A randomized study comparing the effect of GM-CSF and G-CSF on immune reconstitution after autologous bone marrow transplantation.
ABSTRACT Haemopoietic growth factors (HGFs) have been shown to accelerate recovery from severe neutropenia after autologous bone marrow transplantation (ABMT) but their effect on immune reconstitution is not well defined. The present study compares, through randomized trial, the in vivo effect of GM-CSF and G-CSF administration on the immune recovery of patients who underwent ABMT. For that purpose, we have sequentially analysed 14 different T, B and NK lymphoid cell subsets using appropriate dual staining during the first year following transplant (days +6, +17, +31, +66, +90, +120, +180, +360). 24 patients with lymphoproliferative disorders (20 lymphomas and four multiple myelomas) and who had undergone ABMT were included in the study. The median age was 43 years (range 22-62 years). All lymphoma patients were homogenously conditioned with BEAM. Our results show that both GM-CSF and G-CSF aid T-cell (CD3+/alpha beta) recovery though their contribution varies depending on the T-cell subset analysed. G-CSF contributed to a significantly faster recovery of CD8+ cells (P = 0.03). The CD8+ cell regeneration was produced mainly by activated cells (CD38+/HLA-DR+) which lacked the CD11b antigen. In contrast, GM-CSF favoured the regeneration of CD4+ cells (through both the CD45RO+ and CD45RA+ subset), leading to a higher CD4+:CD8+ ratio (P = 0.007). No statistically significant differences were detected in the three groups of patients as regards both the recovery of NK cells and NK activity. Furthermore, the use of HGF did not seem to exert a significant influence on the recovery of B lymphocytes. This recovery was based on the CD5+ subpopulation that showed a rapid rise after the first month. We suggest that G-CSF and GM-CSF not only influence myeloid recovery, but also regeneration of the immune system after ABMT.
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ABSTRACT: BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post-PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC-mediated immunohematopoietic recovery has yet to be determined.STUDY DESIGN AND METHODS: In a randomized evaluation, the effects produced by post-PBPCT G–CSF and GM–CSF on myeloid/lymphoid recovery and transplant outcome in women with chemosensitive cancer were compared. Thirty-seven ovarian cancer patients and 34 breast cancer patients ranging in age from 24 to 60 years were treated with carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and then randomly assigned to receive G–CSF (5 μg/kg subcutaneously) or GM–CSF (5 μg/kg subcutaneously) until Day 13 after PBPCT. Patients were compared in regard to hematopoietic recovery, posttransplant clinical management, and immune recovery. Finally, clinical outcome was estimated as time to progression and overall survival.RESULTS: Hematopoietic recovery and posttransplant clinical management were comparable in both the G–CSF and GM–CSF series. Conversely, significantly higher T-cell counts were observed in G–CSF-treated patients during the early and late posttransplant follow-up. Patients who received G–CSF showed a significantly longer median time to progression. A parallel analysis revealed that patients in whom a higher CD3+ count was recovered had a significantly longer overall survival and time to progression.CONCLUSION: The enhancement of post-PBPCT T-cell recovery observed in G–CSF-treated patients encourages the use of G–CSF to ameliorate immune recovery, which seems to play a role in post-PBPCT control of disease in cancer patients. GM–CSF might be administered to prolong immunosuppression after autologous PBPCT for autoimmune diseases or allogeneic PBPCT.Transfusion 11/2002; 41(12):1577 - 1585. · 3.57 Impact Factor
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ABSTRACT: A variety of T, B and natural killer (NK) cell subsets defined by surface markers were analyzed by double immunofluorescence flow cytometry in the peripheral blood of patients following autologous bone marrow transplantation (ABMT, n = 14), autologous peripheral blood stem cell transplantation (PBSCT, n = 10) and allogeneic bone marrow transplantation (allo-BMT, n = 6). Patients following ABMT were divided in 2 groups, those who did not received G-CSF post-transplant (ABMT, n = 6) and those who did (ABMT + G, n = 8). All patients following PBSCT or allo BMT received G-CSF. In all the groups prolonged significant decreases with respect to normal numbers were observed for the T CD3+, CD2+ and CD25+ subsets, more profound for the CD4+ subset but less for the CD8+ subset, especially following PBSCT (only decreased at 1 month). A significant expansion of the CD3+CD57+ and CD8+CD57+ phenotypes was noticed between 9 and 12 months following ABMT, the group of longer follow-up. Long-lasting expansion of the NK-like CD3+CD56+ and CD3+CD16+ subsets was also observed. The B CD19+ and CD20+ subsets had a significant overexpression from 4 months after ABMT, showing a normally balanced Igk+:Ig1+ ratio. Concordantly, the HLA-DR+ and HLA-DQ+ subsets showed significant increases. The NK CD56+ and CD16+ subsets had a faster recovery than the T or B subsets in all the groups. However, the CD3-CD56+, CD3-CD16+, CD16+CD56+, CD3-CD8+, and especially the CD3-CD57+, CD16+CD57+, and CD56+CD57+ subsets had a slower recovery than the global CD56+, CD16+, or CD57+ subsets. The biological and clinical implications of these findings are discussed.Hematology and Cell Therapy 12/1997; 39(6):301-6.
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ABSTRACT: Pretreatment with interleukin-1 (IL-1), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) can improve alveolar macrophage bactericidal activity against pneumococci. These effects vary in eusplenic and asplenic mice. Likewise, these cytokines have been shown to improve survival after an aerosol pneumococcal challenge. Mice dying in these studies had positive blood cultures and disseminated infection. The purpose of this study was to determine the effect of cytokine pretreatment on intravascular clearance of bacteria from eusplenic and asplenic mice. Two weeks after splenectomy or sham operation, mice were pretreated for various times with IL-1, G-CSF, or GM-CSF or their corresponding vehicles. Mice then received tail-vein injections of bacteria (0.1 mL), and quantitative blood cultures were performed 15 and 30 minutes thereafter. Splenectomized mice had impaired clearance of both pneumococci and Pseudomonas compared with sham-operated mice (p < 0.05). IL-1 enhanced clearance in splenectomized mice (p < 0.001) but not in sham-operated mice (p not significant). G-CSF enhanced bacterial clearance in sham-operated mice (p < 0.01) but not in splenectomized mice (p not significant). GM-CSF enhanced clearance in both groups (p < 0.001). The net effects of exogenous cytokine therapy for infections depends on the state of the host defenses at the time of therapy. These agents may be useful as adjuvants for the treatment of infections, but further study is warranted.The Journal of trauma 12/1997; 43(6):875-9. · 2.96 Impact Factor