Mesenchymal Stem Cells for Treatment of Therapy-Resistant Graft-versus-Host Disease.
Ringden, Olle 1,2,5; Uzunel, Mehmet 1,2; Rasmusson, Ida 2; Remberger, Mats 1,2; Sundberg, Berit 1,2; Lonnies, Helena 1,2; Marschall, Hanns-Ulrich 3; Dlugosz, Aldona 3; Szakos, Attila 4; Hassan, Zuzana 1; Omazic, Brigitta 1,2; Aschan, Johan 1; Barkholt, Lisbeth 1; Le Blanc, Katarina 1,2
81(10):1390-1397, May 27, 2006.
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Background. Mesenchymal stem cells (MSC) have immunomodulatory effects. The aim was to study the effect of MSC infusion on graft-versus-host disease (GVHD).
Methods. We gave MSC to eight patients with steroid-refractory grades III-IV GVHD and one who had extensive chronic GVHD. The MSC dose was median 1.0 (range 0.7 to 9)x106/kg. No acute side-effects occurred after the MSC infusions. Six patients were treated once and three patients twice. Two patients received MSC from HLA-identical siblings, six from haplo-identical family donors and four from unrelated mismatched donors.
Results. Acute GVHD disappeared completely in six of eight patients. One of these developed cytomegalovirus gastroenteritis. Complete resolution was seen in gut (6), liver (1) and skin (1). Two died soon after MSC treatment with no obvious response. One of them had MSC donor DNA in the colon and a lymph node. Five patients are still alive between 2 months and 3 years after the transplantation. Their survival rate was significantly better than that of 16 patients with steroid-resistant biopsy-proven gastrointestinal GVHD, not treated with MSC during the same period (P=0.03). One patient treated for extensive chronic GVHD showed a transient response in the liver, but not in the skin and he died of Epstein-Barr virus lymphoma.
Conclusion. MSC is a very promising treatment for severe steroid-resistant acute GVHD.
(C) 2006 Lippincott Williams & Wilkins, Inc.