Salvage Therapy Using Mesenchymal Stromal Cells “MSC-FFM” For a Severe Gastrointestinal Steroid-Refractory Acute Graft-Versus-Host Disease in a 12-Year-Old Boy with Sickle Cell Disease

Abstract

Acute Graft-versus-Host Disease (aGvHD) is a frequent complication after a Hematopoietic Stem Cell Transplantation (HSCT). Its gastrointestinal subtype is associated with a high mortality, especially in steroid-refractory cases. Managing Steroid-Refractory aGvHD (SR-aGvHD) remains challenging due to the lack of validated second-line immunosuppressive strategies. Mesenchymal Stromal Cells (MSCs) are a therapeutic option for SR-aGvHD, but its efficacy and clinical response in children varies. Two recent studies using pooled bone marrow mononuclear cells from multiple donors, MSC-FFM, have shown satisfactory overall response rates but the literature is still lacking in children.We report the case of a 12-year-old boy with severe sickle cell disease and exchange transfusion dependency, indicating HSCT. Following allogeneic related-donor HSCT, he developed grade IV, gastrointestinal SR-aGvHD with an unfavorable clinical outcome despite intensive treatment with mycophenolate mofetil, methylprednisolone, and ruxolitinib.After nine days of methylprednisolone, a weekly MSC-FFM treatment was initiated that led to partial resolution of the gastrointestinal symptoms at D+18 after the first infusion of MSC-FFM and transient complete clinical remission of the gastrointestinal SR-aGvHD at D+79. In summary, MSC-FFM infusion was well tolerated, leading to significant clinical improvement and transient complete clinical remission of severe gastrointestinal SR-aGvHD.