New protocol of immunosuppression for liver transplantation across ABO barrier: The use of Rituximab, hepatic arterial infusion, and preservation of spleen

New protocol of immunosuppression for liver transplantation across ABO barrier: The use of Rituximab, hepatic arterial infusion, and preservation of spleen
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DOI:
10.1016/j.transproceed.2005.03.148
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发表时间:
2005-05-01
影响因子:
0.9
通讯作者:
Tanaka, K
Tanaka, K
中科院分区:
医学4区
文献类型:
--
作者:
Yoshizawa, A;Sakamoto, S;Tanaka, K

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导论. ABO血型不合(ABO-I)活体肝移植(LDLT)是一项挑战。直到2000年,全身性多药免疫抑制和脾切除术是金标准,结果不佳。经门静脉导管局部给予前列腺素E1(PGE 1)和类固醇显著提高了生存率,从20%提高到60%,但门静脉血栓成为问题(35%)。为了解决这个问题,使用肝动脉(HA)导管代替PV导管,并省略了脾切除术。尽管PV血栓问题得到解决,但ABO抗体滴度显著升高,并发生了2例无法控制的体液排斥(HR)。在这项研究中,利妥昔单抗,而不是脾切除术,以减少抗体。我们报告了利妥昔单抗预防ABO-I LDLT的疗效。8名患者接受。LDLT前2 - 14天使用利妥昔单抗。在手术过程中,脾脏被保留。LDLT后,除了他克莫司和类固醇组成的免疫抑制方案外,还通过HA导管给予甲基强的松龙和PGE 1 2至3周。连续测量抗体滴度。无临床HR。2例患者死于与HR无关的并发症。与未行脾切除术/利妥昔单抗的患者相比,抗体滴度下降。从外周血中清除B细胞(CD 19)长达3个月。巨细胞病毒感染较脾切除术患者减少(P = 0.085)。利妥昔单抗预防和HA输注治疗预防了临床HR,这可能为克服肝移植中ABO血型障碍提供突破。
Introduction. An ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) is a challenge. Until 2000 systemic multidrug immunosuppression and splenectomy was the gold standard with poor results. Application of local administration with prostagrandin E1 (PGE1) and steroids via a portal vein (PV) catheter dramatically improved the survival from 20% to 60% but PV thrombus became a problem (35%). To solve it, an hepatic arterial (HA) catheter was used instead of a PV catheter and splenectomy was omitted. Although the PV thrombus problem was resolved, the ABO antibody titers significantly increased, and two cases of uncontrollable humoral rejection (HR) were experienced. In this study, Rituximab was introduced instead of splenectomy to decrease the antibody. We report the efficacy of prophylaxis with Rituximab for ABO-I LDLT.Methods. Eight patients received. Rituximab at 2 to 14 days before LDLT. During the operation, the spleen was preserved. Methylpredonisolone and PGE1 were administered via an HA catheter for 2 to 3 weeks after LDLT in addition to an immunosuppressive regimen consisting of tacrolimus and steroids. Antibody titers were measured serially.Result. There was no clinical HR. Two patients died of complications unrelated to HR. The antibody titer decreased compared to patients without splenectomy/rituximab. B cells (CD19) were depleted from peripheral blood for up to 3 months. Cytomegalovirus infections were decreased compared to patients with splenectomy (P = .085).Conclusion. Rituximab prophylaxis and HA infusion therapy prevented clinical HR, which may provide a breakthrough to overcome the ABO blood-type barrier in liver transplantation.