transplantation.

Background: Although advancements in desensitization protocols have led to increased ABO-incompatible (ABOi) living-donor liver transplantation (LDLT), a higher biliary complication rate remains a problem. This study evaluated the effect of baseline anti-ABO antibody titers before desensitization on biliary complications after ABOi LDLT. Methods: The study cohort comprised 116 patients in the ABO-compatible group (ABOc), 29 in the ABOi with the low titer (<1:128) group (ABOi-L), and 14 in the high titer (≥1:128) group (ABOi-H). Results: Biliary complications occurred more frequently in the ABOi-H group than in the ABOi-L and ABOc groups (7 [50.0%] vs. 8 [27.6%] and 24 [20.7%], respectively, p = 0.041). Biliary complication-free survival was significantly worse in the ABOi-H group than in the other groups (p = 0.043). Diffuse intrahepatic biliary strictures occurred more frequently in the ABOi-H group than in the other groups (p = 0.005). Multivariable analysis revealed that the high anti-ABO antibody titer (≥1:128) is an independent risk factor for biliary complications (hazard ratio 3.943 [1.635-9.506]; p = 0.002). Conclusions: A high baseline anti-ABO antibody titer (≥1:128), female sex, and hepatic artery complications are significant risk factors for biliary complications.

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Impact of baseline anti-ABO antibody titer on biliary complications following ABO-incompatible living donor liver transplantation

Experiences of performing ABO-incompatible kidney transplantation in Bangladesh.

BackgroundThe number of end-stage renal disease (ESRD) patients is increasing in Bangladesh. Currently, living kidney donation is the only viable option for transplantation in Bangladesh, and it is further restricted by ABO compatibility issues. We have performed ABO-incompatible kidney transplantations (ABOi KTs) in Bangladesh since 2018. This study examines our experiences with seven cases of ABOi KT.MethodsThe desensitization protocol included low-dose rituximab (100 mg/body) followed by plasma exchange (PEX), which was followed by a 5-g dose of intravenous immunoglobulin. Immunosuppression was undertaken using tacrolimus (0.1 mg/kg/day), mycophenolate mofetil (1,500 mg/day), and prednisolone (0.5 mg/kg/day). All patients received basiliximab for induction therapy.ResultsThe median baseline anti-ABO antibody titer was 164 (range, 132–1128). Transplantation was performed at a titer of ≤18. Our patients attended three to five PEX sessions before transplantation. Graft survival was 100% in the seven cases over a mean period of 22 months. The mean creatinine level was 204.6±47.4 µmol/L. Two patients were suspected of having developed acute rejection and received intravenous methylprednisolone, resulting in improved kidney function. One patient required posttransplant hemodialysis due to delayed graft function and subsequently improved. Infection was the most common complication experienced by ABOi KT patients. Two patients developed severe cytomegalovirus pneumonia and died with functioning grafts.ConclusionsABOi KT in Bangladesh will substantially expand the living kidney donor pool and bring hope to a large number of ESRD patients without ABO-compatible donors. However, the high cost and risk of acute rejection and infection remain major concerns.

ABO-incompatible liver transplantation using only rituximab for patients with low anti-ABO antibody titer.

Backgrounds/AimsGraft survival after ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has increased due to advances in desensitization methods. We analyzed early outcomes following ABOi LDLT using only rituximab without any additional desensitization methods in recipients with low anti-ABO antibody titers (≤1:32).MethodsTen adult patients underwent ABOi LDLT between September 2014 and December 2016. All patients were administered a single dose of rituximab (300 mg/m2) prior to LDLT. Three patients with baseline anti-ABO titer >1:32 underwent multiple sessions of plasmapheresis to reduce titers to <1:32 (rituximab+plasmapheresis, RP). Seven patients with low anti-ABO titer (≤1:32) did not undergo plasmapheresis (rituximab-only, RO). ABO-compatible LDLT patients during the same period were included for comparison (n=22).ResultsPost-transplantation titers were significantly lower in the RO than in the RP and showed no rebound rise (POD7 1.14±0.38 vs 28.0±31.7, p=0.04), (POD30 1.26±0.45 vs 108±107, p=0.02). There were no significant differences in rejection, biliary complications and infection between groups. There were no significant differences in outcome between the RO group and ABO-compatible except for infection.ConclusionsThis study shows that recipients with low baseline anti-ABO antibody titer (≤1:32) can undergo ABOi LDLT using conventional immunosuppression and rituximab alone.

