RESUMO
We investigated dynamics of CD4+FOXP3+ T cell recovery following the high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients. Circulating CD4+FOXP3+ T cells of 79 MM patients were evaluated using flow cytometry before HDC with auto-HSCT, at the day of engraftment, and following 6 and 12 months. Percentage of CD4+FOXP3+ T cells restored rapidly following auto-HSCT, became higher than pre-transplant level at the day of engraftment and then subsequently decreased for a year. CD4+FOXP3+ T cells at the time of engraftment were increased in patients with the relapse or progression of MM during 12 months following auto-HSCT (n=10) compared to non-relapsed patients (n=50): 6.7% (5.3-8.9%) vs 4.9% (2.8-6.6%); PU = 0.026. Area under the curve was 0.72 (95% CI: 0.570-0.878; Ñ=0.026). Circulating CD4+FOXP3+ T cell count was not associated with the percentage of myeloma plasma cells in a bone marrow but depended on its amount in autografts. CONCLUSIONS: Relative count of CD4+FOXP3+ T cells restored rapidly following auto-HSCT (at the day of engraftment), became higher than pre-transplant level and then subsequently decreased for a year. Their excess at the time of engraftment is associated with early relapse.
RESUMO
Our objective was to evaluate the safety and clinical efficacy of autologous M2 macrophage transplantation in nonacute stroke patients. We also evaluated whether the intrathecal administration of macrophages influences the production of cytokines by peripheral blood cells and whether the levels of cytokines correlate with stroke severity and responsiveness to cell therapy. In this study, 13 patients (12 males and 1 female with a median age of 63 years) diagnosed with ischemic (n = 10) or hemorrhagic (n = 3) stroke were subjected to cell transplantation therapy (study group). On average, 21.9 × 10(6) autologous M2 macrophages were injected intrathecally. Thirteen matched case-control stroke patients who did not receive cell therapy comprised the control group. We did not observe any serious adverse events (i.e., intrahospital mortality, neurological worsening, and seizures) related to the cell injection. One patient in the study group and two patients in the control group died during the 6-month follow-up period due to recurrent stroke. In the study group, the NIHSS score decreased from 11 to 6 (p = 0.007) in 6 months after the therapy, whereas the patients in the control group showed a less pronounced neurological improvement (the NIHSS score decreased from 11 to 8, p = 0.07). The obvious positive response (the improvement of the NIHSS score ≥3) in the study group was observed in 75% versus 18% in the control group (pFET = 0.03). M2 cell introduction did not significantly affect the production of various cytokines. Nevertheless, pretreated levels of IL-8, IL-10, and IL-4 correlated with stroke severity. Moreover, responder patients had lower spontaneous production of IL-10, FGF-ß, PDGF, VEGF, and higher stimulation indexes of IL-1ß, TNF-α, IFN-γ, and IL-6 than nonresponders. These findings suggest that the intrathecal administration of autologous M2 cells in stroke patients is safe and leads to a better neurological recovery, which could be mediated through the immunomodulatory activity of M2 macrophages.
