Veno-occlusive Disease In Children Research Articles

Point shear-wave elastography for the diagnosis of veno-occlusive disease in children and young adults.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome is a potentially life-threatening complication of hematopoietic stem cell transplantation. To assessthe usefulness of point shear-wave elastography (pSWE) for theearly diagnosis of sinusoidal obstruction syndrome (SOS) in children. A retrospective study was carried out in 43 patients with suspected SOS assessed between March 2018 and November 2021. Diagnosis of SOS was confirmed in 28 patients based on the European Society for Blood and Marrow Transplantation diagnostic criteria. Abdominal ultrasound and pSWE of the liver were performed before and afterhematopoietic stem cell transplantation on first suspicion of SOS. Liver stiffness on initial suspicion was higher in patients diagnosed with SOS and these values increased compared to the pre-transplantation values. A cutoff value of 1.37m/s was found for the diagnosis of SOS, with an area under the curve of 0.779 (95% CI 0.61-0.93). Point shear wave elastography of the liver is a promising technique for theearly diagnosis of pediatric SOS.

The changes in the diagnostics and treatment of hepatic veno-occlusive disease in children

The changes in the diagnostics and treatment of hepatic veno-occlusive disease in children

Association Between the Magnitude of Intravenous Busulfan Exposure and Development of Hepatic Veno-Occlusive Disease in Children and Young Adults Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation

Intravenous busulfan is widely used as part of myeloablative conditioning regimens in children and young adults undergoing allogeneic hematopoietic cell transplantation (HCT). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious clinical problem observed with busulfan-based conditioning HCT. The development of VOD/SOS may be associated with busulfan exposure. Getting more insight into the association between busulfan exposure and the development of VOD/SOS enables further optimization of dosing and treatment strategies. The objective of this study was to assess the association between the magnitude of busulfan exposure and the occurrence of VOD/SOS in children and young adults undergoing myeloablative conditioning with a busulfan-containing regimen before allogeneic HCT. In this observational study we included all patients who underwent allogeneic HCT with intravenous busulfan as part of the conditioning regimen at 15 pediatric transplantation centers between 2000 and 2015. The endpoint was the development of VOD/SOS. The magnitude of busulfan exposure was estimated using nonlinear mixed effect modeling and expressed as the maximal concentration (Cmax; day 1 and day 1 to 4 Cmax), cumulative area under the curve (AUC; day 1, highest 1-day AUC in 4 days, and 4-day cumulative AUC), cumulative time above a concentration of 300 µg/L, and clearance on day 1. A total of 88 out of 697 patients (12.6%) developed VOD/SOS. The number of alkylators in the conditioning regimen was a strong effect modifier; therefore we stratified the regression analysis for the number of alkylators. For patients receiving only busulfan as one alkylator (36.3%, n = 253), cumulative busulfan exposure (>78 mg × h/L) was associated with increased VOD/SOS risk (12.6% versus 4.7%; odds ratio [OR] = 2.95, 95% confidence interval [CI] 1.13 to 7.66). For individuals receiving busulfan with one or two additional alkylators (63.7%, n = 444), cumulative busulfan exposure (≤78 and >78 mg × h/L) did not further increase the risk of VOD/SOS (15.4% versus 15.2%; OR = 1.03, 95% CI 0.61 to 1.75). The effect of the magnitude of busulfan exposure on VOD/SOS risk in children and young adults undergoing HCT is dependent on the number of alkylators. In patients receiving busulfan as the only alkylator, higher cumulative busulfan exposure increased the risk of VOD/SOS, whereas in those receiving multiple alkylators, the magnitude of busulfan exposure did not further increase this risk.

Imaging features of hepatic sinusoidal obstruction syndrome or veno-occlusive disease in children

Hepatic sinusoidal obstruction syndrome, also known as veno-occlusive disease, can occur as a complication of myeloablative chemotherapy, as a result of low-intensity chemotherapy-related liver toxicity or radiotherapy of the liver. Symptoms of sinusoidal obstruction syndrome can range from asymptomatic to liver dysfunction or severe disease with life-threatening acute multi-organ failure. Imaging features can suggest or support this clinical diagnosis. Familiarity with the imaging spectrum of sinusoidal obstruction syndrome is therefore important for both radiologists and clinical oncologists. Here, multi-modality radiologic appearances of sinusoidal obstruction syndrome in pediatric patients are illustrated, including outcome after follow-up.

