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: In this retrospective study, we review the immune reconstitution of children undergoing autologous hematopoietic stem cell transplantation. A total of 125 patients underwent autologous transplantation between 1992 and 2000. The report includes data on 58 patients. Data were not available on the remaining patients who either died before testing or data were not obtained. The parameters evaluated include: (a) immunophenotype by flow cytometry to quantify lymphocyte subpopulations (b) mitogen stimulation assays, and (c) quantitative immunoglobulins. The analysis reveals that CD3+ cells did not reach the normal range during the first year post-transplant. The median percentage of CD4+ cells was below normal up to 6 months post-transplant, while the absolute number remain low throughout the first year. The CD8+ percentage and absolute numbers remain normal at all times post-transplant. The CD19+ cells were also normal post-transplantation. The mitogen lymphocyte stimulation was normal in 27 out of 31 patients tested after 6 months post-transplant. Our analysis of immune reconstitution shows a similar pattern to previous studies with a faster recovery of the CD4/CD8 ratio, especially in those patients who did not receive TBI. In conclusion, the observed deficiencies are transient and have very little clinical significance because, historically, the rate of serious infections is low despite prolonged immune suppression. The recovery post-autologous transplant is fast.Bone Marrow Transplantation 03/2003; 31(4):285-90. · 3.54 Impact Factor
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ABSTRACT: The aim of this study was to investigate the mechanism underlying the effects of Astragalus membranaceus injection (AMI) on myelopoiesis in myelosuppressed mice. At 72 h after cyclophosphamide injection (250 mg/kg), the mice were administered AMI (500 mg/kg) intraperitoneally for 6 consecutive days or an equivalent volume of saline as a control. Murine colony-forming unit-fibroblast (CFU-F) formation, production of IL-6 and GM-CSF by bone marrow stromal cells (BMSC), and bcl-2 protein and mRNA expression in BMSC were measured by CFU-F assay, ELISA, immunohistochemistry and in situ hybridization. The results indicated that AMI improved the hematopoietic microenvironment by enhancing the BMSC survival and proliferation of CFU-F, production of IL-6 as well as GM-CSF by BMSC and bcl-2 protein and mRNA expression in BMSC, which promoted myelopoiesis. The data may provide a mechanistic basis for applying this ancient Chinese herb to promote hematopoiesis as an efficacious adjuvant therapy against myelosuppression induced by anti-cancer therapy.Phytotherapy Research 08/2007; 21(7):663-7. · 2.07 Impact Factor
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ABSTRACT: Growth factors are routinely used after autotransplantation to accelerate hematopoietic recovery, and are continued until the absolute neutrophil count (ANC) is >/=0.5 x 10(9)/l on 3 consecutive days. Since ANC often increases to very high levels with this strategy, we discontinued growth factor on the first day ANC reached 0.5 x 10(9)/l in 45 patients (Study Group), and compared their subsequent ANC to 108 historic controls who received growth factor longer. While ANC on the day after reaching 0.5 x 10(9)/l was comparable between groups, ANC on the third day was significantly higher in the Control Group (2.3 vs 4.9 x 10(9)/l; P=0.0003). When compared to the first day, ANC in the Study Group was higher by a median of 140% on the third day and by 450% in the Control Group (P=0.0002). A significantly higher proportion of patients experienced a decline in ANC after the first day in the Study Group. However, only one patient in the Study Group became neutropenic transiently and ANC recovered spontaneously the next day. The incidence of fever and hospitalization were comparable. We conclude that growth factors can be discontinued after autotransplantation the day the ANC reaches 0.5 x 10(9)/l, without compromising neutrophil recovery.Bone Marrow Transplantation 04/2004; 33(7):715-9. · 3.54 Impact Factor