Toyoda Hidemi, Deguchi Takao, Iwamoto Shotaro, Kihira Kentaro, Hori Hiroki, Komada Yoshihiro, Hirayama Masahiro
Department of Pediatrics, Mie University, School of Medicine, Tsu, Japan.
J Pediatr Hematol Oncol. 2018 Nov;40(8):e516-e518. doi: 10.1097/MPH.0000000000001276.
Recently, a new disease of lymphocyte homeostasis caused by somatic mosaicism for the RAS mutation has been discovered (known as RALD, RAS-associated leukoproliferative disorder). Since few cases have been reported in literature, the prognosis and standard treatment for autoimmune diseases associated with RALD remain poorly understood. Standard rituximab therapy (375 mg/m for 4 wk) is effective in patients with autoimmune diseases, but early recurrences are common. We highlight the potential for monthly administration of rituximab in a patient with autoimmune thrombocytopenia and hemolytic anemia associated with RALD. RALD was diagnosed in an 11-year-old girl following a 9-year history of severe hepatosplenomegaly and autoimmune cytopenias. Genetic analyses confirmed somatic mosaicism for the G13C KRAS mutation without an autoimmune lymphoproliferative syndrome-related gene mutation. Rituximab therapy was used because of the refractory character of the autoimmune cytopenias which failed to respond to steroids and other immunosuppressive agents. Her treatment consisted of weekly infusions of rituximab for 4 weeks followed by monthly rituximab for 11 months. She maintained her response in hematologic parameters for 2 years after monthly rituximab was ceased and her scores representing quality of life were improved. Rituximab could improve clinical responses and quality of life of the patients with RALD.
最近，一种由RAS突变的体细胞镶嵌现象引起的淋巴细胞内稳态新疾病被发现（称为RALD，RAS相关白细胞增殖性疾病）。由于文献中报道的病例很少，与RALD相关的自身免疫性疾病的预后和标准治疗仍知之甚少。标准的利妥昔单抗治疗（375mg/m²，共4周）对自身免疫性疾病患者有效，但早期复发很常见。我们强调了在一名患有与RALD相关的自身免疫性血小板减少症和溶血性贫血的患者中每月使用利妥昔单抗的可能性。一名11岁女孩在经历了9年的严重肝脾肿大和自身免疫性血细胞减少症后被诊断为RALD。基因分析证实存在G13C KRAS突变的体细胞镶嵌现象，且无自身免疫性淋巴细胞增殖综合征相关基因突变。由于自身免疫性血细胞减少症对类固醇和其他免疫抑制剂无效，具有难治性，因此使用了利妥昔单抗治疗。她的治疗包括每周输注利妥昔单抗4周，随后每月输注利妥昔单抗11个月。在停止每月输注利妥昔单抗后，她的血液学参数维持了2年的缓解，且代表生活质量的评分有所改善。利妥昔单抗可以改善RALD患者的临床反应和生活质量。
