Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium

Bone Marrow Transplant. 2009 Feb;43(3):245-51. doi: 10.1038/bmt.2008.316. Epub 2008 Sep 29.

Abstract

Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They have been used in patients with steroid-refractory acute GVHD (aGVHD), but their relevance as a therapeutic agent targeting aGVHD has still to be defined. In this case series, we report 13 patients with steroid-refractory aGVHD who received BM-derived MSC expanded in platelet lysate-containing medium from unrelated HLA disparate donors. MSC were characterized by their morphological, phenotypical and functional properties. All tested preparations suppressed the proliferation of in vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 x 10(6)/kg (range 0.6-1.1). The median number of MSC applications was 2 (range 1-5). Only two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days, five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment. In our patient cohort, response to MSC transfusion was lower than in the series reported earlier. However, our experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Blood Platelets / chemistry
  • Blood Platelets / physiology*
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / therapy*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Activation
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Middle Aged
  • Treatment Outcome

Substances

  • Immunosuppressive Agents