Clinical outcomes in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD) are generally poor, with a high mortality rate and limited therapeutic options. Here we report our updated investigational experience with mesenchymal stromal cell (MSC) therapy with remestemcel-L in a multicenter expanded access protocol (ClinicalTrials.gov identifier NCT00759018) in 241 children with aGVHD who failed to respond to steroids with or without other secondary and tertiary immunosuppressive therapies. A total of 241 children with grade B-D SR-aGVHD were enrolled at 50 sites in 8 countries and received 8 biweekly i.v. infusions of human MSCs, 2 × 106 per kg for 4 weeks, with an option for an additional 4 weekly infusions after day +28 for subjects who achieved either a partial response (PR) or mixed response. The mean age of the subjects was 9.6 years; 39% were female, and 60% were white. Most of the subjects had grade C (30%) or grade D (50%) disease, and in most cases, the subjects had failed to respond to other immunosuppressive agents after failing steroids. The primary endpoint was overall response (OR; the sum of complete response [CR] and PR) at day +28. Across all subjects, a 28-day OR was observed in 157 patients (65.1%), with 34 (14.1%) achieving CR and 123 (51.3%) achieving PR. Stratified by aGVHD grade at baseline, the OR rate at day +28 was 72.9% for patients with aGVHD grade B, 67.1% for those with aGVHD grade C, and 60.8% for those with aGVHD grade D. Survival through day +100, a secondary endpoint of the study, was 66.9% (n = 160 of 239). Importantly, survival through day +100 was significantly greater in subjects who achieved a day +28 OR compared with nonresponders (82.1% versus 38.6%; P < .001, log-rank test). Remestemcel-L safety was generally well tolerated, with no infusional toxicity and no identified safety concerns. In summary, this update to the remestemcel-L expanded access program confirms the reported clinical and survival benefits of remestemcel-L therapy in children with aGVHD who have exhausted all conventional therapeutic options.

中文翻译：

---

研究 275：更新了 Remestemcel-L 治疗儿童类固醇难治性急性移植物抗宿主病的扩大使用计划。


患有类固醇难治性急性移植物抗宿主病（SR-aGVHD）的儿童的临床结果通常较差，死亡率高且治疗选择有限。在这里，我们报告了我们在多中心扩展访问方案（ClinicalTrials.gov 标识符 NCT00759018）中使用 remestemcel-L 进行间充质基质细胞 (MSC) 治疗的最新研究经验，该研究对 241 名患有 aGVHD 的儿童进行了研究，这些儿童对类固醇没有反应，无论是否有其他二级和三级治疗免疫抑制疗法。共有 241 名患有 BD SR-aGVHD 级的儿童在 8 个国家的 50 个地点入组，每两周接受 8 次人类 MSC 静脉输注，每公斤 2 × 106 次，持续 4 周，并可选择在一天后额外每周输注 4 次。 28 对于获得部分反应 (PR) 或混合反应的受试者。受试者的平均年龄为 9.6 岁； 39%是女性，60%是白人。大多数受试者患有 C 级（30%）或 D 级（50%）疾病，并且在大多数情况下，受试者在类固醇失败后对其他免疫抑制剂没有反应。主要终点是第+28天的总体缓解（OR；完全缓解[CR]和PR之和）。在所有受试者中，157 名患者 (65.1%) 观察到 28 天 OR，其中 34 名患者 (14.1%) 实现 CR，123 名患者 (51.3%) 实现 PR。按基线时的 aGVHD 等级分层，+28 天时的 OR 率为，aGVHD B 级患者为 72.9%，aGVHD C 级患者为 67.1%，aGVHD D 级患者为 60.8%。+100 天的生存期，a该研究的次要终点为 66.9%（n = 239 人中的 160 人）。重要的是，与无应答者相比，达到+28天OR的受试者在+100天的生存率显着更高（82.1%对38.6%；P< .001，对数秩检验）。 Remestemcel-L 的安全性总体上具有良好的耐受性，没有输注毒性，也没有确定的安全问题。总之，remestemcel-L 扩大使用计划的更新证实了 remestemcel-L 疗法对已用尽所有常规治疗方案的 aGVHD 儿童的临床和生存益处。