Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation

Abstract

The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome with Multiorgan Failure

“…Children differ substantially from adults, with an incidence of VOD/ SOS approximately two-to three-fold higher overall [4,[7][8][9], and rates as high as 30-60% in highrisk subpopulations like infants and those with inherited diseases like familial hemophagocytic lymphohistiocytosis, thalassemia [10] and osteopetrosis [7,11,12]. Clinical presentation also differs in children, who often lack hyperbilirubinemia [4,7,13,14], the hallmark of VOD/SOS. Development of VOD/SOS after HSCT involves a complex pathophysiologic cascade initiated by the toxic injury from the conditioning regimen, with subsequent endothelial-cell damage and activation, and a prothrombotichypofibrinolytic state leading to central venous occlusion and/or sinusoidal obstruction [1,15,16].…”

“…Although regimen-related risk factors are similar in adults and children, the impact of patientrelated risk factors is greater in children than in adults [4]. Both varying presence of risk factors in study populations and use of the Baltimore or modified Seattle criteria for identification and diagnosis of VOD/SOS across studies have contributed to the wide range in VOD/SOS prevalence rates reported in post-HSCT patients [5].…”

“…VOD/SOS with multiorgan failure (MOF; also sometimes referred to as multiorgan dysfunction) occurs in an estimated 30-40% of patients with VOD/SOS after HSCT [6], and carries a mortality rate that exceeds 80% [5]. Children differ substantially from adults, with an incidence of VOD/ SOS approximately two-to three-fold higher overall [4,[7][8][9], and rates as high as 30-60% in highrisk subpopulations like infants and those with inherited diseases like familial hemophagocytic lymphohistiocytosis, thalassemia [10] and osteopetrosis [7,11,12]. Clinical presentation also differs in children, who often lack hyperbilirubinemia [4,7,13,14], the hallmark of VOD/SOS.…”

“…Although less common, VOD/SOS also may develop as a result of primary chemotherapy, immunotoxin conjugated therapies or radiation, particularly in children [1][2][3][4]. Mean prevalence of VOD/SOS among post-HSCT patients was estimated to be 13.7% (95% confidence interval [CI] = 13.3-14.1%), based on a review of 135 studies, each conducted in more than 50 patients between 1979 and 2007 [5].…”

“…Consequently, the EBMT has proposed new diagnostic criteria for adults that distinguish 'classical' VOD/SOS occurring within 21 days after HSCT, using the Baltimore criteria for these patients, and 'late-onset' VOD/ SOS, occurring >21 days after HSCT [22]. New EBMT diagnostic criteria for VOD/SOS that are specifically for pediatric patients were recently published; these pediatric criteria differ in some aspects from those for adults [4]. For example, there is no limitation for time of onset for pediatric patients.…”