Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation

Cheuk, Dkl; Wang, P; Lee, T L; Chiang, Alan Kwok Shing; Ha, Sy; Lau, Yu Lung; Chan, Godfrey Chi‐Fung

doi:10.1038/sj.bmt.1705835

Cited by 94 publications

(90 citation statements)

References 23 publications

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“…[21][22][23]35,39,40,42 Age and/or weight have been found to be risk factors of VOD. 21,44,45 PK and pharmacodynamics of drugs in infants can differ widely between children and adults, owing to developmental changes in physiological and metabolic processes, which may alter drug disposition. 46,47 In the study of Nguyen et al, 18 only four patients weighed o 9 kg (16.7%) and none weighed o7.1 kg.…”

Section: Discussionmentioning

confidence: 99%

Should busulfan therapeutic range be narrowed in pediatrics? Experience from a large cohort of hematopoietic stem cell transplant children

Philippe

Goutelle

Guitton

et al. 2015

Bone Marrow Transplant

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Busulfan, the corner stone of hematopoietic stem cell transplantation regimens, has a narrow therapeutic window. Therapeutic drug monitoring (TDM)-guided dosing to reach the conventional area under the concentration-time curve (AUC) target range of 900-1500 μmol min/L is associated with better outcomes. We report our experience with busulfan TDM in a large cohort of children. The aims were to investigate the relevance of using a more restricted therapeutic range and investigate the association between busulfan therapeutic range and clinical outcome. This study includes 138 children receiving 16 doses of intravenous busulfan, with the first dose assigned based on weight and doses adjusted to a local AUC target range of 980-1250 μmol min/L. Busulfan TDM combined with model-based dose adjustment was associated with an increased probability of AUC target attainment, for both target range: 90.8% versus 74.8% for the conventional target range and 66.2% versus 43.9% for the local target range (P o 0.001). The median follow-up was 56.2 months. Event-free survival was 88.5%, overall survival was 91.5% and venoocclusive disease occurred in 18.3% of patients. No difference was observed for clinical outcomes depending on the selected target range. Pharmacokinetic monitoring and individualization of busulfan dosage regimen are useful in improving target attainment, but using a restricted target range has no impact on clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Should busulfan therapeutic range be narrowed in pediatrics? Experience from a large cohort of hematopoietic stem cell transplant children

Philippe

Goutelle

Guitton

et al. 2015

Bone Marrow Transplant

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“…In previous studies, the incidence of hepatic VOD showed a range between 5% and 39%. 1,2,4 In our cohort, VOD developed in 22 of 204 patients who received a HSCT, with a rate of 10.8%. The relatively low incidence of VOD in the present study is attributed to the use of HLA fully-matched donors in 91% of transplants and improvements in supportive therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Owing to narrow sinusoid lumens leading to easy occlusion, it was defined as a risk factor for VOD in previous studies but not in our cohort. 2 Meanwhile, several diseases-such as thalassemia major, osteopetrosis, and hemophagocytic lymphohistiocytosis-especially during childhood, have been proposed to increase risk of VOD. 2,5 In our study, the patients were divided in 9 disease groups.…”

Section: Discussionmentioning

confidence: 99%

“…In pediatric population, its incidence shows a wide range between 5% to 39% because of differences in the underlying risk factors. 1,2 Pre-existing liver disease, younger age, gemtuzumab-ozogamicin, myeloablative conditioning regimens with busulphan (BU), total parenteral nutrition (TPN), previous abdominal radiotherapy and pediatric diseases such as hemophagocytic lymphohistiocytosis and osteopetrosis are wellestablished risk factors for VOD. [2][3][4][5] Several agents, such as classic heparin, lowmolecular-weight heparin, prostaglandin E1, have been tried to prevent of VOD but unfortunately, the results of these studies are inconclusive .…”

Section: Introductionmentioning

confidence: 99%

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Coexisting or Underlying Risk Factors of Hepatic Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients Receiving Prophylaxis

Gökçe

Kuşkonmaz²,

Çetin³

et al. 2013

Exp Clin Transplant

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Objectives: To evaluate the characteristics of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients, and their effect as a prophylactic regimen on severity and outcome. Materials and Methods: This study included 204 allogeneic hematopoietic stem cell transplants performed on 187 children whose data retrospectively described the risk factors, prophylaxis, and treatment modalities of veno-occlusive disease. A prophylactic regimen composed of enoxaparin versus ursodeoxycholic acid and vitamin E was given to 167 of 204 patients. Results: Veno-occlusive disease developed in 22 patients (10.8%). Nineteen patients experienced veno-occlusive disease despite this prophylactic regimen. The prophylaxis seemed ineffective in preventing veno-occlusive disease (P = .657). Regarding risk factors, oral busulphan use, liposomal amphotericin B vancomycin treatment, and total parenteral nutrition were associated with an increased risk of veno-occlusive disease. Conversely, renal impairment also was associated with increased mortality in patients with veno-occlusive disease. The mortality rate in the first 100 days after a hematopoietic stem cell transplant was higher in the patients with veno-occlusive disease than it was in those without the disease. Conclusions: Our prophylactic regimen may have played a role in the fairly low incidence of venoocclusive disease in a pediatric population with highrisk features.

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“…[8][9][10][11] The recipients of stem cells from MR donors have lower risk of infections, 8,9 of cytomegalovirus (CMV) reactivation 10 and of mortality 11 than the latter group (for statistical significance and details of different HLA disparities, see Table 3). The T-cell immunity reconstitution is delayed in the mismatchedsibling donors and UD group.…”

Section: Effect Of Hla Disparity On Hsctmentioning

confidence: 99%

Role of HLA in hematopoietic SCT

Nowak

2008

Bone Marrow Transplant

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HLA disparity between hematopoietic stem cell (HSC) donor and recipient triggers T-cell and NK-cell allorecognition, and induces the GVHD, GVL effect and/or may cause an engraftment failure. This review will cover the scope of human genomic variation, the methods of HLA typing and interpretation of high-resolution HLA results. We describe the main subsets of related and unrelated HSC donors and outline the main aspects of HLA disparity and their effect on the outcome of the patients after allogeneic HSC transplantation (HSCT). The HLA match between HSCT donor and recipient is crucial, but for many patients a perfectly matched donor is not available. The HSCT from the alternative mismatched donor with one allele/antigen mismatch (9/10) can be as beneficial as a HSCT from a fully matched donor, especially in younger patients. For the remaining patients, the donors with permissive mismatches may be the option. The permissiveness depends not only on the potential adverse effect of the HLA mismatches, but also on the urgency of the transplantation, the desirable GVL effect and the potential efficacy of the alternative therapy available for the patient.

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Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation

Cited by 94 publications

References 23 publications

Should busulfan therapeutic range be narrowed in pediatrics? Experience from a large cohort of hematopoietic stem cell transplant children

Should busulfan therapeutic range be narrowed in pediatrics? Experience from a large cohort of hematopoietic stem cell transplant children

Coexisting or Underlying Risk Factors of Hepatic Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients Receiving Prophylaxis

Role of HLA in hematopoietic SCT

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