Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from two pediatric cases and review of literature.

IF 2.4 Q1 PEDIATRICS
Lina Driouk, Robert Schmitt, Anke Peters, Sabine Heine, Hermann Josef Girschick, Brigitte Strahm, Charlotte M Niemeyer, Carsten Speckmann
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引用次数: 11

Abstract

Background: Immune-mediated cytopenias (AIC) are challenging complications following allogeneic hematopoietic stem cell transplantation (HSCT). While broad-acting immunosuppressive agents like corticosteroids are often standard of care, several novel therapies which target specific immunological pathways have recently been developed and provide hope for patients with steroid-refractory courses and may limit long-term toxicity. The successful off-label use of the plasma cell depleting anti-CD38 antibody daratumumab was published in several case reports, suggesting efficacy, i.e., in patients with antibody-mediated AIC refractory to previous B cell depletion. We want to share our experience with two children, whom we treated with daratumumab, including one fatal course with uncontrolled disease. Given the absence of substantial data from HSCT registries or prospective trials, we furthermore provide a critical review of the literature on daratumumab treatment of AIC.

Case presentations: Patient 1 (P1), an 11-year-old girl with lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency who developed immune-mediated thrombocytopenia (AIT) from day +58 after HSCT, showed a complete response to daratumumab after the fourth of six total daratumumab doses. She remains transfusion independent for over a year of follow-up. Previously, her thrombocytopenia was refractory to corticosteroids, rituximab, intravenous immunoglobulins (IVIG), eltrombopag, cyclosporine A, and sirolimus. Patient 2 (P2), a 6-year-old boy with CD40 ligand (CD40L) deficiency, developed both AIT and hemolytic anemia (AIHA) after HSCT on days +58 and +83, respectively, and was also treated with daratumumab after being previously refractory to prednisolone, rituximab, and IVIG. Yet, he did neither respond to daratumumab nor the concomitantly administered methyprednisolone pulse, plasmapheresis, and eculizumab and succumbed due to refractory disease.

Conclusion: Reviewing the literature on the use of daratumumab for refractory AIC post-HSCT, we consider daratumumab a promising agent for this life-threatening disorder: ten of the twelve patients reached transfusion independency in the literature. However, treatment failures are likely to be underreported. Thus, controlled trials are needed to explore the safety and efficacy of daratumumab in this rare post-HSCT complication.

Abstract Image

Abstract Image

达拉单抗治疗造血干细胞移植后免疫介导的细胞减少症:两个儿科病例的经验和文献综述
背景:免疫介导的细胞减少症(AIC)是同种异体造血干细胞移植(HSCT)后具有挑战性的并发症。虽然像皮质类固醇这样的广谱免疫抑制剂通常是标准的治疗方法,但最近开发了一些针对特定免疫途径的新疗法,为类固醇难治性病程的患者提供了希望,并可能限制长期毒性。血浆细胞消耗抗cd38抗体daratumumab在适应症外的成功使用已发表在几例病例报告中,表明其有效性,即抗体介导的AIC对既往B细胞消耗难治性患者。我们想与我们用达拉单抗治疗的两个孩子分享我们的经验,其中包括一个疾病无法控制的致命病程。鉴于缺乏HSCT注册或前瞻性试验的大量数据,我们进一步对daratumumab治疗AIC的文献进行了批判性回顾。病例介绍:患者1 (P1)是一名11岁的女孩,患有脂多糖反应性和米色样锚蛋白(LRBA)缺乏症,在HSCT后第58天出现免疫介导的血小板减少症(AIT),在6次达拉图单抗总剂量的第4次后显示对达拉图单抗完全缓解。在一年多的随访中,她一直没有输血。此前,她的血小板减少症对皮质类固醇、利妥昔单抗、静脉注射免疫球蛋白(IVIG)、埃曲巴格、环孢素A和西罗莫司都是难治性的。患者2 (P2),一名患有CD40配体(CD40L)缺乏症的6岁男孩,在HSCT后分别在+58天和+83天出现AIT和溶血性贫血(AIHA),并且在先前对强的松龙,利妥昔单抗和IVIG难治后也接受了daratumumab治疗。然而,他对daratumumab和同时给予的甲泼尼龙脉冲、血浆置换和eculizumab均无反应,并因难治性疾病而死亡。结论:回顾关于在hsct后使用daratumumab治疗难治性AIC的文献,我们认为daratumumab是治疗这种危及生命疾病的有希望的药物:文献中12例患者中有10例达到了输血独立。然而,治疗失败可能被低估了。因此,需要对照试验来探索达拉单抗治疗这种罕见的移植后并发症的安全性和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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