scholarly journals 18F-FDG-PET-MRI for the assessment of acute intestinal graft-versus-host-disease (GvHD)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wolfgang Roll ◽  
Philipp Schindler ◽  
Max Masthoff ◽  
Rebecca Strotmann ◽  
Jörn Albring ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Fdg Pet ◽  
Clinical Stage ◽  
Likert Scale ◽  
Clinical Severity ◽  
Clinical Staging ◽  
Host Disease ◽  
Graft Versus Host ◽  
Quantitative Pet ◽  
Intestinal Gvhd

Abstract Background Graft versus host disease (GvHD) is a frequent complication of allogeneic stem cell transplantation (alloSCT), significantly increasing mortality. Previous imaging studies focused on the assessment of intestinal GvHD with contrast-enhanced MRI/CT or 18F-FDG-PET imaging alone. The objective of this retrospective study was to elucidate the diagnostic value of a combined 18F-FDG-PET-MRI protocol in patients with acute intestinal GvHD. Methods Between 2/2015 and 8/2019, 21 patients with acute intestinal GvHD underwent 18F-FDG-PET-MRI. PET, MRI and PET-MRI datasets were independently reviewed. Readers assessed the number of affected segments of the lower gastrointestinal tract and the reliability of the diagnosis on a 5-point Likert scale and quantitative PET (SUVmax, SUVpeak, metabolic volume (MV)) and MRI parameter (wall thickness), were correlated to clinical staging of acute intestinal GvHD. Results The detection rate for acute intestinal GvHD was 56.8% for PET, 61.4% for MRI and 100% for PET-MRI. PET-MRI (median Likert-scale value: 5; range: 4–5) offers a significantly higher reliability of the diagnosis compared to PET (median: 4; range: 2–5; p = 0.01) and MRI alone (median: 4; range: 3–5; p = 0.03). The number of affected segments in PET-MRI (rs = 0.677; p <  0.001) and the MV (rs = 0.703; p <  0.001) correlated significantly with the clinical stage. SUVmax (rs = 0.345; p = 0.14), SUVpeak (rs = 0.276; p = 0.24) and wall thickening (rs = 0.174; p = 0.17) did not show a significant correlation to clinical stage. Conclusion 18F-FDG-PET-MRI allows for highly reliable assessment of acute intestinal GvHD and adds information indicating clinical severity.

Clinical molecular imaging in intestinal graft-versus-host disease: mapping of disease activity, prediction, and monitoring of treatment efficiency by positron emission tomography

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2909-2918 ◽  
Author(s):  
Matthias Stelljes ◽  
Sven Hermann ◽  
Jörn Albring ◽  
Gabriele Köhler ◽  
Markus Löffler ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Graft Versus Host Disease ◽  
Fdg Pet ◽  
Emission Tomography ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Intestinal Gvhd

Gastrointestinal graft-versus-host disease (GVHD) is a common and potentially life-threatening complication after allogeneic hematopoietic stem-cell transplantation (HSCT). Noninvasive tests for assessment of GVHD activity are desirable but lacking. In the present study, we were able to visualize intestinal GVHD-associated inflammation in an allogeneic murine transplantation model by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in vivo. A predominant localization of intestinal GVHD to the colon was verified by histology and fluorescence reflectance imaging of enhanced green fluorescent protein (EGFP)–expressing donor cells. Colonic infiltration by EGFP+ donor lymphocytes matched increased FDG uptake in PET examinations. These preclinical data were prospectively translated into 30 patients with suspected intestinal GVHD beyond 20 days after transplantation. A total of 14 of 17 patients with a diagnostic histology showed significant FDG uptake of the gut, again predominantly in the colon. No increased FDG uptake was detected in 13 patients without histologic evidence of intestinal GVHD. Our findings indicate that FDG-PET is a sensitive and specific noninvasive imaging technique to assess intestinal GVHD, map its localization, and predict and monitor treatment responsiveness. Novel targeted tracers for PET may provide new insights into the pathophysiology of GVHD and bear the potential to further improve GVHD diagnosis.

