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

Abstract

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 ¼ 0.002), VOD prophylaxis without lipo-prostaglandin E1 (PGE1) (P ¼ 0.012), number of previous HSCT (P ¼ 0.014), and pretransplant serum ferritin (P ¼ 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) (Po0.001). 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.

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation

“…Elevated serum ferritin has also been associated with increased risk of bacterial infection, 7,8 mucositis, 9 acute GvHD, 10 chronic liver disease, 11 and SOS. 12,24 However, because serum ferritin is an imperfect measure of total body iron, the exact prognostic role of iron overload in allo-HSCT remains to be determined. Several prospective studies and a multi-center meta-analysis examining the impact of elevated LIC on HSCT outcomes came to different conclusions regarding the prognostic relevance of LIC in HSCT, mainly due to the use of different LIC thresholds.…”

Consolidation Therapy for Newly Diagnosed Pediatric Patients with High-Risk Neuroblastoma Using Busulfan/Melphalan, Autologous Hematopoietic Cell Transplantation, Anti-GD2 Antibody, Granulocyte-Macrophage Colony–Stimulating Factor, Interleukin-2, and Haploidentical Natural Killer Cells

“…The risk of VOD is influenced by the agents used during conditioning chemotherapy, with busulfan being of particular concern 36–38 . It is important to interpret VOD in the context of the criteria, prophylactic regimen and grading systems used, as these factors are not uniform across institutions.…”

Emergent Complications in the Pediatric Hematopoietic Stem Cell Transplant Patient

“…Risk factors for the development of VOD are the use of busulfan, cyclophosphamide, melphalan, or total body radiation in the conditioning regimen; prior abdominal radiation; elevated ferritin prior to transplant; recent exposure to gemtuzumab ozogamicin (anti-CD33 antibody used, particularly in patients with acute myeloid leukemia); and history of previous HCT. 44-48 Treatment of mild and moderate VOD is supportive with fluid and sodium restriction, as well as minimization of hepatotoxic medications. There is increasing evidence that defibrotide is an efficacious treatment even in cases of severe VOD involving multiorgan failure.…”