The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment.

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy. Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12). The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant). We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.

Yoshimura N ，Ushigome H ，Matsuyama M ，Nobori S ，Suzuki T ，Sakai K ，Okajima H ，Okamoto M ... -  《-》

Usefulness and safety of high-dose mizoribine on ABO-incompatible living related kidney transplantation using anti-CD20 and anti-CD25 antibodies without splenectomy: 3-year results.

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years. From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) . The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups. A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.

Yoshimura N ，Ushigome H ，Nobori S ，Suzuki T ，Sakai K ，Koshino K ，Nakamura T ，Nakao T ，Harada S ，Ito T ... -  《-》

The excellent outcomes of ABO-incompatible kidney transplantation with high titer (>×2048) using anti-CD20 and anti-CD25 antibody without splenectomy: two case reports.

Due to the shortage of deceased donors, we have expanded the indications for living-donor kidney transplantation (LKT) to include ABO-incompatible (ABO-i) individuals. However, which patients with high-titer anti-blood-group antibody can be transplanted successfully is unclear. Since 2009 we have performed 2 high-titer ABO-i spousal LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. In both cases, anti-type A antibody was 2048-fold before antibody removal. The immunosuppressive regimen consisted of 2 doses of anti-CD20 antibody (200 mg/body, day -14 to day -7), mycophenolate mofetil (1000 mg), prednisolone (10 mg starting from day -14), calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] starting from day -7), and 2 doses of anti-CD25 antibody (20 mg/body, days 0 and 4). Antibody removal by plasmapheresis was performed up to 4 times before LKT according to the antibody titer. The posttransplantation regimen consisted of mycophenolate mofetil or mizoribine as antimetabolite. A protocol biopsy was performed at 1 month and 1 year after LKT. The 60- and 62-year-old men had renal graft transplantation performed in the right hemipelvis without complication. After LKT, urinary output and serum creatinine decrease were within acceptable ranges without evidence of an acute rejection episode for 12 and 7 months, respectively. Patient and graft survival rates were 100%. A protocol biopsy at 1 month after LKT showed additional treatment to be unnecessary. Serious viral infection was not seen, even in the 1 patient who temporarily experienced positive changes in cytomegalovirus antigenemia. We obtained good clinical results among 2 high-titer ABO-i LKT using anti-CD20 and anti-CD25 antibodies without splenectomy, in conjunction with a calcineurin inhibitor plus mycophenolate mofetil or mizoribine.

Koshino K ，Okamoto M ，Sakai K ，Suzuki T ，Nobori S ，Matsuyama M ，Ushigome H ，Okajima H ，Yoshimura N ... -  《-》

Pinpoint targeted immunosuppression: anti-CD20/MMF desensitization with anti-CD25 in successful ABO-incompatible kidney transplantation without splenectomy.

Saito K ，Nakagawa Y ，Suwa M ，Kumagai N ，Tanikawa T ，Nishiyama T ，Ueno M ，Gejyo F ，Nishi S ，Takahashi K ... -  《xenotransplantation》

The beneficial effect of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids on CMV infection in renal transplant recipients.

Yoshimura N ，Ushigome H ，Akioka K ，Nobori S ，Suzuki T ，Sakai K ，Okamoto M ... -  《-》