Lastovytska Iryna, Heidenreich Silke, Klyuchnikov Evgeny, Niederwieser Christian, Gagelmann Nico, Richter Johanna, Massoud Radwan, Rathje Kristin, Perekhrestenko Tetiana, Zeck Gaby, Lück Catherina, Janson Dietlinde, Wolschke Christine, Ayuk Francis, Kröger Nicolaus
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf.
Haematologica. 2025 Jul 1;110(7):1536-1544. doi: 10.3324/haematol.2024.286824. Epub 2025 Mar 20.
We compared long-term outcomes in 78 patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) treated at the University Medical Center Hamburg, Germany, between December 2015 and August 2022 who received either ruxolitinib alone (Ruxo, N=29) or Ruxo plus extracorporeal photopheresis (Ruxo-ECP, N=49). Patients were well balanced between both arms except for SR-aGvHD grade IV which was higher in the Ruxo-ECP group (45% vs. 14%, P<0.001). In both cohorts, steroids were tapered rapidly, and median steroid treatment was 39 days in Ruxo and 35 days in Ruxo-ECP. The overall response rate including complete remissions (CR) of aGvHD at day 28 was 90% and 31% for Ruxo versus 86% and 0% (P<0.001, respectively) for Ruxo-ECP. At six months, partial remission (PR) and CR status of evaluable patients was 11% and 50% in Ruxo-ECP versus 10% and 40% after Ruxo alone, respectively (P=0.018). At 12 months, PR and CR status was 6% and 17% in the Ruxo group, but 82% and 64% (P<0.001) in the Ruxo-ECP cohort, and the cumulative incidence of chronic GvHD was significantly higher after Ruxo versus Ruxo-ECP at 49% (95% CI: 33-69%) versus 24% (95% CI: 15-38%) (P=0.01). Reconstitution of B cells occurred significantly earlier at one and three months in the Ruxo arm. No difference in 1-year non-relapse mortality, relapse, and 2-year overall survival was observed. Despite the limitations of this retrospective single- center study, the data suggest a better long-term control of aGvHD and less chronic GvHD at one year combining ruxolitinib with ECP compared to ruxolitinib alone in SR-aGvHD.
我们比较了2015年12月至2022年8月期间在德国汉堡大学医学中心接受治疗的78例类固醇难治性急性移植物抗宿主病（SR-aGvHD）患者的长期预后，这些患者分别单独接受鲁索替尼治疗（鲁索替尼组，N = 29）或鲁索替尼联合体外光化学疗法治疗（鲁索替尼-体外光化学疗法组，N = 49）。除了SR-aGvHD IV级在鲁索替尼-体外光化学疗法组中更高（45%对14%，P<0.001）外，两组患者在各方面基本均衡。在两个队列中，类固醇均迅速减量，鲁索替尼组的类固醇中位治疗时间为39天，鲁索替尼-体外光化学疗法组为35天。鲁索替尼组在第28天aGvHD的总体缓解率（包括完全缓解[CR]）为90%和31%，而鲁索替尼-体外光化学疗法组分别为86%和0%（P均<0.001）。在六个月时，可评估患者的部分缓解（PR）和CR状态在鲁索替尼-体外光化学疗法组中分别为11%和50%，而单独使用鲁索替尼组分别为10%和40%（P = 0.018）。在12个月时，鲁索替尼组的PR和CR状态分别为6%和17%，但在鲁索替尼-体外光化学疗法队列中分别为82%和64%（P<0.001），并且鲁索替尼组慢性移植物抗宿主病的累积发生率显著高于鲁索替尼-体外光化学疗法组，分别为49%（95%CI：33 - 69%）对24%（95%CI：15 - 38%）（P = 0.01）。鲁索替尼组B细胞的重建在1个月和3个月时明显更早发生。未观察到1年无复发生存率、复发率和2年总生存率的差异。尽管这项回顾性单中心研究存在局限性，但数据表明，与单独使用鲁索替尼相比，在SR-aGvHD中，将鲁索替尼与体外光化学疗法联合使用在1年时对aGvHD的长期控制更好，慢性移植物抗宿主病更少。
