The Sensitivity and Specificity of 18F-Fluorodeoxyglucose Positron Emission Tomography -Computed Tomography for the Diagnosis and Monitoring of Acute Graft vs. Host Disease
Graft versus host disease (GVHD) is one of the major causes of death in patients undergoing
allogeneic hematopoietic cell transplantation (HCT). Despite prophylactic measures, the
incidence of acute GVHD is estimated at 40-60% among patients receiving allograft from
HLA-identical sibling donors, and may even reach 75% in patients receiving HLA-matched
unrelated grafts. Approximately 20% of the patients will develop the severe variant of the
disease and there is a tight association between the severity of GVHD and
transplantation-related-mortality. The treatment of GVHD is largely based on high dose
steroids regimen which is associated with long term morbidity and mortality. In the subgroup
of patients with steroid-refractory or slowly resolving GVHD, there are currently no
recommendations on the best timing of tapering down the steroids dose in the case of
resolution of the disease, or adding a second line medication, in case of non-resolving or
progression of the symptoms.
18F-FDG PET/CT (2-[fluorine-18] fluoro-2-deoxy-D-glucose, Positron emission tomography- CT)
is a noninvasive technique that allows quantifying and precisely localizing 18F-FDG uptake
in the entire body. 18F-FDG uptake is caused by increased local metabolic activity. Such
increased uptake has been described not only in neoplastic lesions but also in inflammatory
lesions (2). In this condition, uptake has been correlated with local stimulation of tumor
necrosis factor, and with monocyte priming and activation. A physiologic variable uptake may
be observed in the bowel, especially the cecum, and has limited the use of PET in
inflammatory bowel diseases. The advantage of combined PET and CT devices leads to
significant improvements in the interpretation of the bowel areas, and greatly reduces the
number of false-positive findings in the gastrointestinal tract.
CT-PET has been recently evaluated in our center as a diagnostic tool for Crohn disease. In
this study, CT-PET had a good correlation between FDG uptake and the severity of Crohn
disease. In the acute GVHD setting, a study reported on a small cohort suggested a
correlation between CT-PET findings, FDG uptake, and the diagnosis of lower gut acute GVHD.
In this study, we aim to evaluate and characterize the correlation between CT-PET findings
in patients suspected to have acute GVHD, and the disease course.
Observational Model: Cohort, Time Perspective: Prospective
Change of gut FDG uptake at onset and after treatment with steroids in patients with acute GVHD
CT-PET will be performed at the onset of GVHD(up-to 6 months from transplantation) and repeated after 4 weeks. The findings will be compared with the initial CT-PET results. The time frame of 4 weeks is the period of time in which most patients become either asymptomatic or in need for additional immunosuppressive therapy. In addition, all patients will go through the standard GVHD evaluation practice which includes (but not limited to) GI endoscopy (sigmoidoscopy and/or gastroscopy) and skin biopsies. Data obtained from the CT PET results will be compared with the GI findings.
At the onset of GVHD (up-to 6 months after hematopoietic cell transplantation) and then after 4 weeks from the date of first CT-PET (up-to 7 months after transplantation)
Ron Ram, M.D.
BMT Unit, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital
Israel: Ethics Commission