Chen Wenting, Wang Zhi, Liu Zhouyang, Fu Bin, Xing Tingting, You Jianhua, Hu Jiong
Hainan General Hospital, Haikou, China.
Hainan Hospital of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Qionghai, China.
Ann Hematol. 2025 Feb;104(2):1241-1247. doi: 10.1007/s00277-024-06128-6. Epub 2024 Dec 11.
Belumosudil is a selective small molecule inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) indicated for patients with glucocorticoid-refractory chronic graft-versus-host disease (cGVHD). Despite its approval for ages 12-18, there is limited pediatric data available. This case series presents three 12-year-old patients with severe cGVHD who had failed multiple lines of therapy. Case #1 received treatment for 210 days with belumosudil, prednisone, cyclosporine A, mycophenolate mofetil, and ruxolitinib. Initial assessments showed skin and joint fascia involvement (National Institutes of Health score 3), along with oral cavity, ocular, and pulmonary involvement (score 2). Following treatment, all affected organs demonstrated at least a partial response (PR), with an overall assessment of PR. Case #2 was treated for 205 days with belumosudil, tacrolimus, and ruxolitinib. Baseline assessments indicated involvement of the skin and joint fascia (score 3), and the oral cavity and eyes (score 2). Most organs achieved PR or complete response (CR), resulting in an overall PR. Case #3 underwent 121 days of therapy with belumosudil, prednisone, and tacrolimus, showing similar baseline organ involvement as Case #2. The treatment resulted in an overall PR, with improvement noted in the skin, oral cavity, eyes, and joint fascia. The Lee cGVHD symptom scale scores improved meaningfully for all patients over time. There was no recurrence of the primary disease or any fatalities. Adverse events were limited to grade 1-2 severity. This case series indicates that belumosudil may be effective in 12-year-old pediatric patients with severe, multi-organ cGVHD refractory to multiple treatments. The findings suggest that belumosudil-based regimens can be feasible and well-tolerated in this population, providing preliminary evidence for its potential therapeutic effects in clinical management.
贝鲁莫司迪是一种选择性小分子Rho相关卷曲螺旋激酶2(ROCK2)抑制剂,适用于糖皮质激素难治性慢性移植物抗宿主病(cGVHD)患者。尽管已获批用于12至18岁患者,但可用的儿科数据有限。本病例系列介绍了三名12岁的严重cGVHD患者,他们接受了多线治疗均失败。病例1接受了210天的贝鲁莫司迪、泼尼松、环孢素A、霉酚酸酯和芦可替尼治疗。初始评估显示皮肤和关节筋膜受累(美国国立卫生研究院评分为3分),同时伴有口腔、眼部和肺部受累(评分为2分)。治疗后,所有受累器官均至少有部分缓解(PR),总体评估为PR。病例2接受了205天的贝鲁莫司迪、他克莫司和芦可替尼治疗。基线评估表明皮肤和关节筋膜受累(评分为3分),以及口腔和眼睛受累(评分为2分)。大多数器官达到PR或完全缓解(CR),总体为PR。病例3接受了121天的贝鲁莫司迪、泼尼松和他克莫司治疗,基线器官受累情况与病例2相似。治疗导致总体PR,皮肤、口腔、眼睛和关节筋膜均有改善。随着时间的推移,所有患者的李cGVHD症状量表评分均有显著改善。未出现原发性疾病复发或任何死亡情况。不良事件仅限于1 - 2级严重程度。本病例系列表明,贝鲁莫司迪可能对接受多种治疗难治的12岁严重多器官cGVHD儿科患者有效。研究结果表明,基于贝鲁莫司迪的治疗方案在该人群中可能可行且耐受性良好,为其在临床管理中的潜在治疗效果提供了初步证据。