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Lisukov et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 9
doi: 10.3205/ctt-2010-No9-abstract02
© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "4th Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation",
Saint Petersburg, Russia, September 18–20, 2010

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Long-term outcomes of autologous stem sell transplantation in severe refractory systemic lupus erythematosus

Igor A. Lisukov1,3, Vera V. Sergeevicheva1, Svetlana A. Sizikova1, Alexander D. Kulagin1,3, Irina V. Kruchkova1, Andrey V. Gilevich1, Alexey E. Sizikov1, Lyudmila P. Konenkova1, Elena R. Chernykh1, Vladimir S. Kozhevnikov1, Tatyana N. Sentyakova2, Alexander A. Demin2, Boris V. Afanasyev3, Vladimir A. Kozlov1

1Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia; 2Novosibirsk State Medical University, Novosibirsk, Russia; 3St. Petersburg Pavlov State Medical University, St. Petersburg, Russia

Correspondence: Igor A. Lisukov, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., 199044, St. Petersburg, Russia; E-mail: igor_lisukov@spam is badmail.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. We report the results of a single-center study of ASCT in 15 patients (aged 18–55 years) with refractory to standard immunosuppressive treatment for systemic lupus erythematosus (SLE) in our Institution from 1998 to 2009.

Methods: Autologous hematopoietic stem cells 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=9). Pre-transplant conditioning regimens included BEAM (n=2), Melphalan 140 mg/m2 + Etoposid 1600 mg/m2 (n=2), Cy 200 mg/kg (n=3), Cy 200 mg/kg + ATG (n=2), and Cy 120 mg/kg (n=6). The control group included 15 female patients (aged 20–55 years) with refractory SLE on standard immunosuppressive treatment.

Results:
Three SLE patients died due to early transplant-related complications, and 12 patients achieved complete/partial remission (CR/PR). At a median follow- up of 51 ±10.,4 months, 5 patients were still in CR/PR. Seven patients (63.6%) had relapsed. Two patients had severe exacerbation (SLEDAI elevation on 12 points) and died at 7 and 8 years after ASCT.

Five patients developed mild exacerbation (SLEDAI elevation on 4–11 points). Five- year OS and RFS were 80% and 20%. In the control group (median follow-up 36±7.6 months) 5-year  OS was 70%, CR/PR was 0%, and disease related death was 20%.

Complete remissions observed in  SLE patients are accompanied by a disappearance of anti-ds DNA and ANA antibodies, increasing numbers of CD4+CD45RA+ T cells, CD4+CD25+bright T cells and CD4+Foxp3+ cells. We also demonstrated the significant increase of CD4+ and CD8+ T cells in S/G2M phase of the cell cycle until 1 year after ASCT. This data demonstrates that ASCT can induce the homeostatic proliferation of T cells and form the basis for immune reconstitution.

Conclusions: ASCT in refractory SLE patients can induce stable long-term remissions, however, the majority of patient’s relapses. The assessment of immune reconstitution can be important to understand the mechanisms of re-establishing self tolerance. International clinical trials would be required to clarify these questions. 

Keywords: SLE, stem cell transplantation, immune reconstitution

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