Veno-occlusive disease in children and adolescents after hematopoietic stem cell transplantation: Did the Modified Seattle Criteria fit the characteristics of pediatric population?

Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT) and associated with a high mortality rate. Therefore, accurate and immediate diagnosis is crucial for implementing appropriate treatment. In our single-center retrospective study, we assessed the accuracy of the Modified Seattle Criteria in children and adolescents undergoing HSCT, and compared them to the diagnostic criteria recently established by the European Society for Blood and Marrow Transplantation (EBMT). Retrospective analysis of medical records of 951 HSCT procedures performed in 850 children and young adults in the years 2001-2015 in the Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation of Wroclaw Medical University Supraregional Center of Pediatric Oncology "Cape of Hope" in Wrocław, Poland. Among the 850 children, 48 were diagnosed with VOD according to the Modified Seattle Criteria (5.05%). Thirteen patients (27%) developed VOD later than within 20 days after transplantation, as required in the diagnostic criteria. Five of the 6 patients who died from VOD were diagnosed with late-onset VOD. Using the categories of symptoms described in the Modified Seattle Criteria, hepatomegaly and weight gain were the most common symptoms in the analyzed cohort (81.25% and 68.75%). Fourteen patients (29%) never demonstrated elevated plasma bilirubin level (>2 mg/dL), as suggested in the Modified Seattle Criteria. Twenty-nine patients (64%) had increased platelet consumption requiring daily transfusions. Only 5 patients with decreased plasma antithrombin III (ATIII) activity level (<80%) on the day of HSCT developed VOD despite supplementation of ATIII. The Modified Seattle Criteria seemed to not meet the special needs of the pediatric population. The new diagnostic criteria proposed by the EBMT appear to be more adequately tailored to the pediatric population and may significantly change the conception of VOD in the future. The surprisingly low incidence of VOD in our cohort may suggest a beneficial role of monitoring and early supplementation of ATIII.

The Role of Interventional Radiology in the Treatment of Acute Thrombosis and Chronic Veno-Occlusive Disease in Children and Adolescents

Abstract Pediatric venous thromboembolic disease is increasing in incidence in both inpatient and outpatient populations. A collaborative, multidisciplinary approach between interventional radiology (IR), hematology, anesthesiology, and critical care medicine provides the highest level of care for such patients. This review focuses on the clinical management of venous thromboembolic disease and the potential role of pediatric IR in treating these conditions.

Treatment of hepatic veno-occlusive disease in children with N-acetylcysteine.

In our institution, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) has been treated with N-acetylcysteine (NAC) since 2008-a loading dose of 150mg/kg, followed by 12 doses of 70mg/kg 6 hourly. Nine children were diagnosed with hepatic VOD/SOS. Hepatic VOD/SOS occurred in seven children after stem cell transplantation and two were receiving chemotherapy for Wilms tumor. Their clinical severity was classified as moderate in two and severe in seven by the European Society for Blood and Marrow Transplantation criteria. All children recovered and were discharged from 4 to 16days after diagnosis. No side effects were observed. Intravenous NAC is an effective treatment for hepatic VOD/SOS.

Maximal concentration of intravenous busulfan as a determinant of veno-occlusive disease: a pharmacokinetic-pharmacodynamic analysis in 293 hematopoietic stem cell transplanted children.

Veno-occlusive disease (VOD) is a severe adverse reaction to busulfan-containing regimens used in the preparation of children for hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis of data to examine determinants of VOD in children who received IV busulfan for HSCT conditioning. Busulfan PK parameters as well as various indices (maximal concentration-Cmax, area under the concentration-time curve-AUC) were estimated using a validated Bayesian approach. The influence of available PK, demographic, and clinical variables on the incidence of VOD was evaluated by using logistic regression and classification and regression tree (CART) analyses. Among the 293 patients included, the mean age was 6.5 years and the mean actual body weight was 26.3 kg. The incidence of VOD was 25.6%. Busulfan Cmax as well as weight <9 kg or age <3 years were identified as independent predictors of VOD in logistic regression analysis. CART analysis identified busulfan Cmax over the entire regimen as the strongest predictor of VOD. This study suggests that busulfan-associated VOD is in part a concentration-dependent reaction. In addition, the youngest children showed the highest risk of VOD. These findings may have important implications for busulfan dosing and therapeutic drug monitoring practice in HSCT children.

