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.

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