Selective Targeting of B Cells with Mesenchymal Stromal Cells Treatment Is An Efficacious Strategy for Cutaneous Cgvhd,

Cutaneous chronic graft versus host disease (cGVHD) is an increasingly common complication in long term survivors of hematopoietic stem cell transplantation, but currently available therapies have demonstrated limited efficacy. Furthermore, Mesenchymal Stromal Cells (MSCs) have been reported to be effective in various immune-mediated disease models, but their therapeutic potentials versus cutaneous cGVHD have not been determined.

We enrolled 23 patients suffering from cutaneous cGVHD who had failed to respond to conventional immunosuppressive therapy or relapsed after reduction of prednisone. They received intravenous in vitro expanded bone marrow (BM)-derived MSCs. The median follow-up period was 90 days (range 60–146 days).The dermal manifestations of cGVHD were monitored, and a score was given to the cutaneous response by the physician. B lymphocyte subsets and ratio of CD4/CD8 were detected by flow cytometry before the first and after the last MSC infusion. The plasmatic levels of TNF-α, sICAM-1 and Th1 or Th2 factors, including IL-2 and IL-4, were measured by enzyme-linked immunosorbent assay (ELISA).

Nineteen patients (82.61%) had skin symptom abatement after MSCs treatment with the skin scores improved according to the NIH criteria. Most patients had healing of skin ulceration, regression on skin findings and increased flexibility of involved joint. Steroid sparing or discontinuation of immunosuppressive medications was possible in all of the patients. Clinical improvement was accompanied by increasing levels of CD19⁺CD5⁺ B cells and elevated ratio of CD4/CD8. In addition, after the last MSCs treatment, the patients had significantly higher levels of IL-2 compared to before the first MSC infusion, while they had lower levels of TNF-α, sICAM-1 and IL-4.

MSCs infusion represents an effective treatment option for cutaneous chronic GVHD. This is of high interest in patients suffering from cutanous cGVHD resistant to conventional immunosuppressive therapy. MSCs alter allo-reactivity by affecting CD19⁺CD5⁺ B cells, possibly normalize the ratio of CD4/CD8 and Th1/Th2 and decreased the level of proinflammatory cytokine TNF-α and proadhesive cytokine sICAM-1. Our study demonstrates CD19⁺CD5⁺ B cells could be a possible target for therapeutic intervention in cutaneous cGVHD.

No relevant conflicts of interest to declare.