ORIGINAL ARTICLE Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation DKL Cheuk, P Wang, TL Lee, AKS Chiang, SY Ha, YL Lau and GCF Chan Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), Hong Kong, China A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997–2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1–21 days after HSCT (median 13 days). Age p2 years at transplant (odds ratio (OR) ¼ 5.25, P ¼ 0.011), BU–CY conditioning (OR ¼ 5.16, P ¼ 0.001), thalassemia major (OR ¼ 3.97, P ¼ 0.015), platelet en- graftment beyond day þ 21 (OR ¼ 8.67, P ¼ 0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30–421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5–9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P ¼ 0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR) ¼ 23.6, P ¼ 0.006), hepatic and cutaneous GVHD (HR ¼ 8.15, P ¼ 0.038), maximal weight gain 49% (HR ¼ 6.81, P ¼ 0.023), pleural effusion, intensive care unit admission, peak bilirubin 4300 lmoll 1 (HR ¼ 13.6, P ¼ 0.016), day þ 21 bilirubin 4200 lmoll 1 (HR ¼ 33.9, P ¼ 0.001), and rise of bilirubin 415 lmoll 1 per day within the first week (HR ¼ 19.8, P ¼ 0.006). Mortality was substantially higher if 43 predictors were present (HR ¼ 33.9, P ¼ 0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage. Bone Marrow Transplantation (2007) 40, 935–944; doi:10.1038/sj.bmt.1705835; published online 3 September 2007 Keywords: children; hematopoietic stem cell transplanta- tion; veno-occlusive disease; risk factor; prognosis; mortality Introduction Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is one of the important complications of hematopoietic stem cell transplant (HSCT). Its incidence ranges from 5 to 39% in pediatric patients. 1,2 The cause of hepatic VOD is not entirely clear but a number of risk factors have been reported. 3–6 While many cases of mild VOD resolve spontaneously without complications, moderate-to-severe VOD may result in significant morbidity or even mortality. The management of VOD is mainly supportive, including fluid restriction and diuretics to ameliorate fluid retention and cardio-respira- tory support if necessary. Anticoagulants and thrombolytic therapies were tried with only limited success. A newer agent, defibrotide, is increasingly used and has been reported to be useful in several studies. 7,8 Since only a limited number of studies on hepatic VOD after pediatric HSCT are currently available, we would like to evaluate the incidence, management and outcomes of hepatic VOD in children after HSCT in our center, with particular focus on risk factors and mortality predictors of hepatic VOD. Materials and methods Study design and participants This was a retrospective review of all pediatric HSCT performed in Queen Mary Hospital, a University-affiliated quaternary referral center in Hong Kong, over the past 10 years (January 1997 – December 2006). Most of the patients are Chinese, and a few patients are of Southeast Asian ethnicities. The patients’ data on demographic and clinical characteristics, progress in the post transplant period including occurrence and treatment of hepatic VOD, and final outcomes were extracted. Apart from centrally stored hospital records, patients’ information was retrieved and verified from our Hematology–Oncology– Immunology database through our Departmental Compu- ter Server. Additional relevant clinical information includ- ing laboratory results was also retrieved by the Clinical Management System (CMS) of the Hospital Authority Server. All patients were nursed in air-filtered rooms with laminar airflow from the start of conditioning until neutrophil engraftment. Standard protocols were adopted Received 22 May 2007; revised 23 July 2007; accepted 24 July 2007; published online 3 September 2007 Correspondence: Dr DKL Cheuk, Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, 121 Pokfulam Road, Hong Kong Special Administrative Region (SAR), Hong Kong, China. E-mail: cheukkld@hkucc.hku.hk Bone Marrow Transplantation (2007) 40, 935–944 & 2007 Nature Publishing Group All rights reserved 0268-3369/07 $30.00 www.nature.com/bmt