Potential role of tracing stem cell transplantation and effects on the immune cell function of ferumoxytol combining with heparin and protamine in vivo/in vitro

2017 ◽  
Vol 41 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Jingyuan Zhao ◽  
Xin Guan ◽  
Yang Liu ◽  
Hua Piao ◽  
Rutao Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Potential Role ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function

Prophylactic infusion of cytomegalovirus-specific cytotoxic T lymphocytes stimulated with Ad5f35pp65 gene-modified dendritic cells after allogeneic hemopoietic stem cell transplantation

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 3974-3981 ◽  
Author(s):  
Kenneth P. Micklethwaite ◽  
Leighton Clancy ◽  
Upinder Sandher ◽  
Anna M. Hansen ◽  
Emily Blyth ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hemopoietic Stem Cell ◽  
Safety And Efficacy ◽  
Hemopoietic Stem Cell Transplantation

Abstract Cytomegalovirus (CMV) and its therapy continue to contribute to morbidity and mortality in hemopoietic stem cell transplantation (HSCT). Many studies have demonstrated the feasibility of in vitro generation of CMV-specific T cells for adoptive immunotherapy of CMV. Few clinical trials have been performed showing the safety and efficacy of this approach in vivo. In this study, donor-derived, CMV-specific T cells were generated for 12 adult HSCT patients by stimulation with dendritic cells transduced with an adenoviral vector encoding the CMV-pp65 protein. Patients received a prophylactic infusion of T cells after day 28 after HSCT. There were no infusion related adverse events. CMV DNAemia was detected in 4 patients after infusion but was of low level. No patient required CMV-specific pharmacotherapy. Immune reconstitution to CMV was demonstrated by enzyme linked immunospot assay in all recipients with rapid increases in predominantly CMV-pp65 directed immunity in 5. Rates of graft-versus-host disease, infection, and death were not increased compared with expected. These results add to the growing evidence of the safety and efficacy of immunotherapy of CMV in HSCT, supporting its more widespread use. This study was registered at www.anzctr.org.au as #ACTRN12605000213640.

The Genotype in the Donor and Recipient for the Polymorphim −174 G/C of the IL-6 Influences the Outcome of HLA-Identical Related Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4082-4082
Author(s):  
Carolina Martinez-Laperche ◽  
Victor Noriega ◽  
Adela Herraiz ◽  
A. Bosh ◽  
Beatriz Martin-Antonio ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Serum Levels ◽  
Mortality Rates ◽  
Haematopoietic Stem Cell ◽  
Kaplan Meier

Abstract Abstract 4082 Intoduction. Cytokine gene polymorphisms are well know to be associated with functional differences in cytokine regulation and altered clinical performance in a variety of diseases. They seem to play an important role in allogeneic stem cell transplantation (allo-SCT), mostly in the incidence and severity of graft-versus -host disease (GVHD) which is one of the most common serious complications of allo-SCT. Interleukin-6 (IL-6) is a proinflamatory cytokine known to be implicated in the pathogenesis of aGVHD with increasing serum levels during the development. The IL6−174 (G/C) single nucleotide polymorphism (SNP), localized in the promoter region (7p21) has been linked to in vitro and in vivo productions, associating the presence of allele G with significantly higher levels of IL-6 and a trend to have higher grades of aGVHD. Objetive. To analyze the influence of Donor (D) and Recipient (R) genotype for the polymorphism IL6−174 (G/C) on the outcome of HLA-identical related stem cell transplantation. Patients and Methods. The study comprised 171 allo-SCT (342 D/R samples) included in the Spanish Group for Haematopoietic Stem cell Transplantation (GETH) DNA bank. Genomic DNA was purified from peripheral blood samples obtained pre-SCT from patients and donors, after written informed consent. The IL6−174 (G/C) SNP genotype was determined by allele-specific PCR (Cavet et al, Blood 98, 2001). Results were analyzed using the Pearson's Chi-square Test and survival estimation by Kaplan-Meier curves. Results. Genotypes for D and R as well as D/R combinations (table 1), were in accordance with previous reports. Homozygous recipients for IL6−174GG polymorphism showed a trend to higher incidence of grade III-IV aGVHD than those with other genotypes (19.9% vs 9.1%) p=0.14. No significant differences were found in terms of cGHVD, relapse or mortality rates. On the other hand, patients transplanted from homozygous GG Donors showed a higher incidence of extense cGVHD (20/52 (38%) vs 21/87 (24%) p=0.07), lower relapse rates (10/59 (23.8%) vs 32/105 (76.2%) p=0.041) and better global mortality rates (23/62 (36.9%) vs 51/106 (69%) p=0.11). Survival analysis with Kaplan-Meier curves in this group of patients (IL6−174GG homozygotes in the Donor) revealed a lower cumulative incidence of relapse (CIR) (NR vs 567 days p=0.028) a better event free survival (EFS) (732 days vs 380 days p=0.02) and showed a trend to a better overall survival (OS) (1235 days vs 836 days p=0.157); (Figure1). Conclusions. IL6 cytokine is known to be implicated in the pathogenesis of aGHVD with increasing serum levels during its development. The presence of allele G for the polymorphism of IL6−174(G/C) which is associated with higher levels of IL6, has shown to influence the outcome of our cohort of HLA-identical related stem cell transplantation. Since acute GHVD is mainly influenced by R genotype and chronic GHVD by D genotype, the present study revealed that homocigous presence in the R of allele G was associated with higher incidence of aGHVD. Moreover when this allele is homozigously present in the D, patients show greater extense cGHVD and better EFS and OS. Genotyping for this polymorphism could aid in D selection or even more interestingly drive a risk-adapted management of transplanted patients. Disclosures: No relevant conflicts of interest to declare.

