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


METHODS
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).


RESULTS
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).


CONCLUSIONS
We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.
Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. nyoshi@koto.kpu-m.ac.jp
N
N
Yoshimura
H
H
Ushigome
M
M
Matsuyama
S
S
Nobori
T
T
Suzuki
K
K
Sakai
H
H
Okajima
M
M
Okamoto
D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use; D000077552:Basiliximab; D015415:Biomarkers / Q000097:blood; D001787:Blood Group Incompatibility / Q000276:immunology*; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007564:Japan; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012263:Ribonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab; D013156:Splenectomy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000998:Antiviral Agents; D015415:Biomarkers; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D012263:Ribonucleosides; D000069283:Rituximab; C010052:mizoribine; D000077552:Basiliximab; D003404:Creatinine