Treatment of Steroid Resistant GVHD by Infusion MSC
Treatment of Steroid Resistant GVHD by Infusion MSC
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
Inclusion Criteria:

 -  Newly diagnosed acute grade II-IV GVHD or chronic GVHD with an acute pattern matching
 grade II-IV after allogeneic stem cell transplantation

 -  Patients must have received 2 mg/kg/day of prednisolon for at least 3 consecutive days
 and experience progression of GVHD or no response to at least 7 days of steroid
 treatment.

 -  In addition to steroids the patient has received either cyclosporin

 -  Written informed consent

 -  MSC donor must be HIV, HTLV, hepatitis BS antigen, HCV and HBC, Treponema Pallidum
 antibody negative. MSC donors can be mismatched related donor, third party matched or
 mismatched donor.

 Exclusion Criteria:

 -  Patients with poor performance, not expected to survive 3 weeks.

 -  Donor Chimerism below 90%

 -  Active uncontrolled CMV, EBV or fungal infection