P135 Living donor kidney paired donation transplantation: First report from Kingdom of Saudi Arabia

Aim Kidney paired donation (KPD) is an effective way to transplant patients with willing but incompatible donors. We report our experience with KPD through development of local Registry for incompatible pairs. Methods 62 recipients & their incompatible donors plus 3 non-directed donors were entered into KPD registry. Incompatibility was due to ABO-incompatibility (ABOi) in 25% & HLA-incompatibility (HLAi) in 75%. Patients with HLAi had cPRA between 60–99%. Antibodies with MFI of ⩾ 3000 by SAB assay were listed as unacceptable antigens. We used balanced, unbalanced & non-directed anonymous donors (NDAD). ABOi donors were accepted if patients had low titer ( ⩽ 16) of Isohemagglutinins. Amenable DSA for desensitization are those weak, single or multiple that yielded negative or weakly positive flow cross match ( Results 23 candidates (37%) were transplanted, enabling pre-emptive transplant in 1 patient. The longest chain was seven -ways domino chain initiated by a NDAD & ended in transplant of deceased donor listed patient with multiple access failure. Additional desensitization was used for 9 patients due to DSA and/ or positive FXM. 1 patient received TPE due to anti ABO antibody titer of 16. We had one case of DGF, AMR occurred in 2 patients & 1 patient had ACR. Graft function was good through follow-up time of 6–18 months but one patient died 8 months post-transplant due to refractory sepsis. Conclusions Although our series is early with 62 patients, transplant rate is excellent compared to other old programs(Netherlands, UK, & Canada) where the transplant rate were 37%, 29%, 44% respectively. This might be attributed to involving NDAD, accepting ABOi & combining desensitization for low level DSA in selected patients. Considering that 75% of the patients were highly sensitized yet received living transplants with excellent results, our experience demonstrates promising short-term outcomes. However, longer follow-up is needed to assess the impact of KPD on organ shortage & the outcome of highly sensitized patients transplanted through KPD program.

Donor Specific Antibody Negative Acute Antibody-Mediated Rejection under the Low Anti-ABO Antibody Titer after ABO Incompatible Liver Transplantation

Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation (ABOi-LT). Serum B cell counts and serum anti-ABO antibody titers are the main factors monitored to prevent AMR, and a desensitization protocol has been developed to overcome this problem. According to the 2016 Banff Working Group on Liver Allograft Criteria, the diagnosis of acute AMR requires the positive serum donor specific antibody (DSA). Clinical significance of histological findings of AMR in the absence of DSA is unclear. Here, we present the case of allograft injury like acute AMR under the absence of DSA after ABOi LDLT with the low titers of anti-ABO antibody and depleted serum CD19+ B cells. A 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. The patient received rituximab (300 mg/m2) 3 weeks before transplantation and then underwent three sessions of plasmapheresis. Pre-operative donor-specific antibody (DSA) and cross-matching were negative (donor blood type A+). The titers of anti-ABO antibodies decreased to 1:8 from 1:256, and serum CD19+ B cells were depleted before the operation. During improvement of liver function, acute AMR was observed in protocol biopsy on postoperative day 7; the CD19+ count was 0%, and anti-ABO antibody titers were 1:2. Despite treatment with three sessions of plasmapheresis and intravenous immunoglobulin (0.8 g/kg), the inflammatory reaction expanded. Histological findings were improved after steroid pulse therapy. Although, clinical significance of DSA (-) AMR is unclear, it has been shown that the treatment improves histopathologic changes in this case. In ABOi liver transplantation, investigations for immediate histologic allograft injury similar to acute AMR might be needed to know its clinical significance.

