Treatment of Steroid Resistant GVHD by Infusion MSC
Condition: Graft-versus-host-disease
MeSH terms: Graft vs Host Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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
    

Intervention name(s): MSC (hPPL)
Intervention type(s): Biological
Intervention description(s): Treatment with MSCs (hPPL) is indicated as soon as steroid refractory acute GVHD is diagnosed
Other intervention name(s): Mesenchymal Stem Cells
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: MSC; GVHD; Adults; Children; steroid refractory acute GVHD occurring after allogeneic stem cell transplantation