We conducted a randomized, placebo-controlled, double-blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti-thymocyte globulin induction would reduce de novo donor-specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year posttransplant. We analyzed peripheral blood lymphocytes by flow cytometry, serum for antibody development, and respiratory samples for viral infections using multiplex PCR. Of 45 subjects enrolled, 34 were transplanted and 27 randomized to rituximab (n = 15) or placebo (n = 12). No rituximab-treated subjects versus five placebo-treated subjects developed de novo DSA with mean fluorescence intensity >2000. There was no difference between treatment groups in time to the primary composite outcome endpoint (death, bronchiolitis obliterans syndrome [BOS] grade 0-p, obliterative bronchiolitis or listing for retransplant). A post-hoc analysis substituting more stringent chronic lung allograft dysfunction criteria for BOS 0-p showed no difference in outcome (p = .118). The incidence of adverse events including infection and rejection episodes was no different between treatment groups. Although the study was underpowered, we conclude that rituximab induction may have prevented early DSA development in pediatric lung transplant recipients without adverse effects and may improve outcomes (Clinical Trials: NCT02266888).

中文翻译：

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CTOTC-08：利妥昔单抗诱导减少抗体产生和改善小儿肺移植受者预后的多中心随机对照试验

我们对儿科肺移植受者进行了一项随机、安慰剂对照、双盲研究，假设利妥昔单抗联合兔抗胸腺细胞球蛋白诱导会减少新的供体特异性人类白细胞抗原抗体 (DSA) 的产生并改善结果。我们连续获得移植后至少一年的临床数据、血液和呼吸道样本。我们通过流式细胞术分析了外周血淋巴细胞、用于抗体开发的血清以及使用多重 PCR 分析了病毒感染的呼吸道样本。在登记的 45 名受试者中，34 名接受移植，27 名随机接受利妥昔单抗 ( n  = 15) 或安慰剂 ( n  = 12)。没有接受利妥昔单抗治疗的受试者与五名接受安慰剂治疗的受试者从头发展平均荧光强度 >2000 的 DSA。治疗组之间在达到主要复合结局终点（死亡、闭塞性细支气管炎综合征 [BOS] 0-p 级、闭塞性细支气管炎或再次移植上市）的时间上没有差异。用更严格的慢性肺同种异体移植物功能障碍标准代替 BOS 0-p 的事后分析显示结果没有差异 ( p  = .118)。包括感染和排斥事件在内的不良事件的发生率在治疗组之间没有差异。尽管该研究的功效不足，但我们得出结论，利妥昔单抗诱导可能已经阻止了儿科肺移植受者的早期 DSA 发展而没有不良影响，并且可能改善结果（临床试验：NCT02266888）。