Use of mesenchymal stromal cells derived from the Wharton's jelly of human umbilical cord for treating patients with steroid-resistant graft versus host disease: predicting clinical response by a validated immunopotency assay.

Steroid-resistant (SR) graft-versus-host disease (GvHD) remains a severe complication following allogeneic hematopoietic progenitor cell transplantation (HPCT). Mesenchymal stromal cell (MSC)-based therapies hold promise but face challenges in demonstrating clinical efficacy. This study investigates how in vitro immunopotency, a critical quality attribute (CQA) of MSC, correlates with patient outcomes to inform MSC-based therapy development for SR-GvHD. In this retrospective descriptive case series study, we evaluated 49 patients (median age: 10 years, interquartile range, IQR: 5-17; 19 females, 30 males) treated for post-allogeneic HPCT acute (N = 40) and chronic (N = 9) SR-GvHD across 4 tertiary hospitals (2018-2022). Clinical-grade MSCs derived from the Wharton's jelly (MSC, WJ) of the umbilical cord of unrelated donors were administered compassionately at a target dose of 1 × 10⁶ MSC, WJ/kg for a median of 4 infusions at days 1, 4 and once weekly thereafter (197 total infusions). MSC were stratified by immunopotency (in vitro suppression of mixed-lymphocyte reactions: >70% vs. 30%-70%) using a validated assay. An overall response was achieved in 71.4% of patients at day 28 post-treatment (complete response in 11 patients), with 1-year survival of 55.1%. Overall survival in acute GvHD responders was significantly different (P = 0.012) than in the non-responding population. This was especially relevant in acute GvHD patients with improved overall survival in the population under 12 years (P = 0.039). Remarkably, higher in vitro immunopotency strength of MSC, WJ batches correlated with improved clinical responses in patients under 12 years (N = 28, P = 0.039). MSC, WJ therapy proved safe and effective for patients with SR-GvHD, with clinical response rates correlating significantly with measured immunopotency levels. These findings highlight the importance of defining meaningful CQAs and validated release criteria to ensure the therapeutic consistency of MSC-based products.