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<p>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 (<i>N</i> = 40) and chronic (<i>N</i> = 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: &gt;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 (<i>P</i> = 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 (<i>P</i> = 0.039). Remarkably, higher in vitro immunopotency strength of MSC, WJ batches correlated with improved clinical responses in patients under 12 years (<i>N</i> = 28, <i>P</i> = 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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Silvia Torrents,
  • Ana García-Buendía,
  • Margarita Codinach,
  • Luciano Rodríguez,
  • Júlia Marsal Ricomà,
  • Maria del Trabazo del Castillo,
  • Cristina Díaz de Heredia,
  • Maria Rosario Pérez-Torres Lobato,
  • Iván López Torija,
  • Alberto Mussetti,
  • Félix López Cadenas,
  • Marta Peña Domingo,
  • Nerea Castillo-Flores,
  • Sergi Querol,
  • Joaquim Vives

摘要

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.