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Early modifications of the gut microbiome in children with hepatic sinusoidal obstruction syndrome after hematopoietic stem cell transplantation
Masetti, R., Biagi, E., Zama, D., Muratore, E., D'Amico, F., Leardini, D., Turroni, S., Prete, A., Brigidi, P., Pession, A.
Scientific reports. 2021;11(1):14307
Abstract
Hepatic sinusoidal obstruction syndrome (SOS/VOD) represents a dramatic complication of hematopoietic stem cell transplantation (HSCT), particularly in children. Recent evidence has suggested a role for the gut microbiome (GM) in the context of HSCT and its related complications, but no data are available on the relationship between GM and SOS/VOD. Here, we conducted a retrospective case-control study in allo-HSCT pediatric patients developing or not SOS/VOD and profiled their GM over time, from before the transplant up to 72 days after. A rich and diverse GM before HSCT was found to be associated with a reduced likelihood of developing SOS/VOD. Furthermore, prior to transplant, patients not developing SOS/VOD showed an enrichment in some typically health-associated commensals, such as Bacteroides, Ruminococcaceae and Lachnospiraceae. Their levels remained overall higher until post-transplant. This high-diversity configuration resembles that described in other studies for other HSCT-related complications, including graft-versus-host disease, potentially representing a common protective GM feature against HSCT complications.
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Veno-occlusive Disease in HSCT Patients: Consensus-based Recommendations for Risk Assessment, Diagnosis, and Management by the GITMO Group
Bonifazi, F., Sica, S., Angeletti, A., Marktel, S., Prete, A., Iori, A. P., Olivari, D., Rossetti, G., Bertaina, A., Botti, S., et al
Transplantation. 2020
Abstract
Variation in clinical practice affects veno-occlusive disease (VOD) management, mainly in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT). Disputes about diagnostic criteria, treatment and prophylaxis, due to the lack of high-quality data, are at the base of this variability. With the aim of limiting inconsistency in clinical care, thus improving both patient outcomes and data collection reliability, the Italian Society of Stem cell transplant (GITMO) launched a collaborative effort to formulate recommendations based on integration of available evidence and expert's consensus. A systematic method, according to US National Institute of Health (NIH) guidelines and Italian National System for Guidelines, was used. Twenty-nine recommendations were approved with a strong (20) or weak (9) level of agreement, while 26 were rejected. In particular, the Panel pointed out the need to achieve an early diagnosis, encouraging the adoption of EBMT criteria and the prompt use of ultrasonography. Moreover, our experts strongly recommended in favour of prophylactic use of ursodeoxicolic acid (UDCA). As soon as a VOD diagnosis is established, treatment with defibrotide should be started for at least 21d. A number of areas of uncertainty, particularly concerning risk stratification and use of diagnostic tools such as elastography has been identified and discussed.
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SINUSOIDAL OBSTRUCTION SYNDROME / VENO-OCCLUSIVE DISEASE AFTER AUTOLOGOUS OR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN: a retrospective study of the AIEOP-HSCT (Italian Hematology-Oncology Association-Hematopoietic Stem Cell transplantation) Group
Faraci, M., Bertaina, A., Luksch, R., Calore, E., Lanino, E., Saglio, F., Prete, A., Menconi, M. C., De Simone, G., Tintori, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
INTRODUCTION Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a large cohort of children transplanted in centers across Italy applying the new EBMT criteria, and to analyze the risk factors underlying this complication. MATERIALS AND METHODS We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP-affiliated centers between January, 2000 and April, 2016. The new pediatric EBMT criteria were retrospectively applied for diagnoses of SOS/VOD and severity grading. RESULTS Among 5,072 transplants considered at risk for SOS/VOD during the study period, 103 children (2%) developed SOS/VOD and the grade was severe or very severe in all patients. The median time of SOS/VOD occurrence was 17 days after HSCT (range 1-104 days). Sixty-nine patients (67%) were treated with Defibrotide (DF) for a median time of 16 days (range 4-104). In multivariable analysis, age <2 years, use of busulfan during the conditioning regimen, female gender and hemophagocytic lymphohistiocytosis were risk factors statistically associated with the development of SOS/VOD. The overall mortality directly related to SOS/VOD was 15.5%. Overall survival (OS) at 1 year was worse in patients with SOS/VOD (p=0.0033), and this difference disappeared 5 years after HSCT. Non-relapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (p<0.001). CONCLUSION Based on the application of new EBMT criteria, the overall incidence of SOS/VOD recorded in this large Italian pediatric retrospective study was 2%. Non-relapse mortality was significantly higher in patients who developed SOS/VOD. Identifying the risk factors associated with SOS/VOD can lead to more effective early treatment strategies of this potentially fatal HSCT complication in childhood.
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Usefulness of liver stiffness measurement in predicting hepatic veno-occlusive disease development in patients who undergo HSCT
Colecchia, A., Marasco, G., Ravaioli, F., Kleinschmidt, K., Masetti, R., Prete, A., Pession, A., Festi, D.
Bone Marrow Transplantation. 2017;52(3):494-497