610 - Frequency of Veno-Occlusive Disease in Children with B-Thalassemia Major Who Underwent Hematopoietic Stem Cell Transplantation

610 - Frequency of Veno-Occlusive Disease in Children with B-Thalassemia Major Who Underwent Hematopoietic Stem Cell Transplantation

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 3: Focus on Cardiorespiratory Dysfunction, Infections, Liver Dysfunction, and Delirium

Some patients with veno-occlusive disease (VOD) have multiorgan dysfunction, and multiple teams are involved in their daily care in the pediatric intensive care unit. Cardiorespiratory dysfunction is critical in these patients, requiring immediate action. The decision of whether to use a noninvasive or an invasive ventilation strategy may be difficult in the setting of mucositis or other comorbidities in patients with VOD. Similarly, monitoring of organ functions may be very challenging in these patients, who may have fulminant hepatic failure with or without hepatic encephalopathy complicated by delirium and/or infections. In this final guideline of our series on supportive care in patients with VOD, we address some of these questions and provide evidence-based recommendations on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2—Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues

Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provide standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. We consider the available evidence using the GRADE criteria.

High Variability in the Reported Management of Hepatic Veno-Occlusive Disease in Children after Hematopoietic Stem Cell Transplantation

Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Patients with VOD are often critically ill and require close collaboration between transplant physicians and intensivists. We surveyed members of a consortium of pediatric intensive care unit (PICU) and transplant physicians to assess variability in the self-reported approach to the diagnosis and management of VOD. An internet-based self-administered survey was sent to pediatric HSCT and PICU providers from September 2014 to February 2015. The survey contained questions relating to the diagnosis and treatment of VOD. The response rate was 41% of 382 providers surveyed. We found significant variability in the diagnostic and management approaches to VOD in children. Even though ultrasound is not part of the diagnostic criteria, providers reported using reversal of portal venous flow seen on abdominal ultrasound in addition to Seattle criteria (70%) or Baltimore criteria to make the diagnosis of VOD. Almost 40% of respondents did not diagnose VOD in anicteric patients (bilirubin < 2 mg/dL). Most providers (75%) initiated treatment with defibrotide at the time of diagnosis, but 14%, 7%, and 6% of the providers waited for reversal of portal venous flow, renal dysfunction, or pulmonary dysfunction, respectively, to develop before initiating therapy. Only 50% of the providers restricted fluids to 75% of the daily maintenance, whereas 21% did not restrict fluids at all. Albumin with diuretics was used by 95% of respondents. Platelets counts were maintained at 20,000 to 50,000/mm3 and 10,000 to 20,000/mm3 by 64% and 20% of the respondents, respectively. Paracentesis was generally initiated in the setting of oliguria or hypoxia, and nearly 50% of the providers used continuous drainage to gravity, whereas the remainder used an intermittent drainage approach. Nearly 73% of the transplant providers used VOD prophylaxis, whereas the remainder did not use any medications for VOD prophylaxis. There was also considerable variation in the management strategies among the transplant and critical care providers. We conclude that there is considerable self-reported variability in the diagnosis and management of VOD in children. The practice variations reported in this study should encourage the development of standard practice guidelines, which will be helpful in improving the outcome of this potentially fatal complication.

Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is a potentially fatal complication, which occurs in 7-27% of children undergoing hematopoietic stem cell transplantation. In this article, we review commonly accepted diagnostic criteria, atypical diagnostic features as well as preventative and treatment measures associated with VOD. Reversal of portal venous flow by Doppler ultrasound is often a late finding; many patients with anicteric VOD may never develop hyperbilirubinemia, and yet perish from severe VOD. Transjugular liver biopsy is usually not available and/or is often avoided. Prophylactic therapies with ursodeoxycholic acid, heparin and defibrotide are discussed. Supportive care with fluid restriction and diuretic therapy, analgesia, blood and platelet transfusions, paracentesis as well as other pulmonary and renal therapies remain imperative to superior outcomes. Specific therapy with thrombolytics such as defibrotide and recombinant tissue plasminogen activator is discussed and a classification of severity of VOD is proposed.

