Treatment of familial hemophagocytic lymphohistiocytosis with third-party mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) represent an attractive tool for cellular therapies on grounds of their immunomodulatory and regenerative properties. Here, we report the first case of familial hemophagocytic lymphohistiocytosis (FHL) treated with MSCs. This rare autosomal recessive disorder is characterized by hyperinflammation that results from a failure of natural control mechanisms to terminate immune responses. Crosstalk between innate (macrophages) and adaptive (T cells) immunity is heavily altered. Immunochemotherapy is only temporarily effective in the control of FHL, and the outcome is usually fatal unless the patient undergoes allogeneic stem cell transplantation. Our hypothesis was that the application of MSCs could be effective in the treatment of FHL, since MSCs possess a broad repertoire of immunomodulating mechanisms impacting both innate and adaptive immunity pathways. In fact, the adoptive transfer of third-party MSCs transiently controlled the extreme immunological deterioration in the described patient who was otherwise not responsive to standard treatment, including repetitive chemotherapy. If these transient effects of MSCs can be confirmed in future-controlled clinical trials, adoptive MSC therapy could represent a salvage agent in FHL acting as a bridge to definitive treatment with stem cell transplantation.