Signal Transduction and Targeted Therapy (Apr 2024)

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial

  • Yunfei Chen,
  • Yanmei Xu,
  • Ying Chi,
  • Ting Sun,
  • Yuchen Gao,
  • Xueqing Dou,
  • Zhibo Han,
  • Feng Xue,
  • Huiyuan Li,
  • Wei Liu,
  • Xiaofan Liu,
  • Huan Dong,
  • Rongfeng Fu,
  • Mankai Ju,
  • Xinyue Dai,
  • Wentian Wang,
  • Yueshen Ma,
  • Zhen Song,
  • Jundong Gu,
  • Wei Gong,
  • Renchi Yang,
  • Lei Zhang

DOI
https://doi.org/10.1038/s41392-024-01793-5
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 10

Abstract

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Abstract Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) present a promising alternative, capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders. This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP. The research design included administering UC-MSCs at escalating doses of 0.5 × 106 cells/kg, 1.0 × 106 cells/kg, and 2.0 × 106 cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase, followed by a dose of 2.0 × 106 cells/kg weekly for the dose-expansion phase. Adverse events, platelet counts, and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period. Ultimately, 12 (with an addition of three patients in the 2.0 × 106 cells/kg group due to dose-limiting toxicity) and six patients were enrolled in the dose-escalation and dose-expansion phase, respectively. Thirteen patients (13/18, 72.2%) experienced one or more treatment emergent adverse events. Serious adverse events occurred in four patients (4/18, 22.2%), including gastrointestinal hemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). The response rates were 41.7% in the dose-escalation phase (5/12, two received 1.0 × 106 cells/kg per week, and three received 2.0 × 106 cells/kg per week) and 50.0% (3/6) in the dose-expansion phase. The overall response rate was 44.4% (8/18) among all enrolled patients. To sum up, UC-MSCs are effective and well tolerated in treating refractory ITP (ClinicalTrials.gov ID: NCT04014166).