18F-FDG PET/CT in Graft Versus Host Disease–Associated Polymyositis

2020 ◽  
Vol 45 (2) ◽  
pp. e106-e107
Author(s):  
Apurva Sood ◽  
Alka Rani Khadwal ◽  
Tinu Lukose ◽  
Rajender Kumar ◽  
Harmandeep Singh ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Fdg Pet ◽  
Host Disease ◽  
Graft Versus Host ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

MyD88 in Donor Bone Marrow Cells Is Critical for Protection from Acute Intestinal Graft-Versus-Host Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1094-1094
Author(s):  
Ji Young Lim ◽  
Sung-Eun Lee ◽  
Yoo-Jin Kim ◽  
Gyeongsin Park ◽  
Eun Young Choi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Infiltration ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Infiltration ◽  
Donor Bone Marrow ◽  
Intestinal Gvhd

Abstract Allogeneic hematopoietic stem cell transplantation is an important therapeutic modality used to treat malignancies of hematopoietic origin, such as leukemia and lymphoma. However, development of graft-versus-host disease (GVHD) causes non-relapse mortality and substantial morbidity of recipients. Myeloid differentiation factor 88 (MyD88), a major adaptor mediating TLR signaling, is also known to deliver pro-inflammatory signals. Activation of inflammatory signaling through MyD88 plays a key role in the expansion of myeloid-derived suppressor cells (MDSC) which are a heterogeneous population of immature myeloid ells with anti-inflammatory activity. To explore the contribution of MyD88 expressed by donor bone marrow (BM) cells to development of GVHD, we induced GVHD using T-cell-depleted BM (TCD-BM) isolated from MyD88-deficient (MyD88KO) mice and T cells isolated from wild-type (WT) mice. We employed C57BL/6 (H-2b) → B6D2F1 (H-2b/d) mouse model of GVHD, which differ at major and minor histocompatibility loci. Lethally irradiated B6D2F1 recipient mice were transplanted with either T cell-depleted bone marrow (TCD BM, 5 x 106) from either WT or MyD88KO mice together with WT spleen T cells (1 x 106). Transplantation with MyD88KO TCD BM aggravated GVHD; serious gut damage was evident, with infiltration of T cells specifically into the intestines of recipients. GVHD hosts transplanted with MyD88KO TCD BM exhibited markedly reduced expansion of MDSC. GVHD aggravation after transplantation with MyD88KO TCD-BM, associated with high-level T cell infiltration into the intestine and insignificant expansion of MDSC, was reproduced in another minor histocompatibility mismatch model (C57BL/6 → BALB.B). We next examined allogeneic T cells in the spleens of GVHD hosts in terms of the expression levels of CCR9, which are known to be associated with T cell migration to the intestinal mucosa and the proportion of CCR9 positive cells in CFSE low CD8+ T cells was higher in recipients of MyD88KO TCD BM than WT controls. In parallel, the levels of CCL25 were more highly expressed in the gut of MyD88KO recipients than WT controls. Mixed leukocyte cultures of CFSE- labeled C57BL/6 T cells and irradiated B6DF1 feeder cells were prepared in the presence of MDSC isolated from MyD88KO or WT mice. T cells, co-incubated with MDSC isolated from MyD88KO BM, exhibited a greater extent of CFSE dilution and less Annexin V staining, compared to T cells co-incubated with cells from WT BM. Moreover, MDSC from recipients of MyD88KO TCD BM exhibited a reduced suppressive function, compared to their WT counterparts. Next, we determined whether insufficient expansion of and ineffective suppression by MDSC caused severe GVHD in recipients of MyD88KO TCD BM. Supplementation of transplanted mice with MDSC from WT mice, not from MyD88KO mice, attenuated the severity of GVHD and reduced intestinal T cell infiltration in recipients of MyD88KO TCD BM. To verify the importance of MyD88-mediated signaling by MDSC in protection against severe GVHD, we determined if transplantation with TCD-BM cells containing high levels of MDSC attenuated the severity of GVHD. Pre-treatment of BM donors with lipopolysaccharide increased the frequencies of MDSC and the amounts of MyD88 transcripts in TCD-BM transplant, and alleviated the severity of GVHD and intestinal T-cell infiltration. To explore whether MDSC expansion levels could be used to predict the severity of intestinal GVHD, the T/MDSC ratios were calculated in blood of patients at the time of engraftment and were significantly higher in patients with intestinal GVHD ≥ grade 2. In conclusion, we have shown that MyD88-dependent MDSC expansion from donor BM is critical for protection against fatal acute intestinal GVHD. Disclosures No relevant conflicts of interest to declare.

Clinical Severity Scores in Gastrointestinal Graft-Versus-Host Disease

2013 ◽  
pp. 1 ◽  
Author(s):  
Julie Abraham ◽  
Anne Janin ◽  
Jean-Marc Gornet ◽  
Régis Peffault de Latour ◽  
Marie Robin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Clinical Severity ◽  
Host Disease ◽  
Graft Versus Host ◽  
Severity Scores

Potential Involvement of Chemokine Fractalkine/CX3CL1 and CX3CR1high Monocytes in Chronic Graft Versus Host Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1815-1815
Author(s):  
Noriko Namba ◽  
Yoshio Katayama ◽  
Katsuji Shinagawa ◽  
Mitsune Tanimoto
Keyword(s):  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Immunosuppressive Agents ◽  
Basal Layer ◽  
Clinical Severity ◽  
Healthy Controls ◽  
Host Disease ◽  
Graft Versus Host ◽  
Positive Fraction ◽  
Cx3cr1 Expression