Azacytidine Compromises NK-Cell Activity in AML and MDS Patients Undergoing MRD-Based Pre-Emptive Treatment After Allogeneic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4122-4122
Author(s):  
Katja Sockel ◽  
Claudia Schönefeldt ◽  
Sieghart Sopper ◽  
Martin Wermke ◽  
Marc Schmitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Activating Receptors

Abstract Abstract 4122 The hypomethylating agent azacytidine (AZA) represents the standard treatment for many high-risk MDS and AML patients. While the clinical efficacy has been confirmed in several studies, the precise molecular mechanism of action has not been fully understood yet. Human NK-cells play an important role in the regulation of immune responses against malignant cells. Their function is controlled by a complex interplay of activating and inhibitory receptors - some of them being regulated by methylation of the respective genes. We, therefore explored, whether AZA modulates in vitro NK-cell function as well as in vivo during minimal-residual disease (MRD)-guided treatment of imminent relapse in MDS and AML patients treated within the prospective RELAZA trial (NCT00422890). Methods: After purifying NK-cells of healthy donors by MACS (magnetic cell sorting), NK-cells were exposed in vitro to different concentrations of AZA (100nM, 1μM, 3μM) with or without IL-2. In parallel, the NK-cell phenotype of patients (n=12) with AML or MDS, undergoing MRD-guided treatment with AZA after stem cell transplantation was monitored by FACS from peripheral blood samples on day 1, 5 and 7 of the first and second AZA cycle. All patients were still in complete haematological remission at the time of therapy. Results: In vitro, we observed a significant reduction (3,1% to 1,8% p=0.028) of the immature and cytokine-regulating CD56bright NK-cell subpopulation with increasing concentrations of AZA. There was a trend towards a reduced expression of the death-ligand TRAIL, the activating receptors NKG2D and NKp46 and for an increased expression of the inhibitory KIR CD158b1/b2, whereas we could not detect any changes in the expression of FAS-L, Perforin, Granzyme B, NKp30, NKp44, CD69, CD57, DNAM-1, CD16, and NKG2A-CD94. Confirmatory, we observed a significant decrease in the expression of TRAIL (p=0.003), NKG2D (p=0.03) and NKp46 (p=0.006) during AZA treatment in-vivo. Interestingly, these changes appeared to be reversible. The observed reduction of NK-cell activating receptors and TRAIL during AZA treatment correlated with a reduction or stable course of MRD in all analyzed patients. Conclusion: In summary these data suggest that the clinical effects of AZA are not mediated by enhancing NK-cell activity. In fact, the drug may have inhibitory effects on NK-cell function which should be considered when applying AZA in the post-transplant setting. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation

Blood ◽  
2001 ◽  
Vol 97 (3) ◽  
pp. 799-804 ◽  
Author(s):  
Carlijn Voermans ◽  
Marisha L. K. Kooi ◽  
Sjoerd Rodenhuis ◽  
Hans van der Lelie ◽  
C. Ellen van der Schoot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Migratory Capacity ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
Spontaneous Migration

Abstract To investigate whether the migratory ability of peripheral blood-derived CD34+ cells of patients undergoing autologous peripheral blood stem cell transplantation is related to the homing efficiency of these cells, the migration in vitro of these cells was determined and correlated with in vivo hematopoietic recovery. Large inter-individual differences of the in vitro migratory ability of the CD34+ cells were observed, ranging from 1.1% to 16.4% for spontaneous migration and 6.2% to 40.8% for SDF-1–induced (100 ng/mL) migration. Significantly faster hematologic recovery was observed in those patients who received transplanted CD34+cells that showed high spontaneous and SDF-1–induced migration in vitro (P < .05). Moreover, CD34+ cells from healthy G-CSF–mobilized donors exhibited significantly higher spontaneous and SDF-1–induced (P < .01) migration than CD34+ cells from patients mobilized with chemotherapy and G-CSF. The lower migratory capacity in vitro of patient-derived CD34+ cells was not due to lower expression of CXCR-4 but probably reflected decreased motogenic behavior of the cells. These results indicate that the migratory capacity of the cells is important for hematopoietic recovery. The data suggest that the engraftment potential of autologous stem cells is more or less impaired by treatment before or during the mobilization procedure and might possibly be restored by in vitro manipulation of the cells. In addition, an exponential relation between CXCR-4 expression and number of CD34+ cells that mobilized to the peripheral blood was found (P < .001), suggesting that CXCR-4 expression plays a role in the mobilization of CD34+ cells.

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