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ctt-journal > Lisukov et al. (Abstract)

Lisukov et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 2, No. 5, 2009
doi: 10.3205/ctt-2009-No5-abstract15
© The Authors. This abstract is provided under the following license:
Creative Commons Attribution 3.0 Unported


Abstract accepted for "Joint EBMT Pediatric Working Party – 3rd Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation", Saint Petersburg, Russia, September 17–20, 2009

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Immunoablation followed by autologous stem cell transplantation in refractory autoimmune diseases: clinical outcomes and immune reconstitution

Igor A. Lisukov1,2, Vera V. Sergeevicheva2, Svetlana A. Sizikova2, Alexander D. Kulagin1,2, Irina V. Kruchkova2, Andrey V. Gilevich2, Alexey E. Sizikov2, Lyudmila P. Konenkova2, Elena R. Chernykh2, Vladimir S. Kozhevnikov2, Alexander A. Demin1, Vladimir A. Kozlov2

1Novosibirsk State Medical University, Novosibirsk, Russia; 2Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia

Correspondence: Alexander D. Kulagin, Institute of Clinical Immunology SB RAMS, Yadrintsevskaya str, 14, 630047, Novosibirsk, Russia, E-mail: kulagingem@rambler.ru

Abstract

High-dose immunosuppression and autologous hemopoietic stem cell transplantation (ASCT) has been proposed as an investigational therapy for patients with refractory autoimmune diseases (AD). We report the results of a single-center study of ASCT in 15 patients with refractory systemic lupus erythematosus (SLE), 7 patients with progressive multiple sclerosis (MS), 1 patient with autoimmune thrombocytopenia (ITP) relapsed after splenectomy, and 1 patient with pure red cell aplasia (PRCA) in our institution from 1998 to 2009.

Methods: Autologous HSC were collected from bone marrow (n=4) or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) (n=2) or Cy and G-CSF (n=18).

Results: Three SLE patients died due to transplant-related complications, 1 MS patient died due to t-AML 4 years after ASCT, 2 SLE and 1 PRCA patients died after 8, 7 and 2 years respectively due to relapses. At a median follow up of 54 (16–124) months 7 patients are in complete remission (4 SLE, 2 MS, 1 ITP). Three MS patients are in a stabilization phase, while 1 MS patient relapsed 5 years after ASCT. CR observed in SLE patients is accompanied by a disappearance of anti–ds DNA and ANA antibodies and an increasing number of CD4+CD45RA+ T cells, CD4+CD25+bright T cells and CD4+Foxp3+ cells. We also demonstrated the increase of CD4+ and CD8+ T cells in the S/G2M phase of the cell cycle until1 year after ASCT.

Conclusion:
ASCT in refractory AD can induce stable long-term remissions; however, the majority of patients relapse. The assessment of immune reconstitution can be important to understanding the mechanisms of self-tolerance re-establishment. International clinical trials would be required to clarify these questions. 

Keywords: immunosuppression, autologous hematopoietic stem cell transplantation, lupus erythematosus, multiple sclerosis, autoimmune thrombocytopenia

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