ABO-Incompatible Liver Transplantation Using only Rituximab for Patients with Low Anti-ABO Antibody Titer

Background Graft survival after ABO-incompatible living donor liver transplantation (LDLT) has increased due to advances in desensitization methods. We analyzed early outcomes following ABO-incompatible LDLT without plasmapheresis in recipients with low anti-ABO antibody titers (1:32). Methods Ten adult patients underwent ABO-incompatible LDLT between September 2014 and December 2016. All patients were administered a single dose of rituximab (300 mg/m2) prior to LDLT. Three patients with baseline anti-ABO titer >1:32 also underwent multiple sessions of plasmapheresis to reduce titers to 1:32 or lower (rituximab + plasmapheresis, RP). Seven patients with low anti-ABO titer (1:32) did not undergo plasmapheresis (rituximab-only, RO). Adult ABO-compatible LDLT patients during the same period were included for comparison (n=22). Results Post-transplantation titers were significantly lower in the RO than in the RP and showed no rebound rise (POD7 1.14±0.38 vs 28.0±31.7, p=0.04), (POD30 1.26±0.45 vs 108±107, p=0.02). There were no significant differences in rejection, biliary complications, or infection between the RO and RP group. There were no significant differences in outcome between the RO group and ABO-compatible except for rate of infection (RO: 57.1%; ABO-compatible: 9.1%; p=0.02). Conclusions This study shows that recipients with low baseline anti-ABO antibody titer (≤1:32) can undergo ABO-incompatible LDLT using conventional immunosuppression and rituximab alone.

Feasibility of Monotherapy by Rituximab Without Additional Desensitization in ABO-incompatible Living-Donor Liver Transplantation.

Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living-donor liver transplantation (ABO-i LDLT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion (LI) therapy were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT. Forty patients receiving ABO-i LDLT with rituximab were enrolled in this retrospective study. The patients were divided into 2 groups: the rituximab with pretransplant PP and posttransplant LI (RPL) group (n = 20) and the rituximab monotherapy (RM) without any additional treatment group (n = 20). The groups were then compared in terms of the rates of patient survival, antibody-mediated rejection (AMR), and infection. The 1-, 3-, and 5-year patient survival rates were 85%, 85%, and 85% in the RPL group and 89%, 80%, and 80% in the RM group, respectively. There was no significant difference in patient survival between the 2 groups. There were no episodes of AMR in either group. The RM group had a lower rate of fungal and viral infections than the RPL group. Pretransplant rituximab without additional treatments yielded satisfactory outcomes comparable to that with additional treatments, such as PP and LI.

Risk factors for postoperative bleeding in ABO-incompatible kidney transplantation.

The outcome of ABO-incompatible kidney transplantation (ABOi KT) has improved and is now comparable to that of ABO-compatible kidney transplantation (ABOc KT). However, ABOi KT may be associated with a higher risk of postoperative bleeding than ABOc KT. Seventy patients with ABOi KT were divided into a bleeding group (n=9) and non-bleeding group (n=61). General, immunologic, and hematological characteristics were compared to identify the risk factors for postoperative bleeding. Pre-emptive transplantation and a high pre-transplant blood urea nitrogen level were more common in the bleeding group (p=0.0176 and 0.023, respectively). A high anti-ABO antibody titer after plasmapheresis (median, ≥16; p=0.0226), a low platelet count of ≤100000/mm(3) after plasmapheresis (p=0.0289), a prolonged activated partial thromboplastin time (p=0.0073), and impaired platelet function (p=0.0274) were associated with an increased risk of bleeding after ABOi KT. Postoperative bleeding after ABOi KT was difficult to control and increased the risk of immediate graft loss (p=0.015). Our results suggest that changes in coagulability associated with uremia and plasmapheresis may increase the risk of bleeding after ABOi KT.

Fourteen Successful Consecutive Cases of ABO-Incompatible Living Donor Liver Transplantation: New Simplified Intravenous Immunoglobulin Protocol Without Local Infusion Therapy

