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Co-infusion of MSCs during HSCT for GvHD prophylaxis
By Ella Dixon
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Although allo-HCT offers potential curative treatment for several hematologic disorders, aGvHD and cGvHD are common.1 aGvHD occurs in up to 60% of allo-HCT recipients despite standard prophylaxis; and is more common in patients with donor/recipient HLA disparities. First-line therapy with high-dose corticosteroids only has a ≤50% response rate, including partial responses. In previous clinical trials, MSCs have been shown to be effective in treating aGvHD when administered after HSCT, with inconsistent findings for GvHD prophylaxis.1 A prospective, double-blind, randomized phase II trial (NCT01045382) examined the co-infusion of MSCs during HSCT from HLA-mismatched donors (N = 38; placebo, n = 15; MSC, n = 23).1 It aimed to reduce GvHD incidence and/or severity and improve outcomes in patients receiving reduced-intensity conditioning. Results were published by Lombardo et al.1 in Stem Cell Research & Therapy. |
| Key learnings |
| The 1-year OS was 80% with placebo vs 74% with MSCs, with a 5-year OS of 58% vs 44%. No significant differences in OS, PFS, or relapse were observed at Years 1 or 5. |
| MSC treatment significantly reduced the incidence of Grade II–IV aGvHD at Day 100 (p = 0.0284) independent of the effect of ATG, which significantly reduced the overall risk of cGvHD (p = 0.0234). |
| MSC infusion was well tolerated with no acute toxicity. The rates of infections and secondary malignancies were comparable to the placebo group. MSCs offer a good safety profile compared to alternative immunosuppressive treatments. |
| GvHD remains a critical post-transplant challenge; therefore, further trials are warranted to confirm efficacy, optimize MSC dosing, and compare outcomes with alternative GvHD prophylaxis strategies, such as PTCy or abatacept. |
Abbreviations: aGvHD, acute graft-versus-host disease; allo-HCT, allogeneic hematopoietic cell transplantation; ATG, antithymocyte globulin; cGvHD, chronic graft-versus-host disease; GvHD, graft-versus-host disease; HLA, human leukocyte antigen; HSCT, hematopoietic stem cell transplantation; MSC, mesenchymal stromal cell; OS, overall survival; PTCy, post-transplant cyclophosphamide.
- Lombardo G, Lechanteur C, Briquet A, et al. Co-infusion of mesenchymal stromal cells to prevent GVHD after allogeneic hematopoietic cell transplantation from HLA-mismatched unrelated donors after reduced-intensity conditioning: a double-blind randomized study and literature review. Stem Cell Res Ther. 2024;15(1):461. DOI: 1186/s13287-024-04064-w
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