Veno-occlusive disease after high-dose busulfan-melphalan in neuroblastoma.

TitleVeno-occlusive disease after high-dose busulfan-melphalan in neuroblastoma.
Publication TypeJournal Article
Year of Publication2020
AuthorsSchechter T, Perez-Albuerne E, Lin TF, Irwin MS, Essa M, Desai AV, Frangoul H, Yanik G, L Dupuis L, Jacobsohn D, Kletzel M, Ranalli M, Soni S, Seif AE, Grupp S, Dvorak CC
JournalBone Marrow Transplant
Volume55
Issue3
Pagination531-537
Date Published2020 03
ISSN1476-5365
KeywordsBusulfan, Child, Hematopoietic Stem Cell Transplantation, Hepatic Veno-Occlusive Disease, Humans, Melphalan, Neuroblastoma, Transplantation Conditioning
Abstract

Survival for high-risk neuroblastoma patients is still suboptimal. Although stem cell transplantation (SCT) is used, there is no consensus as to which conditioning regimen has the greatest efficacy and fewest toxicities. We assessed the incidence of and risk for hepatic veno-occlusive disease (VOD) for neuroblastoma patients who underwent autologous SCT with busulfan and melphalan (BuMel) at eight centers following Children's Oncology Group (COG)-based induction chemotherapy. Data regarding the patients, SCT characteristics, busulfan steady-state concentrations, incidence of VOD, and survival were evaluated. VOD was defined using the modified Seattle criteria. Possible factors associated with VOD (age, busulfan-pharmacokinetic parameters, history of hepatic dysfunction, and day of neutrophil engraftment) were evaluated. Seventy five patients were included and 23 children (31%) developed VOD at a median of 19 days after SCT (range 14-27 days). VOD was the cause of death in 4 patients (5%). In a multivariable analysis, young age (OR 1.7 (95% CI: 1.16-2.56; p = 0.012)) and early day of neutrophil engraftment (OR 1.4 (95% CI: 1.08-2.14; p = 0.041) were associated with the development of VOD. Initial or cumulative busulfan steady-state concentration were not associated with VOD. We found that despite the use of intravenous busulfan with adjusted serum levels, the incidence of VOD remains high in pediatric neuroblastoma patients.

DOI10.1038/s41409-018-0298-y
Alternate JournalBone Marrow Transplant
PubMed ID30181580