Faculty of Medicine, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.
J Transl Med. 2023 Nov 21;21(1):837. doi: 10.1186/s12967-023-04731-1.
Patients with steroid-refractory acute graft-versus-host disease (aGvHD) not tolerating/responding to ruxolitinib (RR-aGvHD) have a dismal prognosis.
We retrospectively assessed real-world outcomes of RR-aGvHD treated with the random-donor allogeneic MSC preparation MSC-FFM, available via Hospital Exemption in Germany. MSC-FFM is provided as frozen cell dispersion for administration as i.v. infusion immediately after thawing, at a recommended dose of 1-2 million MSCs/kg body weight in 4 once-weekly doses. 156 patients, 33 thereof children, received MSC-FFM; 5% had Grade II, 40% had Grade III, and 54% had Grade IV aGvHD. Median (range) number of prior therapies was 4 (1-10) in adults and 7 (2-11) in children.
The safety profile of MSC-FFM was consistent with previous reports for MSC therapies in general and MSC-FFM specifically. The overall response rate at Day 28 was 46% (95% confidence interval [CI] 36-55%) in adults and 64% (45-80%) in children; most responses were durable. Probability of overall survival at 6, 12 and 24 months was 47% (38-56%), 35% (27-44%) and 30% (22-39%) for adults, and 59% (40-74%), 42% (24-58%) and 35% (19-53%) for children, respectively (whole cohort: median OS 5.8 months).
A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, respectively (median 28 days). Our data thus suggest effectiveness of MSC-FFM in RR-aGvHD.
对接受鲁索利替尼（RR-aGvHD）治疗不耐受/无反应的类固醇难治性急性移植物抗宿主病（aGvHD）患者，预后较差。
我们回顾性评估了德国通过医院豁免获得的异体间充质干细胞制剂 MSC-FFM 治疗 RR-aGvHD 的真实世界结果。MSC-FFM 以冷冻细胞分散体的形式提供，解冻后立即通过静脉输注给药，推荐剂量为 1-200 万 MSC/kg 体重，分 4 次，每周 1 次。共 156 例患者（其中 33 例为儿童）接受了 MSC-FFM 治疗；5%为 II 级，40%为 III 级，54%为 IV 级 aGvHD。成人的中位（范围）既往治疗数为 4（1-10），儿童为 7（2-11）。
MSC-FFM 的安全性与以往关于 MSC 治疗的报告一致，特别是与 MSC-FFM 的报告一致。成人患者第 28 天的总缓解率为 46%（95%置信区间[CI] 36-55%），儿童为 64%（45-80%）；大多数缓解是持久的。成人患者 6、12 和 24 个月的总生存率分别为 47%（38-56%）、35%（27-44%）和 30%（22-39%），儿童患者分别为 59%（40-74%）、42%（24-58%）和 35%（19-53%）（全体患者：中位 OS 为 5.8 个月）。
最近一项关于 64 例未接受 MSC 治疗的 RR-aGvHD 成人患者的真实世界疗效分析报告称，分别有 20%、16%和 10%的患者在 6、12 和 24 个月后存活，中位时间为 28 天。因此，我们的数据表明 MSC-FFM 在 RR-aGvHD 中的有效性。
