Chavaz Lara, Cimasoni Laurent, Kremer Hovinga Johanna A, Coppo Paul, Ansari Marc
Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent Medicine, Geneva University Hospital, Geneva, Switzerland.
Cansearch Research Platform for Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Front Pediatr. 2024 Aug 21;12:1448801. doi: 10.3389/fped.2024.1448801. eCollection 2024.
The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections.
儿童免疫性血栓性血小板减少性紫癜（iTTP）的基础治疗是治疗性血浆置换（TPE）、皮质类固醇和利妥昔单抗联合使用。卡泊单抗是一种抗血管性血友病因子（VWF）纳米抗体分子，已被批准作为≥12岁成人和儿童iTTP的一线治疗药物。根据相关建议，在12岁以下儿童中使用卡泊单抗仍存在争议且未获上市许可。我们报告了首例iTTP儿科患者，根据ADAMTS13活性将卡泊单抗剂量调整为每日5毫克后成功治愈。我们还回顾了所有已发表的12岁以下儿童iTTP患者使用卡泊单抗治疗的病例。这是一名7岁女孩，患有临床血栓性微血管病，无腹泻和肾损伤。法国评分2分，血浆评分7分（高风险），怀疑为TTP，后来经严重降低的ADAMTS13活性（<5%）确诊。由于存在功能性ADAMTS13抑制剂，免疫性TTP与先天性TTP得以区分。第0天（D0）开始每日进行TPE和静脉注射皮质类固醇。第4天加用利妥昔单抗，由于每日TPE治疗效果不佳，我们考虑从第12天开始超说明书使用卡泊单抗。48小时内观察到临床反应，血小板计数显著增加。第62天ADAMTS13完全恢复。治疗期间未观察到重大不良事件。3个多月前她出院，血小板计数仍在正常范围内。在文献中，我们共确定了4例病例报告，描述了5名12岁以下iTTP患者使用卡泊单抗治疗的情况，成功率和耐受性均为100%。这些已发表的数据证明了系统使用卡泊单抗和利妥昔单抗作为12岁以下儿科iTTP一线治疗的有效性和安全性。因此，需要前瞻性数据来支持卡泊单抗在该亚组中的商业授权。在儿童中密切监测ADAMTS13活性对于限制卡泊单抗注射次数尤为重要。
