Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
Regensburg Center for Interventional Immunology, University Hospital Regensburg, Regensburg, Germany.
Ann Hematol. 2019 Oct;98(10):2399-2405. doi: 10.1007/s00277-019-03768-x. Epub 2019 Aug 3.
Rituximab was recently described also as first-line therapy of chronic graft-versus-host disease (cGvHD). We retrospectively analyzed the efficacy and safety of all patients receiving rituximab for treatment of cGvHD between 2005 and 2016 at the Regensburg University transplant center with a median follow-up after rituximab therapy of 2.8 years. Responses of 29 allogeneic stem cell-transplanted patients (median age 49) with previous failure of response to steroids including one patient after donor lymphocyte infusion were assessed. Three months after rituximab application, the overall response rate was 31% (7% complete (n = 2) and 24% partial remission (n = 7)). At 12 months, overall survival was 72% (n = 21) and failure-free survival was 24% (n = 7). We further analyzed associations of rituximab response with clinical characteristics showing a higher response rate in steroid-dependent cGvHD patients (89% of 9 responding compared to steroid refractory patients (11% responding)). However, this difference was not statistically significant. Seven patients (24%) (including four lethal infectious complications) developed serious infections requiring hospitalization within 1-9 months after rituximab therapy exclusively in patients failing to respond to rituximab. In conclusion, rituximab appears to be an effective treatment of cGvHD especially in steroid dependent patients, but identification of biomarker predicting response will be crucial to avoid long-term infectious morbidity and mortality in non-responders.
利妥昔单抗最近也被描述为慢性移植物抗宿主病（cGvHD）的一线治疗药物。我们回顾性分析了 2005 年至 2016 年在雷根斯堡大学移植中心接受利妥昔单抗治疗的所有 cGvHD 患者的疗效和安全性，在利妥昔单抗治疗后中位随访 2.8 年。评估了 29 名接受同种异体干细胞移植的患者（中位年龄 49 岁）对先前对包括供者淋巴细胞输注后在内的类固醇反应失败的反应，其中 1 名患者接受了利妥昔单抗治疗。利妥昔单抗应用 3 个月后，总缓解率为 31%（完全缓解 7%（n=2）和部分缓解 24%（n=7））。12 个月时，总生存率为 72%（n=21），无失败生存率为 24%（n=7）。我们进一步分析了利妥昔单抗反应与临床特征的相关性，结果显示，在依赖类固醇的 cGvHD 患者中，利妥昔单抗的反应率更高（9 例缓解的患者中 89%，而类固醇难治性患者中 11%）。然而，这一差异无统计学意义。7 名患者（24%）（包括 4 例致命性感染并发症）在利妥昔单抗治疗后 1-9 个月内出现严重感染，需要住院治疗，仅在对利妥昔单抗无反应的患者中出现。结论：利妥昔单抗似乎是 cGvHD 的有效治疗方法，尤其是在依赖类固醇的患者中，但识别预测反应的生物标志物对于避免无反应者的长期感染发病率和死亡率至关重要。
