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Presentation Number: 690
Objectives. We previously reported the safety and efficacy of high-dose immune suppressive therapy and autologous peripheral blood stem cell transplantation (auto-PBSCT) for systemic sclerosis (SSc). In this study, to elucidate the mechanism of long-term efficacy, we analyzed the immune reconstitution after auto-PBSCT in patients with SSc.
Methods. Ten patients (2 male and 8 female) with SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilized during hematologic recovery after relatively high-dose CY (2 g/m2 for 2 days) followed by administration of granulocyte colony stimulating factor (G-CSF). After collecting PBSC more than 2x 10^6CD34+cells/kg by apheresis, CD34+ cells were immunologically selected and cryopreserved until PBSCT. All of the patients were treated with high-dose CY (50 mg/kg for 4 days) and auto-PBSCT. Immune reconstitution has been analyzed using lymphocyte immunophenotyping for 24 months. Serum levels of TNF-alfa, TGF-beta, and IL-6, intracellular IFN-gammma/IL-4 ratio in CD4+ T cells were measured before and after the treatment for 24 months.
Results. Improvement of skin sclerosis was sustained for 2 years. A titer of anti-Scl-70 was significantly decreased at 1-24 months. Number of CD8+ T cells recovered as fast as a month after auto-PBSCT and was increased at 6-24 months. Number of CD4+ T cell was severely suppressed at 1-6 months and was still less than 50% compared to that of baseline. Number of CD4+CD45RO+ T cells recovered earlier than those of CD4+CD45RA+ T cells. Recovery of CD4+CD25+ T cell was suppressed at 1-24 months. Number of B cells recovered to baseline at 12 months with low CD27+/CD27- ratio, suggesting decreased number of memory B cells. Serum levels of TNF-alfa, TGF-beta, IL-6 were elevated before the treatment and were decreased after the treatment. Intracellular IFN-gammma/IL-4 ratio in CD4 T cells was significantly increased at 1-24 months.
Conclusions. These observations suggest that high-dose CY with auto-PBSCT improves the disease activity of patients with SSc by suppressing CD4+ T cells and correction of cytokine imbalance.
Methods. Ten patients (2 male and 8 female) with SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilized during hematologic recovery after relatively high-dose CY (2 g/m2 for 2 days) followed by administration of granulocyte colony stimulating factor (G-CSF). After collecting PBSC more than 2x 10^6CD34+cells/kg by apheresis, CD34+ cells were immunologically selected and cryopreserved until PBSCT. All of the patients were treated with high-dose CY (50 mg/kg for 4 days) and auto-PBSCT. Immune reconstitution has been analyzed using lymphocyte immunophenotyping for 24 months. Serum levels of TNF-alfa, TGF-beta, and IL-6, intracellular IFN-gammma/IL-4 ratio in CD4+ T cells were measured before and after the treatment for 24 months.
Results. Improvement of skin sclerosis was sustained for 2 years. A titer of anti-Scl-70 was significantly decreased at 1-24 months. Number of CD8+ T cells recovered as fast as a month after auto-PBSCT and was increased at 6-24 months. Number of CD4+ T cell was severely suppressed at 1-6 months and was still less than 50% compared to that of baseline. Number of CD4+CD45RO+ T cells recovered earlier than those of CD4+CD45RA+ T cells. Recovery of CD4+CD25+ T cell was suppressed at 1-24 months. Number of B cells recovered to baseline at 12 months with low CD27+/CD27- ratio, suggesting decreased number of memory B cells. Serum levels of TNF-alfa, TGF-beta, IL-6 were elevated before the treatment and were decreased after the treatment. Intracellular IFN-gammma/IL-4 ratio in CD4 T cells was significantly increased at 1-24 months.
Conclusions. These observations suggest that high-dose CY with auto-PBSCT improves the disease activity of patients with SSc by suppressing CD4+ T cells and correction of cytokine imbalance.
H. Tsukamoto, None.