Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells

Abstract Mesenchymal stem cells (MSC) from adult bone marrow have the capacity to differentiate into several mesenchymal tissues and inhibit T-cell alloreactivity in vitro. Within the EBMT MSC expansion consortium we have used MSC to treat grades III–IV acute graft-versus-host disease (GvHD) in 40 patients. The MSC dose was median 1.0 (range 0.4–9) 10^6 cells/kg body weight of the recipient. No side-effects were seen after MSC infusions. Nineteen patients received one dose, 19 patients received two doses, two patients received three and five doses respectively. MSC donors were in five cases HLA-identical sibling donors, 19 haploidentical donors and 41 third-party HLA-mismatched donors. Among the 40 patients treated for severe acute GvHD, 19 had complete responses, nine showed improvement, seven patients did not respond, four had stable disease and one patient was not evaluated due to short follow-up. Twenty-one patients are alive between six weeks up to 3.5 years after transplantation. Nine of these patients have extensive chronic GvHD. One patient with ALL has recurrent leukaemia and one patient has denovo AML of recipient origin. We conclude that MSC have immunomodulatory and tissue repairing effects and should be further explored as treatment of severe acute GvHD in prospective randomized trials.

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Immunosupressive properties of human placenta-derived mesenchymal stem cells on control of acute graft-versus-host disease in mice.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.6547 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 6547-6547

Author(s):

M. J. Jang ◽

S. Y. Oh ◽

H. Kim ◽

H. Shin ◽

G. J. Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graft Versus Host Disease ◽

Human Placenta ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

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Adipose Tissue-Derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft-Versus-Host Disease

Stem Cells ◽

10.1634/stemcells.2006-0228 ◽

2006 ◽

Vol 24 (11) ◽

pp. 2582-2591 ◽

Cited By ~ 482

Author(s):

Rosa Yañez ◽

María Luisa Lamana ◽

Javier García-Castro ◽

Isabel Colmenero ◽

Manuel Ramírez ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Graft Versus Host Disease ◽

Host Disease ◽

Graft Versus Host

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Mesenchymal Stem Cells for Treatment of Severe Acute Graft-Versus-Host Disease.

Blood ◽

10.1182/blood.v108.11.2918.2918 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2918-2918 ◽

Cited By ~ 2

Author(s):

Katarina Le Blanc ◽

Francesco Frassoni ◽

Lynne Ball ◽

Edoardo Lanino ◽

Berit Sundberg ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Third Party ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

Abstract Mesenchymal stem cells (MSC) from adult bone marrow have the capacity to differentiate into several mesenchymal tissues and inhibit T-cell alloreactivity in vitro. Within the EBMT MSC expansion consortium we have used MSC to treat grades III-IV acute graft-versus-host disease (GvHD) in 40 patients. The MSC dose was median 1.0 (range 0.4–9) 10^6 cells/kg body weight of the recipient. No side-effects were seen after MSC infusions. Nineteen patients received one dose, 19 patients received two doses, two patients received three and five doses respectively. MSC donors were in five cases HLA-identical sibling donors, 19 haploidentical donors and 41 third-party HLA-mismatched donors. Among the 40 patients treated for severe acute GvHD, 21 had complete responses, eight showed improvement, eight patients did not respond, two had stable disease and one patient was not evaluated due to short follow-up. Twenty patients are alive between six weeks up to 3.5 years after transplantation. Nine of these patients have extensive chronic GvHD. One patient with ALL has recurrent leukaemia and one patient has denovo AML of recipient origin. We conclude that MSC have immunomodulatory and tissue repairing effects and should be further explored as treatment of severe acute GvHD in prospective randomized trials.

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