Cord blood-derived mesenchymal stromal cells in children with steroid-dependent nephrotic syndrome: a prospective phase II study

Abstract Background Children with steroid-dependent nephrotic syndrome (SDNS) require long-term immunosuppressive (IS) treatment, significantly impacting their quality of life. Cord-blood-derived mesenchymal stromal cells (CB-MSCs) are multipotent stem cells with proven immunomodulatory properties. Methods We conducted an adaptive, open-label, single-arm, phase II trial with an adaptive second part to evaluate the efficacy of CB-MSCs in children aged 3–18 years with SDNS in remission for ≥ 6 months on IS therapy. In Part 1, patients received 3 intravenous infusions of CB-MSCs (1.5 × 10⁶/kg) at 1–2-week intervals, with rapid IS tapering and discontinuation after the third infusion. The primary endpoint was relapse-free survival at 6 months post-IS withdrawal, with a threshold of < 4/11 relapsing patients. In the adaptive Part 2, IS was discontinued before the first infusion to enhance CB-MSCs activity, and the dose was increased to 2 × 10⁶/kg, with a booster 4th infusion. A historical cohort of SDNS children tapering IS under standard care served as a post-hoc control. Results In Part 1, 9 patients were enrolled, and 7/9 (78%) relapsed, failing to meet the prespecified efficacy threshold. In Part 2, 11 patients were enrolled; 9 (82%) were in remission at 2 weeks post-third infusion and received the boosted dose. However, 6/11 (55%) relapsed within 6 months, with no significant difference in relapse-free survival compared to Part 1 (P = 0.25). Historical controls had significantly better relapse-free survival (P = 0.0007). Conclusion In children with SDNS, this novel therapy with CB-MSCs was safe but failed to improve relapse-free survival 6 months after IS withdrawal.