The use of mesenchymal stem cells in therapy of steroid-resistance chronic refractory graft-versus-host disease after hematopoietic stem cell transplantation
DOI:
https://doi.org/10.12775/MBS.2014.026Keywords
chronic graft-versus-host disease, mesenchymal stem cells, childrenAbstract
Introduction. Chronic graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSC) are involved in tissue repair and modulating immune responses. We present report of two cases of use of third-party donor mesenchymal stem cells in the therapy of steroid-resistant chronic GVHD. Case reports. The doses of MSC in both patients were 1.08 and 1.4 x 106 cells per kg body weight respectively. Time from diagnosis of GVHD to infusion of MSC was 420 and 330 days, respectively. Both patients had single infusion of MSC. We did not observe any adverse effects after both infusions of MSC. We obtained initially a partial response and then complete response in the first patient and a partial response in the second patient. In the first patient we achieved improvement of skin involvement resulting in reduction of immunosuppression. In the second patient with scleroderma we achieved only a minor improvement. Conclusion. Administration of MSC is a safe method and might by an effective therapy for patients with chronic refractory GVHD.References
Ringden O, Deeg HJ: Clinical spectrum of graft-versus-host disease. In: Ferrara JLM, Deeg HJ, Burakoff S: Graft vs host disease, 2nd edn. Marcel Dekker, Inc: New York, 1996, pp 525-559.
Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB et al: Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267-276.
Flowers ME: Traditional treatment of chronic graft-versus-host disease. Blood Marrow Transplant Rev 2002; 12: 5-8.
Lee SJ, Vogelsang G, Flowers ME: Chronic graft-versus-host disease. Biol. Blood Marrow Transplant. 2003; 9: 215-233.
Ringden O, Uzunel M, Sundberg B, Lonnies L, Nava S, Gustafsson J, Henningsohn L, Le Blanc K: Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon. Leukemia 2007;21:2271-2276.
Bernardo ME, Cometa AM, Locatelli F: Mesenchymal stromal cells: A novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation? Bone Marrow Transplant 2012;47:323-329.
Sanchez-Guijo FM, Lopez-Villar O, Lopez-Anglada L, Villaron EM, Muntion S, Diez-Campelo M, Perez-Simon JA, San Miguel JF, Caballero D, Del Canizo MC: Allogeneic mesenchymal stem cell therapy for refractory cytopenias after hematopoietic stem cell transplantation. Transfusion 2012;52:1086-1091.
Hassan Z, Remberger M, Svenberg P, Elbander M, Omazic B, Mattsson J, Conrad R, Svahn BM, Ahlgren A, Sairafi D, Aschan J, Le Blanc K, Barkholt L, Ringden O: Hemorrhagic cystitis: A retrospective single-center survey. Clin Transplant 2007;21:659-667.
Ansari M, Strunk D, Schallmoser K, Delco C, Rougemont AL, Moll S, Villard J, Gumy-Pause F, Chalandon Y, Parvex P, Passweg J, Ozsahin H, Kindler V: Third-party mesenchymal stromal cell infusion is associated with a decrease in thrombotic microangiopathy symptoms observed post-hematopoietic stem cell transplantation. Pediatr Transplant 2012;16:131-136.
Aggarval S, Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005;105:1815-1822.
Le Blanc K, Ringden O: Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 2007;262:509-525.
Lazarus HM, Koc ON, Devine SM, Curtis 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.
Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M et al.: Treatment of severe acute graft-versus-host disease with third party haploidentical mesencgymal stem cells. Lancet 2004;363:1439-1441.
Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H et al: Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006;81:1390-1397.
Weng JY, Du X, Geng SX, Peng YW, Wang Z, Lu ZS et al: Mesenchymal stem cells as salvage treatment for refractory chronic GVHD. Bone Marrow Transplant 2010;45:1732-1740.
Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI: Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): Implications for therapeutic use. Bone Marrow Transplant 1995;16:557-564.
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I et al: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008;371:1579-1586.
Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW et al: Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant 2006;12:252-266.
Arora M, Burns LJ, Davies SM, Macmillan ML, Defor TE, Miller WJ et al: Chronic graft-versus-host disease : a prospective cohort study. Biol Blood Marrow Transplant 2003;9:38-45.
Weisdorf DJ: Chronic graft-versus-host disease: where is promise for the future? Leukemia 2005;19:1532-1535.
Gładysz D, Murzyn M, Czaplicka I, Olkowicz A, Oldak T, Mielcarek M, Kałwa K, Drabko K, Styczyński J, Pawelec K, Bruczkowski M, Baran J, Bruczkowski D: The first in Poland follow-up of 10 patients with steroid-refractory graft-versus-host disease treated with intravenously applied Wharton’s jelly-derived mesenchymal stem cells as a salvage therapy. Bone Marrow Transplant 2014;49(suppl 1) (abstract PH-AB232):S537.
Prevosto D, Zancolli M, Canevali P, Raffaella Zocchi M, Poggi A: Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 2007;92:881-888.
Dalloul A: CD5: A safeguard against autoimmunity and a shield for cancer cells. Autoimmun. Rev 2009;8:349-353.
Maccario R, Podesta M, Moretta A, Cometa A, Gomolo P, Montana D et al.: Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005;90:516-525.
Downloads
Published
How to Cite
Issue
Section
Stats
Number of views and downloads: 188
Number of citations: 0