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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Usui
Masanobu
M
Department of Hepatobiliary Pancreatic Surgery, Mie University Hospital, Mie, Japan. m-usui@clin.medic.mie-u.ac.jp
Isaji
Shuji
S
Mizuno
Shugo
S
Sakurai
Hiroyuki
H
Uemoto
Shinji
S
D000017:ABO Blood-Group System; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D001787:Blood Group Incompatibility; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007262:Infusions, Intravenous; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D000069283:Rituximab