Moiseev I S, Morozova E V, Bykova T A, Paina O V, Smirnova A G, Dotsenko A A, Borzenkova E S, Galimov A N, Gudognikova Ya V, Ekushov K A, Kozhokar P V, Osipova A A, Pirogova O V, Rudakova T A, Klimova O U, Tcvetkov N Yu, Kulagin E A, Surkova E A, Lapin S V, Rodionov G G, Moiseev S I, Serov Yu A, Zubarovskaya L S, Afanasyev B V
R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, Pavlov University, Saint-Petersburg, Russian Federation.
Laboratory of Autoimmune Diagnostics, Pavlov University, Saint-Petersburg, Russian Federation.
Bone Marrow Transplant. 2020 Jul;55(7):1379-1387. doi: 10.1038/s41409-020-0834-4. Epub 2020 Feb 18.
Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.
急性和慢性类固醇难治性移植物抗宿主病（srGVHD）是异基因干细胞移植的一种危及生命的并发症。有许多关于病例系列的报告描述了芦可替尼在急性和慢性srGVHD中的疗效。我们对75例srGVHD患者（32例急性，43例慢性，41例成人，34例儿童）进行了一项前瞻性研究（NCT02997280）。慢性移植物抗宿主病患者83%病情严重，急性移植物抗宿主病患者66%为III-IV级疾病。急性移植物抗宿主病的总缓解率（ORR）为75%（95%CI 57-89%），慢性为81%（95%CI 67-92%）。急性组的总生存率为59%（95%CI 49-74%），慢性组为85%（95%CI 70-93%）。生存率较低的主要危险因素在急性形式中是III-IV级胃肠道受累（29%对93%，p = 0.0001），在慢性中是高疾病风险评分（65%对90%，p = 0.038）。毒性主要是血液学方面的，急性组和慢性组分别有79%和44%的III-IV级中性粒细胞减少。在总缓解率（p = 0.31，p = 0.35）、生存率（p = 0.44，p = 0.12）和毒性（p > 0.93）方面，成人和儿童之间没有差异。该研究表明，芦可替尼在急性和慢性srGVHD中是一种有效的选择，可用于成人和儿童。
