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Graft-versus-Host Disease

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

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 × 106/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.

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References

  1. Bacigalupo A . Management of acute graft-versus-host disease. Br J Haematol 2007; 137: 87–98.

    Article  CAS  PubMed  Google Scholar 

  2. Weisdorf D . GVHD—the nuts and bolts. Hematology Am Soc Hematol Educ Program 2007; 2007: 62–67.

    Article  Google Scholar 

  3. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.

    Article  CAS  PubMed  Google Scholar 

  4. Aggarwal S, Pittenger MF . Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815–1822.

    Article  CAS  PubMed  Google Scholar 

  5. Le Blanc K, Ringdén O . Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 2007; 262: 509–525.

    Article  CAS  PubMed  Google Scholar 

  6. Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J et al. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 2008; 22: 593–599.

    Article  CAS  PubMed  Google Scholar 

  7. Fang B, Song Y, Liao L, Zhang Y, Zhao RC . Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. Transplant Proc 2007; 39: 3358–3362.

    Article  CAS  PubMed  Google Scholar 

  8. Fang B, Song Y, Lin Q, Zhang Y, Cao Y, Zhao RC et al. Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft-vs-host disease in two children. Pediatr Transplant 2007; 11: 814–817.

    Article  CAS  PubMed  Google Scholar 

  9. Müller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F et al. Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis 2008; 40: 25–32.

    Article  PubMed  Google Scholar 

  10. Fang B, Song Y, Zhao RC, Han Q, Lin Q . Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis. Transplant Proc 2007; 39: 1710–1713.

    Article  CAS  PubMed  Google Scholar 

  11. Fang B, Song YP, Liao LM, Han Q, Zhao RC . Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells. Bone Marrow Transplant 2006; 38: 389–390.

    Article  CAS  PubMed  Google Scholar 

  12. Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006; 81: 1390–1397.

    Article  PubMed  Google Scholar 

  13. Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 2005; 11: 389–398.

    Article  PubMed  Google Scholar 

  14. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439–1441.

    Article  PubMed  Google Scholar 

  15. Lee ST, Jang JH, Cheong JW, Kim JS, Maemg HY, Hahn JS et al. Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype. Br J Haematol 2002; 118: 1128–1131.

    Article  PubMed  Google Scholar 

  16. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  17. Schallmoser K, Bartmann C, Rohde E, Reinisch A, Kashofer K, Stadelmeyer E et al. Human platelet lysate can replace fetal bovine serum for clinical scale expansion of functional mesenchymal stromal cells. Transfusion 2007; 47: 1436–1446.

    Article  CAS  PubMed  Google Scholar 

  18. Goedecke A, Richter K, Boxberger S, Wuschek N, Hoelig K, Bornhauser M . Differential effect of human and bovine serum sources on the proliferation and functional capacity of human mesenchymal stem cells. Exp Hematol 2007; 35 (9 Suppl1): 119.

    Google Scholar 

  19. NMDP guidelines to safeguard patients. http://www.marrow.org/PATIENT/Donor_Select_Tx_Process/The_Search_Process/NMDP_Guidelines_to_Safeguard_P/index.html#second.

  20. Sundin M, Ringdén O, Sundberg B, Nava S, Götherström C, Le Blanc K . No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 2007; 92: 1208–1215.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Centre for Regenerative Therapy Dresden (CRTD). MB and GE received additional support from the Deutsche Forschungsgemeinschaft (SFB 655; from cells to tissues).

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Correspondence to M Bornhäuser.

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Supplementary Information accompanies the paper on Bone Marrow Transplantation website (http://www.nature.com/bmt)

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von Bonin, M., Stölzel, F., Goedecke, A. et al. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43, 245–251 (2009). https://doi.org/10.1038/bmt.2008.316

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  • DOI: https://doi.org/10.1038/bmt.2008.316

Keywords

  • allogeneic hematopoietic stem cell transplantation
  • acute GVHD
  • MSC

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