Hepatic sinusoidal obstruction syndrome/veno-occlusive disease after hematopoietic cell transplantation: historical and current considerations in Korea

Abstract

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare but severe complication of hematopoietic cell transplantation (HCT) showing high mortality. Multiple risk factors for SOS/VOD were identified, but it is often confused with other hepatic complications due to nonspecific clinical features. Therefore, diagnostic and severity criteria have been re vised several times. The European Society of Blood and Marrow Transplantation suggested a new guideline that excludes the standard duration of devel opment within 21 days, emphasizes late-onset SOS/VOD, and suggests the im portance of Doppler ultrasonography. The severity criteria were further subdivided for guidance to begin active treatment using defibrotide which was approved in Korea since 2016. In a phase 3 trial, defibrotide had superior 100-day survival, compared to best available treatments (38.2% vs. 25.0%). Although several studies of SOS/VOD in Korean patients have been performed after the implementation of HCT, most involved small number of pediatric patients. Recently, the Korean Society of Blood and Marrow Transplantation investigated the incidence of SOS/VOD in the Kore an population, and several influential studies of adult patients were published. Here, we summarize recent issues regarding the mechanism, diagnosis, severity criteria, prevention, and treatments of SOS/VOD in Korean patients, as well as recent analyses of nationwide incidence.

Veno-Occlusive Disease: A Life-Saving Novel Approach With Plasma Exchange, IVIG, and Steroid, Without Defibrotide

“…4,8 It is more commonly seen in hematopoietic stem cell transplantation (HSCT), but has also been reported in leukemia and solid tumors. 1,[9][10][11][12] Clinical manifestations include hepatomegaly, upper right abdominal tenderness, ascites, rapid weight gain, thrombocytopenia, and jaundice. 1,2,4,9 Diagnosis relies on established criteria such as the Baltimore, Modified Seattle, and EBMT Pediatric Criteria.…”

“…The condition typically arises due to exposure to high-dose chemotherapy, radiation therapy, or monoclonal antibodies 4,8 . It is more commonly seen in hematopoietic stem cell transplantation (HSCT), but has also been reported in leukemia and solid tumors 1,9-12 . Clinical manifestations include hepatomegaly, upper right abdominal tenderness, ascites, rapid weight gain, thrombocytopenia, and jaundice 1,2,4,9 .…”

Challenges to be addressed in management of patients with sinusoidal obstruction syndrome after hematopoietic cell transplantation

“…It is predicted that the diagnostic criteria will also affect the overall incidence evaluation of SOS. According to the data published by Yoon et al [ 7 ], the overall incidence of SOS ranged from 7.8% to 8.9% of all transplants. This incidence was lower than that reported in other large-scale studies (14% to 15%).…”

“…As about 200 cases of SOS occur after hematopoietic stem cell transplantation in Korea each year [ 7 ], only a limited number of subjects were analyzed over a long period of more than 18 years in this study. As a small-scale study, the analytical power was limited.…”

“…In Korea, defibrotide can be reimbursed by the national insurance system only when used in severe or very severe SOS, corresponding to the same conditions under which the drug’s effectiveness has been demonstrated in the literature. However, the disease course of SOS is dynamic and progresses rapidly to multiorgan failure within a few days [ 7 , 13 ]. Therefore, additional clinical studies are needed to confirm the advantages of early treatment so that active treatment can be applied before progression to severe or very severe disease where the use of defibrotide is currently approved.…”