B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation

Abstract

Although the effectiveness of rituximab has been reported in ABO blood group (ABO)-incompatible (ABO-I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO-I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B-cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO-I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B-cell study of the spleen, another 4 patients undergoing ABO-I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABOcompatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti-donor blood-type antibody titer was lower, and clinical and pathological antibody-mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody-mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO-I LDLT patients. Liver Transpl 13:579-588, 2007.

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

“…Several previous studies revealed that the effect of RIT on B cells in peripheral blood was very rapid, eliminating cells within 48-72 hours, and persisted for several months in transplant recipients (25). Furthermore, most data indicate that a single dose of RIT, as opposed to repeated doses, is sufficient for sustained suppression of B cells in peripheral blood (5,9,25,26). Consequently, repeated dosing of RIT may be unnecessary and may increase the risk of serious infection due to prolonged hypogammaglobulinemia.…”

“…Egawa et al (9) suggested that the timing of RIT administration was closely related to the rebound rise of IA titer. They emphasized early RIT prophylaxis, with the assumption that TPE immediately after RIT infusion would diminish the effect; however, only sparse data are available to evaluate the impact of TPE on the pharmacokinetic properties of RIT.…”

Current aspects of ABO-incompatible liver transplantation

“…Namely, we first reported the use of rituximab in LDLT recipients in 2005 [9], and described the successful treatment of rejection episodes in a patient who had not responded to other forms of treatment. Some other reports also supported the effectiveness of rituximab against antibody mediated rejection [21]. Recently, Egawa et al reported the recommended timing and doses of rituximab for ABO-I LDLT recipients (U).…”

ABO-Incompatible Liver Transplantation in Acute Liver Failure: A Single Portuguese Center Study

“…Pre-and postoperative plasmapheresis targeted isoagglutinin titers of at most 1:16, with or without IVIG and rituximab which were used to deplete cells producing IgM antibodies and those mediating HLA antibody-drives rejection episodes. 13,24,29 Although splenectomy has been used in desensitization protocols for ABOi transplantation, 21 it seems that AMR can be avoided with scheduled rituximab prophylaxis or multidrug immunosuppression. 14,23 Splenectomy avoidance decreases the risk of portal vein thrombosis 19 and long-term lethal infections.…”

“…6,13,14,19 -21 or by immunoadsorption 22,23 with adjunctive treatment by splenectomy and/or rituximab. 4,5,14,14,24 In 2009, our insitution implemented the current protocol for ABOi LT for patients with AHF and multiorganic failure (MOF) who are judged to be unable to wait for a compatible graft.…”