Since various innovative strategies including local infusion therapy and rituximab have been introduced, the survivals and outcomes of recipients in ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) have remarkably improved. Thus, ABO-I LDLT can be a feasible therapeutic option for the patient with end-stage liver disease if an ABO-compatible donor is not available. Although most ABO-I protocols are based on rituximab, plasma exchange, and local infusion therapy, treatment strategies have been changing according to a center's preference or their results. Nonetheless, the consensus of the ABO-I LDLT protocol remains undetermined. Herein, we present our experience with new simple ABO-I LDLT protocol and the excellent results for 14 patients from January 2011 to May 2013. All patients were administrated a single dose of rituximab over 7 days before transplantation followed by plasma exchange to lower anti-ABO antibody titer ≤32. The basic immunosuppression protocol consisted of tacrolimus and steroids with mycophenolate mofetil starting 3 days before transplantation. Splenectomy was not performed routinely and local infusion therapy was not applied at the postoperative period. Instead, the patients received intravenous immunoglobulin (IVIG) after LDLT on days 1, 3, and 5. Neither antibody-mediated rejection nor biliary stricture were encountered in the patients, with a mean follow-up of 16.27 ± 9.4 months. This new simplified ABO-I LDLT protocol seems to prevent antibody-mediated rejection and could be considered as the safe and effective modality to overcome the ABO blood-type barrier in LDLT.

Current Issues in ABO-Incompatible Kidney Transplantation

Organ shortage is a critical issue in Korea as well as in other countries. In Korea, in 2013, the number of end-stage renal disease patients on the waiting list was 14,600; however, only 1,759 patients received transplantation during 2013. Recent advances in immunosuppression and antibody removal protocols have made ABO-incompatible kidney transplantation (ABO IKT) feasible, and have increased the opportunities for patients to undergo transplantation, especially for patients who do not have an ABO-compatible donor. The first ABO IKT was reported in 1955, but was unsuccessful due to the absence of an effective preparation protocol for antibody removal. In the 1980s, Alexandre used a protocol for removal of anti-ABO antibodies for the first time; however, the outcome was still inferior to that of ABO-compatible KT. Since 2000, with the advancement of immunosuppression and plasmapheresis, the outcome of ABO IKT has shown significant improvement and is now comparable to that of ABO-compatible KT. However, there are still several undetermined issues in ABO IKT. For example, issues regarding anti-ABO antibody titer, pretransplant desensitization method, immune suppressant regimen, and the role of C4d have still not been established. In this article, we reviewed the current status and protocol of ABO IKT and addressed to the undetermined issues in this field.

Use of Bortezomib as Anti-Humoral Therapy in Kidney Transplantation

This study aimed to investigate the effect of bortezomib in the desensitization and treatment of acute antibody mediated rejection (AAMR) in kidney transplantation. Nine patients who received bortezomib therapy for desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were included in this study. In the DSZ group, 2 patients required DSZ owing to positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the start of the treatment. In the AAMR group, 3 patients showed full recovery of allograft function after bortezomib use and decrease in donor specific anti-HLA antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and experienced allograft failure. In the DSZ group, negative conversion of T-CDC (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2 patients. In the case of ABO mismatch kidney transplantation, the anti-A/B antibody titer decreased to below the target (≤ 1:16) after bortezomib therapy. Therefore, bortezomib could be an alternative therapeutic option for desensitization and treatment of AAMR that is unresponsive to conventional therapies.

A Single Center Experience of ABO Incompatible Kidney Transplantation

Chi Lan Chang, M.D., Joon Heon Jeong, M.D., Jong Po Kim, M.D., Dong Ryeol Lee, M.D., Jin Min Kong, M.D. and Byung Chang Kim, M.D.. J Korean Soc Transplant 2012;26:261-8. https://doi.org/10.4285/jkstn.2012.26.4.261

Determination of Rituximab Dose According to Immunologic Risk in ABO-Incompatible Kidney Transplantation

The adequate rituximab (RTX) dosage in ABO-incompatible transplantation (ABO-IKT) remains undetermined. We used two kinds of RTX dosage groups [low RTX (100 mg/m2) and typical RTX (375 mg/m2) dosage groups] according to immunologic risks and investigated the change of B-cell, anti-ABO antibodies, and the clinical outcome in ABO-IKT according to the RTX dose. Fifteen patients with high immunologic risk [panel reactive antibody (PRA) > 50%, retransplant, AB to O transplant] were assigned to typical RTX group and 17 patients without risk were assigned to low RTX group. We compared the changes of B-cell, anti-ABO antibody titer, required number of plasmapheresis (PP), and the clinical outcome after transplantation between the two groups. After infusion of RTX, peripheral blood B-cell counts were successfully depleted to <1% in both groups. Before kidney transplantation (KT), the minimal number of PP to achieve the target titer (1:16) (2.6 ± 2.7 vs. 2.2 ± 2.5; p = 0.66) and the titer reduction rate of anti-ABO antibodies did not differ between the two groups (low RTX: 1.52 ± 1.21 vs. typical RTX: 1.53 ± 1.20, p = 0.94). After KT, anti-ABO antibody titer was suppressed less than 1:32 in both groups up to posttransplant 1 year. The allograft function and infectious complication did not differ between the two groups as well. In ABO-IKT, low RTX is comparable with typical RTX dosing with respect to B-cell depletion, antibody rebound suppression, the effect on clinical outcome in patients with low immunologic risk.