Abstract Chronic graft versus host disease (cGVHD) is the most common late complications of allogeneic stem cell transplantation (alloSCT). Pathogenesis of cGVHD is largely unknown. Immunosuppressive agents are widely used in management of cGVHD, but frequently with unfavorable control. For the establishment of better therapeutic strategy, it is important to determine the cell types that are responsible for cGVHD and the factors that play critical roles to recruit these cells into inflammatory sites. Fractalkine/CX3CL1 (FKN) is an unique chemokine that exists not only as a soluble chemoattractant but also as a membrane-anchored form to mediate firm adhesion of leukocytes, mainly monocytes/macrophages, via its cognitive receptor CX3CR1. Here, we report the potential involvement of FKN-CX3CR1 axis in cGVHD. First, we assessed CX3CR1 expression on peripheral blood CD14+ monocytes by flow cytometry. Peripheral blood samples were obtained from patients who had undergone alloSCT (8 men, 9 women; age: range 20–64, median 45; days after transplantation: range 97–2786, median 681). To assess the clinical severity of cGVHD, we generated a scoring system with a modification of “GVHD Morbidity Assessment” established for Long-term Follow-up Program in Fred Hutchinson Cancer Research Center. We noticed that CD14+ monocytes in patients without cGVHD displayed certain expression level of CX3CR1 (single peak in a histogram) similar to that in healthy controls, and much lower expression in patients with cGVHD. Statistically, the intensity of CX3CR1 expression on CD14+ monocytes showed strong inverse correlation with cGVHD score (n=17, p&lt;0.01, Spearman’s rank correlation coefficient). This was unlikely due to the internalization of this receptor by the binding of soluble FKN in the blood or the effect of immunosuppressive agents for the patients with severe clinical symptoms since the histogram of CX3CR1 in lymphocytes characterized by low forward and side scatter showed two distinct peaks (positive and negative fractions) and the intensity of positive fraction was similar in all patients and healthy controls with no significant correlation between cGVHD score and percentage of positive fraction. Next, we examined the expression of FKN in two cGVHD regions, 1) lungs obtained from patients who had undergone lung transplantation due to respiratory failure caused by bronchiolitis obliterans, and 2) skin, by immunohistochemical staining. FKN was strongly expressed on epithelium of bronchioles in cGVHD as well as in normal lungs. Obliterated bronchioles lost the FKN-positive epithelium and were replaced with fibrous tissues, sometimes extensively surrounded by CD14+ monocytes/macrophages. In normal skin, FKN was faintly expressed in the basal layer of epidermis. In contrast, in cGVHD patients, it was strongly expressed in epidermis where we observed a hyperproliferation of keratinocytes, known as a main FKN producer in the skin. Interestingly, dramatic infiltration of CD14+ monocytes/macrophages was observed in dermis in most patients, and sometimes even in epidermis, suggesting that CX3CR1high monocytes might be recruited from the circulation into dermis by the chemoattraction of FKN supplied by epidermis. Together, our study suggests that monocytes/macrophages, which can function as antigen presenting cells, may play a role in pathogenesis of cGVHD via the Fractalkine-CX3CR1 pathway, and highlights these cells and this chemokine-receptor axis as additional targets for cGVHD therapy.

scholarly journals Microbiome-intestine cross talk during acute graft-versus-host disease

Blood ◽  
2020 ◽  
Vol 136 (4) ◽  
pp. 401-409
Author(s):  
Hind Rafei ◽  
Robert R. Jenq
Keyword(s):  
Immune System ◽  
Graft Versus Host Disease ◽  
Hematologic Malignancies ◽  
Host Immune System ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Microbiome Research ◽  
Inflammatory State ◽  
Intestinal Gvhd

Abstract Allogeneic hematopoietic stem cell transplantation (allo-SCT) offers cure for a variety of conditions, in particular, but not limited to, hematologic malignancies. However, it can be associated with life-threatening complications, including graft-versus-host disease (GVHD) and infections, which are factors limiting its widespread use. Technical advances in the field of microbiome research have allowed for a better understanding of the microbial flora of the human intestine, as well as dissection of their interactions with the host immune system in allo-SCT and posttransplant complications. There is growing evidence that the commensal microbiome is frequently dysregulated following allo-SCT and that this dysbiosis can predispose to adverse clinical outcomes, especially including acute intestinal GVHD and reduced overall survival. In this review, we discuss the interactions between the microbiome and the components of the immune system that play a major role in the pathways leading to the inflammatory state of acute intestinal GVHD. We also discuss the microbiome-centered strategies that have been devised or are actively being investigated to improve the outcomes of allo-SCT patients in regard to acute intestinal GVHD.

