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Volume 16, Issue 7 , Pages 1005-1017 , July 2010

Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease and Multiorgan Failure after Stem Cell Transplantation: A Multicenter, Randomized, Dose-Finding Trial

Paul G. Richardson
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
- Correspondence and reprint requests: Paul G. Richardson, MD, Dana-Farber Cancer Institute, 44 Binney Street, Dana 1B02, Boston, MA 02115.
Robert J. Soiffer
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Joseph H. Antin
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Hajime Uno
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts
Zhezhen Jin
- Department of Biostatistics, Columbia University, New York, New York
Joanne Kurtzberg
- Duke University Medical Center, Durham, North Carolina
Paul L. Martin
- Duke University Medical Center, Durham, North Carolina
Gideon Steinbach
- Fred Hutchinson Cancer Research Center, Seattle, Washington
Karen F. Murray
- Seattle Children's Hospital, Seattle, Washington
Georgia B. Vogelsang
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
Allen R. Chen
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
Amrita Krishnan
- City of Hope Cancer Center, Duarte, California
Nancy A. Kernan
- Memorial Sloan-Kettering Cancer Center, New York, New York
David E. Avigan
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Thomas R. Spitzer
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Howard M. Shulman
- Fred Hutchinson Cancer Research Center, Seattle, Washington
Donald N. Di Salvo
- Department of Radiology, Harvard Medical School, Dana-Farber Cancer Institute, and Brigham and Women's Hospital, Boston, Massachusetts
Carolyn Revta
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Diane Warren
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Parisa Momtaz
- Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital; Children's Hospital, and Harvard Medical School, Boston, Massachusetts
Gary Bradwin
- Department of Laboratory Medicine, Children's Hospital, Boston, Massachusetts
L.J. Wei
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
Massimo Iacobelli
- Gentium SpA, Villa Guardia, Como, Italy
George B. McDonald
- Fred Hutchinson Cancer Research Center, Seattle, Washington
Eva C. Guinan
- Department of Pediatrics, Dana-Farber Cancer Institute and Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts

Received 28 October 2009 ,Accepted 9 February 2010.

Disposition of patients. Flowchart illustrating the progression of patients with severe hepatic VOD after HSCT by treatment group (arm A, 25 mg/kg/day i.v. defibrotide; arm B, 40 mg/kg/day i.v. defibr

Disposition of patients. Flowchart illustrating the progression of patients with severe hepatic VOD after HSCT by treatment group (arm A, 25 mg/kg/day i.v. defibrotide; arm B, 40 mg/kg/day i.v. defibrotide).
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Survival of patients with severe hepatic VOD by treatment arm post-HSCT (A) and after randomization (B) (treated population). Kaplan-Meier curves show survival distributions for patients in treatment

Survival of patients with severe hepatic VOD by treatment arm post-HSCT (A) and after randomization (B) (treated population). Kaplan-Meier curves show survival distributions for patients in treatment arms A and B.
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Survival of patients with severe hepatic VOD by treatment arm for adult patients post-HSCT (A) and after randomization (B) and for pediatric patients post-HSCT (C) and after randomization (D) (treated

Survival of patients with severe hepatic VOD by treatment arm for adult patients post-HSCT (A) and after randomization (B) and for pediatric patients post-HSCT (C) and after randomization (D) (treated population). Kaplan-Meier curves show survival distributions for patients aged ≥18 years and aged <18 years.
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Mean (standard deviation) PAI-1 (A) and total bilirubin (B) by treatment arm and outcome in patients with severe hepatic VOD treated with i.v. defibrotide. Bar charts illustrate PAI-1 levels (A) and t

Mean (standard deviation) PAI-1 (A) and total bilirubin (B) by treatment arm and outcome in patients with severe hepatic VOD treated with i.v. defibrotide. Bar charts illustrate PAI-1 levels (A) and total bilirubin levels (B) by CR/nonresponse, day +100 post-HSCT survival/nonsurvival, and treatment arm. D, day; NR, nonresponder.
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