Kontrastmittelunterstützte Sonographie nach allogener Stammzelltransplantation: Eine prospektive Pilotstudie (CEUS-Allo-2017)

The veno occlusive disease is a clinical syndrome that occurs predominantly as a compli-cation after hematopoietic stem cell transplantation. With a mortality rate of approxi-mately 80% in the untreated state, it is a serious complication and thus represents a clin-ical challenge. The current spectrum of diagnostic options consists of liver biopsy, clinical classification systems and imaging techniques such as B-scan sonography and color du-plex sonography. At the University Hospital of Marburg, Germany, a patient with clinical and sonographic evidence of the veno occlusive disease was found to have a so far undescribed hypoen-hancement of the liver compared to the spleen in a supplemental contrast ultrasonogra-phy. Therefore, the aim of this doctoral thesis was to verify these observations in contrast ultrasonography in a prospective pilot study and to investigate whether contrast ultraso-nography is suitable as a possible additional diagnostic method for the identification of the veno occlusive disease after hematopoietic stem cell transplantation. In this prospective pilot study, a selected group of 30 patients with a risk profile for the development of the veno occlusive disease was examined for the occurrence of pathologic contrast patterns by contrast ultrasonography at predefined points in time. It was shown that 21 patients had a pathological hypoenhancement of the entire liver compared to the spleen in the early phase after hematopoietic stem cell transplantation. This prospective pilot study was the first to objectify the subjective findings of the examiner. For this pur-pose, using the Quantity One® software, each patient's findings at the four points in time were examined for the percentage optical density of the liver compared to the spleen. According to contrast intensity quantification, a contrast intensity of the liver < 90% com-pared with the spleen after one minute was defined as a pathological hypoenhancement. Furthermore, it was observed that the condition of 17 of these 21 patients with a patho-logical hypoenhancement improved over time, even without therapy. Only one patient was clinically suspected of having a severe form of the veno occlusive disease. This pa-tient also showed both a subjective and objective pathological hypoenhancement of the entire liver after hematopoietic stem cell transplantation. Yet again, the patient’s condi-tion improved after successful therapy of the veno occlusive disease. Therefore, this doctoral thesis suggests that contrast ultrasonography may be suitable as an additional diagnostic method for the veno occlusive disease after hematopoietic stem cell transplantation. It has been shown that it is possible to detect the phenomenon of a hypoenhancement of the liver with a contrast ultrasonography even in a larger patient population. This phenomenon has so far only been observed in two case reports after hematopoietic stem cell transplantation. It should be stressed, however, that the patho-genesis of the pathological enhancement has not been finally clarified. Although an asso-ciation with the severity of the veno occlusive disease can be assumed, other causes such as drug toxic liver damage or other pathologies cannot be excluded and could only be clarified by histological confirmation. Moreover, it should be emphasized that contrast ultrasonography as a diagnostic method only offers added value in the identification of the veno occlusive disease when it is com-bined with the currently recognized diagnostic possibilities. These diagnostic possibilities comprise scoring systems like the Baltimore and Seattle criteria but also the criteria of the european blood and bone marrow transplant society as well as the sonographic Lassau criteria. However, these are only able to reliably diagnose severe forms of the veno oc-clusive disease. Within the scope of this doctoral thesis, evidence was found that suggests that contrast ultrasonography may be suitable for detecting both, severe and mild forms of the veno occlusive disease. In combination with the criteria of the european blood and bone marrow transplant soci-ety, contrast ultrasonography could thus offer a possibility to diagnose and therapize bor-derline cases of the veno occlusive disease more reliably. Due to the low potential for side effects, the value of contrast ultrasonography in identi-fying the veno occlusive disease should be investigated in further prospective studies and multicenter projects.