Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy

Area of Science:

• Hematology
• Immunology
• Cell Therapy

Background:

• Mesenchymal stromal cells (MSCs) are explored for treating acute graft-versus-host disease (aGVHD).
• Long-term outcomes and immunologic effects of MSC therapy require further investigation.

Purpose of the Study:

• To identify predictors of outcome in patients receiving MSCs for aGVHD or hemorrhagic cystitis.
• To assess in vivo immunologic effects and long-term survival following MSC treatment.
• To evaluate the impact of MSC passage number on patient survival.

Main Methods:

• Retrospective analysis of 31 patients treated with MSCs between 2002-2007.
• Measurement of soluble IL-2 receptors, IL-6, and HLA-G levels pre- and post-MSC infusion.
• Correlation analysis of in vitro MSC suppression with clinical outcomes.
• Assessment of infectious complications, leukemia relapse, graft rejection, and survival rates.

Main Results:

• Soluble IL-2 receptor levels significantly declined post-MSC infusion (P = .03).
• Late infectious complications were common, with 54% of aGVHD survivors dying from infections between 4 months and 2 years post-treatment.
• Early-passage MSCs (passages 1-2) were associated with significantly higher 1-year survival (75%) compared to later-passage MSCs (passages 3-4) (21%) in GVHD patients (P < .01).
• Children had a better survival rate than adults (P = .005).

Conclusions:

• Treatment with early-passage MSCs improved survival in patients with therapy-resistant GVHD.
• While MSCs did not increase leukemia relapse, late infections pose a significant risk in treated patients.
• MSC passage number is a critical factor influencing treatment efficacy and patient survival.