Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial

 International Journal of Hematology, 15 July 2025

Background
Idiopathic pneumonia syndrome (IPS) is a rare but life-threatening complication following hematopoietic stem cell transplantation (HSCT), with high mortality rates and limited response to corticosteroids. Current treatment options remain insufficient, highlighting the need for new therapeutic approaches.

HLC-001 is an allogeneic umbilical cord-derived mesenchymal stromal cell (MSC) product manufactured under GMP standards, which has demonstrated anti-inflammatory and immunomodulatory effects in transplant-related lung diseases.

Study Design

• Type of study: Phase II, multicenter, single-arm, open-label trial.
• Sites: Seven hospitals in Japan.
• Participants: Seven patients with steroid-refractory or steroid-dependent IPS after HSCT (mean age 43.3 years; majority male).
• Treatment regimen: Intravenous infusion of HLC-001 at a dose of 2 × 10⁶ cells/kg, twice weekly, for up to 4 weeks.
• Primary endpoint: Overall survival at day 56.
• Secondary endpoints: Survival at day 100, reduction in steroid dose, improvement in respiratory function, chest imaging findings, Eastern Cooperative Oncology Group – Performance Status (ECOG-PS), and lung biomarkers.

Results

• Overall survival: 71.4% (5/7 patients) at day 56, maintained through day 100.
• Respiratory support: 6/7 patients did not require mechanical ventilation during follow-up.
• Steroid reduction: 83.3% (5/6 surviving patients) reduced prednisone dosage to <1 mg/kg/day.
• Imaging improvement: 60% of patients showed improvement on chest X-ray; 71% showed improvement on chest CT.
• Lung biomarkers (SP-D, KL-6): Downward trends in many patients, suggesting reduced lung injury.
• Safety: A total of 57 adverse events were reported among all patients, mostly mild to moderate, with no treatment-related deaths attributed to HLC-001.

Conclusion
HLC-001 demonstrated:

• Potential efficacy in improving survival rates in patients with severe IPS.
• Ability to reduce steroid requirements and support pulmonary recovery.
• An acceptable safety profile.

The authors recommend a phase III trial with a larger sample size and a control arm to confirm efficacy, along with long-term follow-up.

References

Doki, N., Fujii, N., Kako, S., Sakaida, E., & Kanda, Y. (2025). Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial. International Journal of Hematology, 1-11.

Source:  International Journal of Hematology

Link: https://link.springer.com/article/10.1007/s12185-025-04024-x#citeas