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

Bone Marrow Transplantation volume 38, pages 389–390 (2006)Cite this article

Severe graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (ASCT), and a number of approaches are therefore being evaluated.1, 2, 3, 4, 5 Recently, Le Blanc et al.6 reported a case of grade IV therapy-resistant acute GVHD of the gut and liver that showed rapid improvement after infusion of mesenchymal stem cells (MSCs). We here report a pilot study using human adipose tissue-derived MSC (AMSC) to treat severe acute GVHD after ASCT.

A 38-year-old female with acute lymphocytic leukemia in second remission received a transplant of hematopoietic stem cells (HSCs) from a human lymphocyte antigen (HLA)-identical unrelated female donor after conditioning with Ara-C (4 g/m2/day) intravenously (i.v.) on days −10 to −9; busulfan (4 mg/kg/day) orally on days −8 to −6; cyclophosphamide (1.8 g/m2/day) i.v. on days −5 to −4; Me-CCNU (250 mg/m2) orally once on day −3. Immunosuppression included ATG (thymoglobulin, 2.5 mg/kg/day; Sang Stat, Lyon, France) i.v. for 4 consecutive days, on days −5 to −2 during the conditioning, followed by a combination of cyclosporine A (CsA), a short course of mycophenolate mofetil (MMF) and four doses of methotrexate (MTX). On day +21, the patient developed a maculopapular rash of the thorax and back that progressed despite treatment with prednisolone (2 mg/kg/day). On day +38, the patient developed severe diarrhea (>1200 ml/day) and abdominal pain requiring morphine, and then she stopped eating and was treated with total parenteral nutrition (TPN). Colonoscopy showed moderate-to-severe acute GVHD. The serum total bilirubin level exceeded 230 μmol/l, and serum alanine aminotransferase (ALT) concentration was higher than 400 U/l. Extracorporeal psoralen-enhanced UVA light treatment (three times per week) was tried for 6 weeks. Methylprednisolone (500 mg/day), infliximab (10 mg/kg) and daclizumab (1 mg/kg) were ineffective. MMF, tacrolimus and MTX were also tried. Colonoscopy on day +62 showed grade IV GVHD. In conclusion, this patient seemed to be unresponsive to all types of immunosuppression. At the same time, she was treated for repeated bacterial, viral and invasive fungal infections.

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Authors and Affiliations

  1. Henan Tumor Research Institute, Henan Tumor Hospital, Henan Medical School, Henan University, Zhengzhou, China

    B Fang & Y P Song

  2. Institute of Haematology and Blood Diseases Hospital, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Tianjin, China

    L M liao, Q Han & R C Zhao

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  1. B Fang
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Fang, B., Song, Y., liao, L. et al. Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells. Bone Marrow Transplant 38, 389–390 (2006). https://doi.org/10.1038/sj.bmt.1705457

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