title: High-dose methylprednisolone for veno-occlusive disease of the liver in pediatric hematopoietic stem cell transplantation recipients.
abstract: Veno-occlusive disease (VOD) of the liver is a well-recognized serious complication of hematopoietic stem cell transplantation (HSCT), with few successful treatment modalities available for severe disease. Some reports have demonstrated success in adults with the use of high-dose steroid therapy, but experience in the pediatric population is lacking. We retrospectively reviewed HSCT patients treated at our institution since 2003 and identified 15 (2.4%) who developed VOD. Of these, nine (60%) were treated with intravenous high-dose methylprednisolone (500 mg/m(2) per dose every 12 hours for six doses). Steroid therapy was initiated at or before first ultrasound evidence of reversal of portal venous flow and before meeting criteria for initiation of defibrotide therapy. Four patients were also treated with defibrotide starting 2 to 5 days after initiation of steroids. Eight of nine patients (88%) with VOD were diagnosed with multiorgan failure. Response to high-dose steroid therapy as defined by decrease in bilirubin by 50% in 10 days from therapy initiation was noted in six of nine patients (67%), occurring within 3 to 6 days of steroid therapy. Two patients died from multiorgan failure due to VOD. Seven survivors of VOD recovered at the median 6 days (range, 5 to 38) from VOD diagnosis. Overall, VOD survival as a group was 78%; however, survival among responders was 100%. No serious toxicities related to high-dose steroid therapy were observed. We conclude that high-dose steroid therapy if initiated early may reverse VOD of the liver in pediatric HSCT patients, abrogating the need for defibrotide therapy with its associated toxicities and regulatory difficulties.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati, OH 45229, USA. kasiani.myers@cchmc.org
authors.forename: Kasiani C
authors.initials: KC
authors.lastname: Myers
authors.forename: Julia
authors.initials: J
authors.lastname: Lawrence
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000517:prevention & control; D006402:Hematologic Diseases / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D005343:Fibrinolytic Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D008775:Methylprednisolone