Efficacy of Mesenchymal Stem Cells for the Treatment of Steroid-Refractory aGVHD

Background: Steroid-refractory acute graft vs. host disease (SR-aGVHD) remains a significant complication of allogenic hematopoietic stem cell transplantation (allo-HSCT). In this phase II-III multicenter clinical study we evaluated the efficacy and safety of MSCs(JR-031; JCR Pharmaceuticals Co., Ltd., Japan) for SR-aGVHD.

Method: 25 patients (age: 5-66 years, median 33years; male 15, female 10) who developed SR-aGVHD (grade III 22, grade IV 3) after allo-HSCT (Nov. 2011-Sept. 2012) were enrolled and given 8 biweekly infusions of 2x10⁶ cells/kg of JR-031 for 4 weeks, with an additional 4 infusions weekly after 28 days in patients with partial response (PR). They were followed up to 24 weeks.

Results: At 4 weeks after the first dose, 6 (24%) patients showed complete response (CR), 9 (36%) patients showed PR, 4 (16%) patients showed mixed response (MR) and 1(4%)patient showed no change (NC). During 24 weeks of observation period, 12 (48%) patients achieved durable CR (CR >=28days). As for response by organ, 80% (16/20) of GI, 66.7% (8/12) of skin and 66.7%(4/6) of liver GVHD completely responded (stage 0). 15 (60%) patients survived up to 24 weeks after the first dose.All patients experienced at least one adverse event(AE). Common AEs were leukopenia (12 patients), thrombopenia (9 patients), sepsis, anemia, TMA and hepatic dysfunction (6 patients). Among 10 death, causal relationship with JR-031 were not completely ruled out in 4 cases (TTP, pneumonia, sepsis and relapse of underlying malignancy), however there was no case in which the causality was strongly suggested.

Conclusion: It was suggested that JR-031 is a safe and effective therapy in the treatment of patients with SR-aGVHD.