芦可替尼联合甲泼尼龙桥接异基因造血干细胞移植治疗儿童复发/难治性EB病毒相关性噬血细胞综合征的疗效

Clinical efficacy of Ruxolitinib in combination with Methylprednisolone as a bridge to allogeneic hematopoietic stem cell transplantation for relapse/refractory Epstein-Barr virus-associated hemophagocytic syndrome in pediatric patients

目的探讨应用Janus激酶抑制剂芦可替尼联合甲泼尼龙桥接异基因造血干细胞移植(allo-HSCT)治疗儿童复发/难治性EB病毒相关性噬血细胞综合征(EBV-AHS)的临床疗效和安全性。方法回顾性分析2018年8月至2020年2月于郑州大学第一附属医院儿科诊治的4例复发/难治性EBV-AHS患儿应用芦可替尼联合甲泼尼龙桥接allo-HSCT治疗的临床资料,对其病情特点、诊疗经过、经验体会及相关临床研究进展,进行分析和总结。结果4例复发/难治性EBV-AHS患儿中,2例病情部分缓解后应用小剂量芦可替尼联合甲泼尼龙维持治疗6~10周,疾病无进展,均顺利桥接allo-HSCT后存活;1例因无法耐受化疗,予大剂量芦可替尼联合甲泼尼龙治疗后,噬血生化指标明显好转,后桥接allo-HSCT,现移植后2个月,存活;1例患儿噬血细胞综合征复发后再化疗缓解,应用芦可替尼联合甲泼尼龙维持治疗,病情进展,治疗无效,行挽救性allo-HSCT,现移植后1年余,存活。除1例患儿出现轻度贫血外,余3例均未出现明显的芦可替尼药物相关不良反应。结论芦可替尼联合甲泼尼龙或可作为复发/难治性EBV-AHS的挽救性治疗和allo-HSCT术前桥接治疗的新手段,临床安全有效,耐受性好。

Objective To explore the clinical efficacy and safety of Ruxolitinib,a Janus kinase inhibitor,in combination with Methylprednisolone as a bridge to allogeneic hematopoietic stem cell transplantation(allo-HSCT)for relapsed/refractory Epstein-Barr virus-associated hemophagocytic syndrome(EBV-AHS)in pediatric patients.Methods The clinical data of 4 patients with relapsed/refractory EBV-AHS treated with Ruxolitinib in combination with Methylprednisolone as a bridge to allo-HSCT at the Department of Pediatrics,the First Affiliated Hospital of Zhengzhou University from August 2018 to February 2020 were retrospectively analyzed,and the disease characteristics,diagnosis and treatment process,clinical experience and related research progress were analyzed and summarized.Results Among 4 patients with relapsed/refractory EBV-AHS,2 patients were treated with low-dose Ruxolitinb in combination with Methylprednisolone for 6-10 weeks after partial remission.The disease did not progress,and they survived after being bridged to allo-HSCT.One patient was treated with large-dose Ruxolitinib in combination with Methylprednisolone due to the intolerance to chemotherapy,with the biochemical indicators of hemophagocytic syndrome significantly improved,and then the bridging to allo-HSCT was performed 2 months ago and this patient survived.One patient with EBV-AHS relapsed was relieved by chemotherapy again,then was given maintenance therapy with Ruxolitinib and Methylprednisolone,but the condition still progressed and the treatment was ineffective.This patient underwent allo-HSCT for salvage treatment more than 1 year ago and survived.Except that 1 patient developed mild anemia,the other 3 patients had no significant Ruxolitinib-related toxicities.Conclusions Ruxolitinib in combination with Methylprednisolone can be safely employed as a salvage treatment for pediatric patients with relapsed/refractory EBV-AHS and a bridge to allo-HSCT,which has favorable safety,efficacy and tolerance in clinical practice.