Crypt loss is a marker of clinical severity of acute gastrointestinal graft-versus-host disease

2007 ◽  
Vol 82 (10) ◽  
pp. 881-886 ◽  
Author(s):  
Joshua Melson ◽  
Shriram Jakate ◽  
Henry Fung ◽  
Sally Arai ◽  
Ali Keshavarzian
Keyword(s):  
Graft Versus Host Disease ◽  
Clinical Severity ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Increased T-bet+ cytotoxic effectors and type I interferon–mediated processes in chronic graft-versus-host disease of the oral mucosa

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3620-3630 ◽  
Author(s):  
Matin M. Imanguli ◽  
William D. Swaim ◽  
Stacy C. League ◽  
Ronald E. Gress ◽  
Steven Z. Pavletic ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Graft Versus Host Disease ◽  
Type I Interferon ◽  
Clinical Severity ◽  
Effector Memory ◽  
Type I ◽  
Type I Ifn ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Although chronic graft-versus-host disease (cGVHD) is a major long-term complication of allogeneic hematopoietic stem cell transplantation, little is known of its pathogenesis. We have systematically examined oral mucosa among cGVHD patients and determined that the clinical severity of oral cGVHD was correlated with apoptotic epithelial cells, often found adjacent to infiltrating effector-memory T cells expressing markers of cytotoxicity and type I cytokine polarization. Accumulation of T-bet+ T-cell effectors was associated with both increased proliferation and the expression of the type I chemokine receptor CXCR3. Concurrently, in both infiltrating cells and keratinocytes, we observed increased expression of the CXCR3 ligand MIG (CXCL9) and interleukin-15 (IL-15), type I interferon (IFN)–inducible factors that support the migration, type I differentiation, and expansion of alloreactive effectors. In severely affected mucosa, we observed high levels of MxA, a protein specifically induced by type I IFN, and signal transducer and activator of transcription 1 (STAT1) phosphorylation, a critical step in the IFN-signaling pathway, along with increased numbers of plasmacytoid dendritic cells. These data challenge the current paradigm of cGVHD as a type II cytokine–driven disorder and support the model that oral cGVHD results from type I IFN–driven immigration, proliferation, and differentiation of T-bet+ type I T effectors. The clinical trials are registered at http://www.clinicaltrials.gov as NCT00331968.

scholarly journals Acute graft-versus-host disease associated cerebellitis as the cause of pyrexia of unknown origin detected with 18F-FDG-PET/CT

2021 ◽  
Vol 27 ◽  
pp. 100341
Author(s):  
Kerry E. Jewell ◽  
James A. Kuzich ◽  
Sze Ting Lee ◽  
Rebecca Trethowan ◽  
Richard Macdonell ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Fdg Pet ◽  
Unknown Origin ◽  
Host Disease ◽  
Graft Versus Host ◽  
Pyrexia Of Unknown Origin ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Acute Graft

scholarly journals 18 F-FDG PET/CT in Extensive Graft-Versus-Host Disease of the Gastrointestinal Tract Following Autologous Stem Cell Transplantation

Diagnostics ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 72 ◽  
Author(s):  
Danijela Dejanovic ◽  
Annemarie Amtoft ◽  
Annika Loft
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Fdg Pet ◽  
Whole Body ◽  
Host Disease ◽  
Graft Versus Host ◽  
Pet Ct ◽  
Fdg Pet Ct

Graft-versus-host-disease (GVHD) following stem cell transplantation (SCT) is a common complication in patients that have undergone allogenic SCT but rare in recipients of autologous SCT. Gastro-intestinal tract (GIT)-GVHD can be difficult to diagnose due to non-specific symptoms such as fever, nausea, diarrhea, and vomiting; a histological confirmation is therefore required. Here, we present the findings of a whole-body 18FDG PET/CT with extensive and multifocal involvement of the GIT in a patient that developed severe acute GVHD 93 days post autologous SCT for Hodgkin’s lymphoma. PET and CT findings included characteristic patterns of bowel inflammation with bowel wall thickening, mural stratification and enhancement with high FDG-uptake of the involved regions, as well as typical extra intestinal findings such as ascites, engorgement of the vasa recti and stranding of the mesenteric fat. Although, the above-mentioned findings are not exclusive to GIT-GVHD and can be seen in other settings of inflammatory bowel disease such as enterocolitis or Mb Crohn our findings were used for targeted biopsy that confirmed acute GIT-GVHD. This case demonstrates that 18F-FDG-PET/CT can be a valuable non-invasive tool in mapping the activity and distribution of intestinal GVHD and direct for targeted biopsies of involved regions.

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