Treatment of Steroid Resistant GVHD by Infusion MSC

Graft-versus-host-disease

MSC, GVHD, Adults, Children, steroid refractory acute GVHD occurring after allogeneic stem cell transplantation

For numerous malignant diseases allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy. One of the major complications is the occurrence of acute graft-versus-host-disease (aGVHD). Thirty to eighty percent of patients after HSCT develop aGVHD despite the prophylactic application of different immunosuppressive drugs. The response rates to the conventional first line treatment are only 15-35%4. In case of a steroid refractory aGVHD different therapeutic strategies have been evaluated, but with no satisfactory results so far. The mortality of patients suffering from steroid refractory aGVHD remains at 75-80%. Therefore, it remains important to search for new therapeutical strategies for the treatment of aGVHD.

For numerous malignant and non-malignant hematological diseases allogeneic hemato¬poietic stem cell transplantation (HSCT) is the only curative therapy. One of the major complications is the occurrence of acute graft-versus-host-disease (aGVHD). Thirty to eighty percent of patients after HSCT develop aGVHD despite the prophylactic application of different immunosuppressive drugs depending on risk factors such as HLA-match, donor relation, age etc.1-3. First line therapy of aGVHD \> grade I consists of steroids at a dose of 2 mg/kg. The response rates to this treatment are only 15-35%4. In case of a steroid refractory aGVHD different therapeutic strategies have been evaluated, but with no satisfactory results so far. The mortality of patients suffering from steroid refractory aGVHD remains at 75-80%, although numerous studies with different treatment strategies have been conducted2-5. Therefore, it remains important to search for new therapeutical strategies for the treatment of aGVHD. The first patient to receive mismatched Mesenchymal Stem Cells was a twenty-year-old woman with acute myeloid leukemia treated with peripheral blood stem cells combined with MSC from her haploidentical father. Lazarus et al. reported on 46 patients who received HSCs and culture-expanded MSCs from HLA-identical siblings. Moderate to severe acute GvHD was observed in 28% of the patients, and chronic GvHD was seen in 61%. The two-year progression-free survival was observed in 53% of the patients. MSC infusion caused no acute or long-term MSC-associated adverse events. Traditionally, for MSC isolation and expansion, fetal calf serum (FCS) supplemented media are used. The use of FCS has however several drawbacks and potential problems. We have therefore established a MSC culture protocol in animal serum free conditions using human platelet lysate and human plasma instead. The present phase I/II study is designed to gather further insight into the clinical benefit in 50 patients (adults and children) with GvHD exerted by MSC expanded with human platelet lysate and plasma

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