scholarly journals 337: The Predictive Value of Gene Expression Profiles for Acute Graft-Versus-Host Disease after Hematopoietic Cell Transplantation with Nonmyeloablative Conditioning for Hematological Malignancy

2008 ◽  
Vol 14 (2) ◽  
pp. 124
Author(s):  
T.N. Masmas ◽  
J.V. Johansen ◽  
L. Friis-Hansen ◽  
S.L. Petersen ◽  
B. Kornblit ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Predictive Value ◽  
Hematopoietic Cell Transplantation ◽  
Hematological Malignancy ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Graft Versus Host ◽  
Acute Graft

The Predictive Value of Gene Expression Profiles for Acute Graft-Versus-Host Disease after Hematopoietic Cell Transplantation with Nonmyeloablative Conditioning for Hematological Malignancy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1079-1079
Author(s):  
Tania N. Masmas ◽  
Lennart Friis-Hansen ◽  
Jens Vilstrup Johansen ◽  
Soren Lykke Petersen ◽  
Brian T. Kornblit ◽  
...  
Keyword(s):  
Gene Expression ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Late Onset ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Acute Graft

Abstract Purpose: To test the hypothesis that global gene expression profiles of peripheral blood mononuclear cells (PBMNC) day +14 after hematopoietic cell transplantation with nonmyeloablative conditioning could predict the later occurrence of acute graft-versus-host disease (GVHD) grade II–IV. Material: Between March 2000 and Marts 2006, 100 patients with hematological malignancies received peripheral blood stem cells from an human leukocyte antigen identical sibling/mother donor or from a matched unrelated donor following nonmyeloablative conditioning with low dose fludarabine and 2 Gy of total body irradiation. Post-transplant immunosuppression consisted of cyclosporine and mycophenolate mofetil. Only patients with sustained engraftment, who did not experience late-onset acute GVHD after day +100 were included; eight patients were excluded due to graft rejection, three patients due to suboptimal RNA or lacking PBMNC samples, and further 15 patients due to late-onset acute GVHD. Seventy-four patients were then eligible for microarray analysis. Methods: RNA was precipitated from frozen PBMNC from day +14 post-transplant and gene profiling analyses were performed using Human Genome U133 Plus 2.0 GeneChip Array. The array data were normalized, RMA modelled and asinh transformed in R. The differentially regulated gene expression between the group of patients developing acute GVHD before day +40, +56 and +84 post-transplant compared to the patients never experiencing acute GVHD was identified and formed the basis for the subsequent principal component analysis (PCA) and classifying models. No patients experienced acute GVHD between day +85 and +100 post-transplant. Results: The patients experiencing acute GVHD by different time points were separated from the patients never experiencing acute GVHD by the PCA plot. Furthermore the classifying models could separate the groups correctly in up to 93% of cases in the best of the classifying model. In addition, differentially regulated genes between the two groups were identified. Conclusion: These data suggest that the pattern of gene expression profiles early post-transplant is able to predict patients with a high risk of later occurrence of acute GVHD from those never experiencing acute GVHD. This knowledge could be exploited to increase the immunosupression and thus prevent acute GVHD in patients at risk. Furthermore, candidate genes of interest for the pathogenesis of acute GVHD have been identified.

Abstract 135: Endothelial Dysfunction in Acute Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation. In vitro Evidence of the Protective Effect of Defibrotide

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Enrique Mir ◽  
Marta Palomo ◽  
Enric Carreras ◽  
Maribel Diaz-Ricart ◽  
Montse Rovira ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Endothelial Damage ◽  
Hematopoietic Cell ◽  
Graft Versus Host ◽  
Acute Graft

Acute Graft-Versus-Host Disease (aGVHD) is the most common early complication after allogeneic Hematopoietic Cell Transplantation (allo-HCT). We demonstrated endothelial dysfunction (ED) in association with allo-HCT. According to this data, aGVHD has been linked to an inflammatory process that may affect the endothelium. To investigate the differential degree of endothelial damage in patients developing or not aGVHD, to identify potential biomarkers, and to explore the protective effect of defibrotide (DF) in this scenario. DF has orphan designation for GVHD prevention. Patients blood samples were collected before allo-HCT, at day 0, and every week till day 28 after HCT. Plasma proteins (sTNFR1, sVCAM-1, VWF and ADAMTS-13) were measured as biomarkers of ED in individual samples from patients developing (GVHD, n=24), or not (NoGVHD, n=13), aGVHD. In in vitro assays, endothelial cells (EC) in culture were exposed to media containing pooled sera from patients to evaluate changes in the: a) expression of VCAM-1 and ICAM-1 on cell surfaces; b) presence of VWF on the extracellular matrix (ECM) and c) reactivity of the ECM towards platelets, under flow. The effect of DF was explored in the in vitro experiments by previous exposure of the EC (for 24h) followed by continuous incubation (100 μg/ml, added every 24h). Levels of sTNFRI, sVCAM-1 and VWF in samples from group GVHD were significantly higher than in NoGVHD (increases of 100, 37 and 150% respectively, at diagnose, p<0.01). ADAMTS-13 activity and VWF levels were inversely related. In in vitro studies, cell surface expression of VCAM-1 and ICAM-1, presence of VWF and platelet adhesion on the ECM in response to GVHD samples were always superior (increases vs NoGVHD of 80, 40, 100 and 21%, respectively, at diagnose). In vitro exposure of EC to DF attenuated signs of endothelial injury reducing significantly (p<0.05) the expression of VCAM-1, ICAM-1 and VWF (reductions of 22, 30 and 30%, respectively) in the GVHD condition. Our results demonstrate endothelial damage in association with aGVHD, as evidenced by elevated plasma levels of several biomarkers. The in vitro approach showed a marked proinflammatory and prothrombotic phenotype in association with aGVHD, which could be significantly prevented by defibrotide.

Impact of Defibrotide in the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

2022 ◽  
pp. 106002802110681
Author(s):  
Rémi Tilmont ◽  
Ibrahim Yakoub-Agha ◽  
Nassima Ramdane ◽  
Micha Srour ◽  
Valérie Coiteux ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Control Group ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Background Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.

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