Hamasaki Yuko, Aikawa Atsushi, Itabashi Yoshihiro, Muramatsu Masaki, Hyoudou Yoji, Shinoda Kazunobu, Takahashi Yusuke, Sakurabayashi Kei, Mizutani Toshihide, Oguchi Hideyo, Kawamura Takeshi, Sakai Ken, Shishido Seiichiro
From the Department of Nephrology and the Department of Pediatric Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan.
Exp Clin Transplant. 2019 Jan;17(Suppl 1):105-109. doi: 10.6002/ect.MESOT2018.O43.
Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients.
Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups.
In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function.
Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.
利妥昔单抗治疗策略在ABO血型不相容的小儿肾移植受者中有所不同。在此,我们展示了2剂利妥昔单抗的疗效以及ABO血型不相容小儿肾移植患者的后续结局。
我们对ABO血型不相容小儿肾移植受者的研究包括21例接受脱敏预处理的患者,其中在移植前10天和1天给予2剂100mg利妥昔单抗(利妥昔单抗组),以及14例接受了脾切除术但未使用利妥昔单抗的患者(脾切除术组)。两组均接受免疫抑制治疗。在移植期间及移植后4天给予巴利昔单抗。对移植前抗供体抗体滴度较高的患者进行双重滤过血浆置换和/或血浆置换程序。对利妥昔单抗组依次测量CD19阳性和CD20阳性B细胞。比较两组移植前后抗供体抗体的最高滴度、患者和移植物存活率、活检证实的排斥反应以及并发症/感染情况。
在利妥昔单抗组中,CD19和CD20阳性B细胞在移植时被清除,在3个月时持续清除,直至移植后1年低于5%。利妥昔单抗组移植后抗供体抗体的最高滴度显著下降(P <.001),但脾切除术组未下降(P = 0.174),移植后最高滴度显著低于脾切除术组(P <.001)。利妥昔单抗组无患者发生临床排斥反应,但脾切除术组有5例患者发生临床T细胞介导的排斥反应,其中2例还发生了抗体介导的排斥反应。利妥昔单抗组有6例发生巨细胞病毒血症但无巨细胞病毒病;然而,脾切除术组有5例受者发生巨细胞病毒病和病毒血症。在利妥昔单抗组中,3例发生迟发性中性粒细胞减少症。1名儿童死于肥厚性心肌病,移植物功能良好;其他所有患者均存活,移植物无失功。脾切除术组所有儿童均存活,尽管有2例移植物功能恶化。
2剂利妥昔单抗在长期B细胞清除以抑制抗供体抗体方面有效。必须考虑迟发性中性粒细胞减少症的可能性。