Experience from a single paediatric transplant centre with identification of some protective and risk factors concerning the development of hepatic veno-occlusive disease in children after allogeneic hematopoietic stem cell transplant

Hepatic veno-occlusive disease (VOD) is a frequent and severe complication of hematopoietic stem cell transplantation (HSCT) affecting 9.6-17.3 % of cases. 200 HSCT, performed between January 1995 and March 2013 in our Paediatric HSCT Centre in Trieste, were retrospectively analysed to evaluate the frequency of VOD and to identify the associated risk factors. The frequency of VOD according to the Seattle criteria was 17 %, within the range reported in literature. The mortality rate was 37.5 % (75 out of 200 transplantations) in the general population and 73.5 % (25 out of 34) in VOD patients (p < 0.05). Veno-occlusive disease significantly decreased from 38 % (1995-2000) to 8 % (2007-2013) p < 0.05. Univariate and multivariate analyses identified sepsis and pre-transplant ferritin levels above 1000 ng/ml as two significant risk factors for VOD, while the use of tacrolimus appeared to be associated with a lower VOD risk. Veno-occlusive disease still remains an important cause of transplant-related mortality even if it appears to have decreased over the last few years.

Association of Cth Genetic Variant with Veno-Occlusive Disease in Children Receiving Intravenous Busulfan Before Hematopoietic Stem Cell Transplantation.

AbstractAbstract 3025 Background:Busulfan (Bu) is a key compound given prior to hematopoietic stem cell transplantation (HSCT), in children. Bu has a narrow therapeutic index, where high Bu exposure often leads to increased risk of veno-occlusive disease (VOD), whereas low Bu exposure has been associated with a higher risk of disease recurrence and graft failure. Interindividual differences in drug response are an important cause of resistance to treatment and toxicity. Identifying pharmacogenetic determinants of a given drug may allow for prospective identification of patients with suboptimal drug responses allowing for complementation of traditional treatment protocols by genotype-based drug dose adjustment.Bu is primarily eliminated via the GSH conjugation in the liver, catalyzed by glutathione s-transferases (GSTs). The Bu glutathione conjugate is then converted to tetrahydrothiophene by cystathionine gamma lyase (CTH). CTH is mainly expressed in the liver and is also essential for glutathione synthesis. Any defective function with CTH could reduce Bu's elimination by preventing its metabolite formation or by decreasing the amount of glutathione needed for conjugation. Thus we investigated the relationship between genetic variants of CTH and HSCT-related toxicity. Hypothesis:A defective function (caused by genetic variants) of CTH will reduce Bu's metabolism resulting in increased toxicity. Sample and Methods:The study was performed on sixty six pediatric patients (50% males, mean age 7.8yrs) who underwent allogeneic HSCT with intravenous BU as part of a myeloablative conditioning regimen. Bu dose was adjusted to target Css of 600–900 ng/ml and ursodeoxycholic acid was provided as a prophylaxis for VOD. Genomic DNA collected prior to myeloablation was used for genotyping rs1021737, using a Taqman SNP genotyping Assay. Rs1021737 is a common non-synonymous SNP, with a 1364G>T transition, resulting in a Ser403Ile (S403I) mutation. In Caucasians this SNP has the following frequencies: GG (54%), GT (38%) and TT (7%). We used PANTHER, a computational method designed to predict the biological impact of SNPs and rs1021737 was predicted to be deleterious. Results:Patients were followed for up to 5yrs. Neutrophil, platelet recoveries, grade 1–4 acute versus host disease, treatment related mortality incidences were 87.9, 84.9, 19.7 and 10.6%, respectively. Overall survival rate was 77%, Events free Survival resulted in 60.6%, while 21.2% of patients relapsed and 10.6% had primary or secondary graft failure. Incidence of VOD (Seattle criteria), hemorrhagic cystitis and lung toxicity were 12.1, 25.8 and 9.1% respectively. Genotype frequencies for rs1021737 within our sample were GG (54.5%), GT (40.9%) and TT (4.5%), similar to the general population. No association was found with clinical outcomes except with VOD. A Chi-Square test demonstrated that the homozygous TT genotype correlated with VOD (p=0.031), with an odds ratio of 19 (95% Confidence Interval; 1.5–241.7). We extended this analysis by performing a multidimensional reduction analysis which included: rs1021737 and GSTA1*B haplotype (a functional variant which has previously been associated with VOD in our sample). The analysis demonstrated that these two variants provided good predictability of VOD risk (accuracy =86%, specificity = 91%, sensitivity = 50%) with a Chi-square p=0.001 and odds ratio of 12.4 (2.36 – 65.13). Discussion and Conclusion:Our results suggest an association between CTH 1364G>T variant and VOD in children receiving IV Bu before HSCT. Loss of function of CTH may result in the accumulation of Bu and depletion of glutathione, which is involved in the removal of Bu, and thus homozygous TT individuals are at risk of VOD compared to GG or GT individuals. CTH is also vital in the production of Hydrogen Sulfide which is a protective factor in kidney and liver function. Diminished function of CTH results in cellular damage and inflammation and thus the pathogenesis of VOD may also be related to this biological mechanism. Furthermore, by including the CTH 1364G>T in a polygenic analysis, with the previously associated GSTA1*B, the predictability of VOD improved. This study suggests that genes involved in the metabolism of Bu may help in identifying patients at risk of developing VOD and who will therefore need a better VOD prophylaxis, maybe by administering defibrotide. A prospective multicentre study is ongoing to confirm these results. Disclosures:No relevant conflicts of interest to declare.

Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation

Hepatic veno-occlusive disease (VOD) is a serious complication of stem cell transplantation in children. VOD is characterized by rapid weight gain, hepatomegaly, hyperbilirubinemia and ascites. The pathogenesis of VOD is thought to involve chemotherapy and radiation-induced damage to the sinusoidal endothelium, resulting in endothelial injury, microthrombosis, subendothelial damage and cytokine activation. These processes lead to concomitant progressive hepatocellular dysfunction and subsequent fluid retention and renal impairment. Severe VOD is typically associated with multiorgan failure and high mortality. A number of possible strategies for the prevention and/or treatment of VOD in children have been investigated. The most promising agent to date is defibrotide, a novel polydeoxyribonucleotide with fibrinolytic properties but no major bleeding risk. Numerous studies, including Phase II/III trials, have shown clinical benefit in pediatric patients with the use of defibrotide treatment and prophylaxis. This review discusses VOD in children and focuses on therapeutic options, including defibrotide, in this patient population.

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial

AbstractThe Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (± 1.8%) and to MP was 79.0% (± 2.1%; P = .004 log rank), although overall survival was 91.9% (± 1.4%) and 91.2% (± 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m2 per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m2 (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.

Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation: incidence, risk factors, and outcome

Four hundred and sixty-seven hematopoietic stem cell transplantations (HSCTs) (217 autologous and 250 allogeneic HSCT) were performed in 374 children at four pediatric HSCT centers in Korea from January 2005 to December 2007. Among 467 transplants, veno-occlusive disease (VOD) developed in 72 transplants (15.4%) at a median of 10 days after HSCT. Multivariate analysis showed that BU or TBI-containing regimen (P=0.002), VOD prophylaxis without lipo-prostaglandin E1 (PGE1) (P=0.012), number of previous HSCT (P=0.014), and pretransplant serum ferritin (P=0.018) were independent risk factors for developing VOD. Mean serum ferritin levels were significantly higher in HSCT with VOD (2109.6+/-2842.5 ng/ml) than in HSCT without VOD (1315.9+/-1094.4 ng/ml) (P<0.001). The relative risk of death within 100 days of HSCT in transplants with VOD compared with transplants without VOD was 3.39 (confidence interval: 1.78-6.45). Our results suggest that lipo-PGE1 might have a protective effect against the development of VOD, and pretransplant serum ferritin could act as a risk factor for VOD. A larger prospective study is needed to confirm a possible role of lipo-PGE1 and iron chelation therapy in reducing the incidence of VOD.

