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Veno-occlusive Disease of the Liver and Multiorgan Failure after Bone Marrow Transplantation: A Cohort Study of 355 Patients

George B. McDonald, MD; Mary S. Hinds, RN; Lloyd D. Fisher, PhD; Howard G. Schoch, BS; John L. Wolford, MD; Meera Banaji, MD; Barbara J. Hardin, RRA; Howard M. Shulman, MD; and Reginald A. Clift, FIMLS
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From the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, Seattle, Washington. Acknowledgments: The authors thank Bruce Ballard, Fred Drennan, Finn Peterson, and Scott Bearman for their assistance; and to Michelle Tesler, Jami Martin, Lok Lee, and Doris Martin for their help with data entry. Grant Support: In part by grants CA18029 and CA15704 from the National Institutes of Health Public Health Service and by grants from the Bristol-Myers Company and the Carl Inserra Leukemia Fund.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1993;118(4):255-267. doi:10.7326/0003-4819-118-4-199302150-00003
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Objective: To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD.

Design: Cohort study of 355 consecutive patients.

Setting: A bone marrow transplantation center.

Measurements: Each patient was prospectively evaluated for VOD, and many risk factors for severe VOD were analyzed using logistic regression models. The relation of VOD to renal and cardiopulmonary failure was analyzed using time-dependent proportional hazards models.

Results: Veno-occlusive disease developed in 190 of 355 patients (54%; 95% CI, 48% to 59%): Fifty-four patients had severe VOD and 136 had mild or moderate VOD. Independent variables derived from a multivariate model for predicting severe VOD included elevated transaminase values before transplantation (relative risk, 4.6; P < 0.0001); vancomycin therapy during cytoreductive therapy (relative risk, 2.9; P = 0.003); cytoreductive therapy with a high-dose regimen (relative risk, 2.8; P = 0.01); acyclovir therapy before transplantation (relative risk, 4.8; P = 0.02); mismatched or unrelated donor marrow (relative risk, 2.4; P = 0.02); and previous radiation therapy to the abdomen (relative risk, 2.2; P = 0.04). Vancomycin therapy was a marker for persistent fever. Multiorgan failure was more frequent among patients with VOD and usually followed the onset of liver disease.

Conclusions: Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure. Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD.





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