Successful ABO-Incompatible Kidney Transplantation with Antibody Removal and Standard Immunosuppression

ABO-incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus-based immunosuppressive regimen to contemporaneous ABO-compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7-14 days pretransplant). Antibody depletion was scheduled according to baseline anti-ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18-32). Eight rejection episodes (two antibody-mediated and six cellular) in ABOi recipients were successfully treated with biopsy-proven resolution. Latest median eGFR is 50 mL/min × 1.73 m² (IQR 40-64) for ABOi patients and 54 mL/min × 1.73 m² (IQR 44-66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end-stage kidney disease patients.

Comparison of Clinical Outcome between High and Low Baseline Anti-ABO Antibody Titers in ABO-Incompatible Kidney Transplantation

High baseline anti-ABO antibody titer is still an important obstacle for successful ABO-incompatible kidney transplantation (ABO IKT). This study aims to investigate the clinical outcome of ABO IKT in patients with a high baseline titer in comparison with patients with a low baseline titer. Fourteen patients who received ABO IKT at our center were classified as the high-titer group (≥1:256, n = 8) or the low-titer group (≤1:128, n = 6). We used a protocol composed of rituximab, plasmapheresis, and intravenous immunoglobulin (RTX/PP/IVIG). We compared the intensity of preparation, complications, and clinical outcome between the two groups. The high-titer group required more sessions of pretransplant (10.5 ± 3.5 vs. 6.0 ± 1.3 times, p = 0.01) and posttransplant (1.6 ± 1.8 vs. 0 ± 0 times) PP/IVIG than the low-titer group did. All patients from both groups showed immediate recovery of graft function. The antibody titer and allograft function in the high-titer group were stable and did not differ significantly from those of the low-titer group up to 1 year after kidney transplantation. There was no antibody-mediated rejection in either group during follow-up, but three cases of acute cellular rejection developed in the high-titer group. The high-titer group showed two cases of opportunistic viral infection (herpes gingivitis and cytomegalovirus viremia) and one case of graft loss due to postoperative bleeding. ABO IKT can be safely performed even in patients with a high baseline anti-ABO antibody titer, but the risk for infection and bleeding should be considered before transplantation.

Double-Filtration Plasmapheresis

It is well known that anti-ABO antibodies in the recipient's serum cause hyperacute rejection in ABO-incompatible kidney transplantation. To perform successful ABO-incompatible kidney transplantation, temporary elimination of the anti-ABO antibodies from the recipient's serum is mandatory. Several methods of removing anti-ABO antibodies have been reported: plasmapheresis or immunoadsorption is widely employed in ABO-incompatible kidney transplantation. Two plasmapheresis methods are available, namely, regular plasma exchange by centrifugation or a plasma separator, and double-filtration plasmapheresis (DFPP). DFPP was designed to selectively remove the immunoglobulin fraction from the serum and, as a result, to minimize the volume of substitution fluid required. In this procedure, we usually use 0.5-1.0 L of an 8% albumin solution as the replacement fluid. This is equivalent to 2.5-5.0 L of fresh plasma used in regular plasma exchange. For pretransplant preconditioning, we usually perform DFPP. Three immunosuppressive drugs, such as tacrolimus, mycophenolate mofetil, and methylprednisolone, are administered 7 days before renal transplantation. To remove anti-A and/or anti-B antibodies, the recipients receive 3 or 4 DFPP sessions before the transplantation until the anti-ABO antibody titers have decreased to < or =1:32. A low dose of rituximab (total dosage 200 mg) is given 7 days before renal transplantation and basiliximab is administered at the time of renal transplantation. Between 2005 and 2006, 39 patients were enrolled in this protocol, and only 1 patient could not undergo renal transplantation because their anti-ABO antibody titer was not reduced to the acceptance criterion of ABO-incompatible living-related kidney transplantation (ABO-ILKT), which is 32x dilution. The desensitization success rate using our pretransplant conditioning regimen was 97%. DFPP effectively and safely eliminated anti-ABO antibodies from ABO-incompatible kidney transplantation recipients and contributed to successful ABO-ILKT.