Hepatic veno-occlusive disease in children with acute lymphoma leukemia after CAT chemotherapy: report of 2 cases

目的 探讨儿童急性淋巴细胞白血病CAT方案(环磷酰胺、阿糖胞苷、6-硫代鸟嘌呤)治疗后发生肝静脉闭塞病(HVOD)的病因、临床表现、影像学特征及治疗方案.方法 分析CAT治疗后发生HVOD患儿的临床资料并复习文献.结果 2例患儿治疗后血常规、肝功能、出凝血项、彩色多普勒检查中肝静脉显影及腹水、胸水均较治疗前明显改善.结论 CAT治疗儿童急性淋巴细胞白血病发生HVOD可能与化疗药物联合作用有关,去纤苷是一种相对有效且安全的治疗HVOD药物。

Hepatic Veno-Occlusive Disease in Children after Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, and Outcome

Veno-occlusive disease (VOD) is one of the most frequent complications after hematopoietic stem cell transplantation (HSCT). We conducted this study to describe recent characteristics of incidence, risk factors, treatment and outcome of VOD in children undergoing autologous or allogeneic HSCT. Patients who underwent HSCT with hematological malignancies, solid tumors, or nonmalignant diseases at Asan Medical Center, National Cancer Center, Samsung Medical Center, and Seoul National University Children's Hospital in Korea, from January 2005 to December 2007, were assessed with chart review. VOD was defined according to McDonald criteria and classified as severe on the basis of persistent symptoms after day 100 or death before day 100 with ongoing VOD. All other patients were considered to have mild or moderate VOD. Descriptive statistics and univariate and multivariate analyses of risk factors are presented. Four hundred sixty-seven HSCTs (217 autologous and 250 allogeneic HSCTs) were performed in 374 patients for the treatment of leukemia (n=177, 37.9%), neuroblastoma (n=103, 22.1%), brain tumors (n=69, 14.8%), nonmalignant diseases (n=62, 13.3%), and other solid tumors (n=56, 12.0%). For VOD prophylaxis, heparin was used in 116 transplants, heparin + prostaglandin E1 (PGE1) in 230 transplants, PGE1 ± ursodeoxycholic acid in 86 transplants, and defibrotide + heparin in 35 transplants. Among 467 transplant procedures, VOD developed in 72 transplants (15.4%) at median 10 days (range, 1–64) after HSCT. Five patients had recurrent VOD in their tandem transplantation. VOD was mild or moderate in 62 transplants and severe in 10 transplants. For treatment of VOD, PGE1, tissue-plasminogen activator, defibrotide, or antithrombin III were given alone or in combination of each other in 42 transplants. In remaining 30 VOD-positive transplants, patients were treated with supportive care only, such as restriction of sodium and fluid intake, diuretics and hematologic support. The median duration of VOD was 12 days (range, 3–80). Hepatomegaly was the most common sign of VOD (n=63). Ascites and inversion of portal flow were found in 17 (23.6%) and 8 (11.1%) of 72 VOD-positive transplants, respectively. VOD-related respiratory dysfunction and renal dysfunction were more frequent in transplants with severe VOD (7/10 and 7/10) compared to transplants with mild or moderate VOD (9/62 and 8/62) (P=0.001 and P<0.0005). Multivariate analysis showed that total body irradiation (TBI) or busulfan containing regimen (P=0.003), VOD prophylaxis without PGE1 (P=0.005), pre-transplant serum ferritin (P=0.005), and number of previous HSCT (P=0.038) were independent risk factors for developing VOD. Underlying disease, stem cell source, donor type, age at transplantation, pre-transplant serum aspartate aminotransferase, and alanine aminotransferase did not influence the development of VOD. In addition, ascites (P=0.017) and number of previous HSCT (P=0.037) were significant risk factors for severe VOD by multivariate analysis. Deaths within 100 days after transplantation occurred in 13 of 72 VOD-positive transplants, the cause of death being VOD-related multi-organ failure in 5 cases. The risk of death within 100 days after HSCT was 2.8 times higher (95% CI: 1.718, 4.563) for VOD-positive transplants (P<0.0005). TBI or busulfan-based conditioning regimen, VOD prophylaxis without PGE1, pre-transplant ferritin level, and repeated HSCT increased significantly the incidence of VOD in children after HSCT. The results can be used to identify high risk patients who are to undergo an HSCT. The encouraging result of our study is to justify the role of PGE1 in the prophylaxis of VOD, however prospective randomized trials are needed to confirm the superior efficacy of PGE1 in preventing VOD. Despite the combination of supportive cares and VOD therapy, significant numbers of patients are still suffering from VOD. Continued research for prevention and effective treatment of VOD will be necessary to improve the outcome of HSCT.