Experiences and problems pre‐operative anti‐CD20 monoclonal antibody infusion therapy with splenectomy and plasma exchange for ABO‐incompatible living‐donor liver transplantation

ABO-incompatible living-donor liver transplantation (LDLT) requires a reduction of the anti-ABO antibody titer to <16 before transplantation, which is usually achieved by pre-operative plasma exchange (PE) or double-filtration plasmapheresis. ABO-incompatible transplantations have been performed after a splenectomy with heavy drug immunosupression plus B-cell-specific drugs. Here, we evaluated a pre-transplantation infusion protocol with an anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible LDLT. Between March 2002 and December 2005, 73 adult patients underwent LDLT without retransplantation in our institution. Among these cases, 57 were ABO-identical, 11 were ABO-compatible and five were ABO-incompatible. The rituximab infusion protocol consisted of a weekly infusion of rituximab (375 mg/m(2)) for three wk, which was administered to three of the five ABO-incompatible LDLT patients. All three patients underwent a pre-operative PE, as well as a splenectomy during the operation. A triple immunosuppression protocol of tacrolimus, low-dose steroids and mycophenolate mofetil (1500 mg/d) was administered post-operatively. In addition, the patients received a continuous intra-arterial infusion of prostaglandin E(1) and methylprednisolone, and a continuous intra-portal infusion of a protease inhibitor for three and two wk after transplantation, respectively. After the first rituximab infusion, the peripheral blood CD19(+) B cell count rapidly decreased to <1%. All three patients treated with rituximab subsequently received an ABO-incompatible LDLT, with donor/recipient blood groups of B/O, A(1)/B and A(1)/O. In two cases, the ABO-antibody level transiently increased post-operatively, then decreased and remained low. Rituximab infusion therapy did not develop any direct side effect except for mild allergic reaction to the first infusion, but post-operatively all three patients suffered a cytomegalovirus and were successfully treated with ganciclovir, and one patient had a MRSA-positive intra-abdominal abscess. Two patients are currently alive at 20 and 18 months respectively, and show normal graft-liver function. But one patient died of sepsis because of intra-abdominal abscess. Although the protocol of rituximab administration is a conventional and safe regimen with no major side effects, the development of a new protocol is needed for prevention of the infection with bone suppression.

Successful Use of Anti-CD20 Monoclonal Antibody (Rituximab) for ABO-Incompatible Living-Related Liver Transplantation

Humoral rejection after ABO-incompatible liver transplantation often causes graft loss and a life-threatening situation. We used rituximab, which can eliminate B cells highly selectively, as an additional therapy for ABO-incompatible living-related liver transplantation. Patient 1 was a 1-year-old girl with biliary atresia. Her blood type was O, and the donor's was A. She underwent two plasma exchanges before liver transplantation and had triple immunosuppressants (mycophenolate mofetil, tacrolimus, and methylprednisolone). She was diagnosed with humoral rejection by needle biopsy on postoperative day 6. Rituximab was used for 3 days at 375, 187, and 187 mg/m(2) and successfully reduced the antibody titer, transaminase, and CD19(+) cells count in peripheral blood lymphocytes. The patient has not had any severe rejection, infection, or serious complications 2 years posttransplantation. Patient 2 was a 42-year-old woman with primary biliary cirrhosis. The blood type was O, and the donor's was B. She received three plasma exchanges, triple immunosuppressants, splenectomy, intraarterial anticoagulant therapy, and rituximab (375 mg/m(2) immediately after transplantation). The titer and CD19(+) cells count remained persistently low throughout the recovery course. She did not develop humoral rejection 1 year after transplantation. Rituximab efficiently reduces anti-ABO antibody titer by selectively eliminating B cells and is safe and effective against humoral rejection after ABO-incompatible liver transplantation.