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TRANSPLANTATION

Anti-Thrombin III in the Management of Hematopoietic Stem-Cell Transplantation–Associated Toxicity

Clinical Pharmacy Specialist (Hematology/Oncology), Karmanos Cancer Institute, Harper University Hospital, The Detroit Medical Center, Detroit, MI; Adjunct-Assistant Professor, Pharmacy Practice, Eugene Applebaum College of Pharmacy and Allied Health Professions, Wayne State University, Detroit

Edward Peres, MD

Pediatric Hematology/Oncology Fellow, Karmanos Cancer Institute, Children Hospital of Michigan, Wayne State University

Roger Dansey, MD

Bone Marrow Transplantation Service, Karmanos Cancer Institute; Associate Professor of Medicine, School of Medicine, Wayne State University

Muneer H Abidi, MD

Bone Marrow Transplantation Service, Karmanos Cancer Institute; Associate Professor of Medicine, School of Medicine, Wayne State University

Esteban M Abella, MD

Bone Marrow Transplantation Service, Karmanos Cancer Institute; Associate Professor of Medicine and Pediatrics, School of Medicine, Wayne State University

Jared Klein, MD

Bone Marrow Transplantation Service, Karmanos Cancer Institute; Associate Professor of Medicine, School of Medicine, Wayne State University

Reprints: Rami B Ibrahim MSc PharmD BCPS BCOP, Department of Pharmacy, Harper University Hospital, The Detroit Medical Center, 3990 John R, Detroit, MI 48201-2020, fax 313/745-1628, ribrahim{at}dmc.org

OBJECTIVE: To describe the evidence assessing the use of anti-thrombin III (AT-III) in the management of toxicity associated with hematopoietic stem-cell transplantation (HSCT)–conditioning regimens.

DATA SOURCES: Clinical literature was accessed through conference proceedings, EMBASE, the Cochrane database, and MEDLINE (1966–December 2003).

STUDY SELECTION AND DATA EXTRACTION: Case reports, small case series, case–control and cohort studies, and randomized controlled trials of AT-III in HSCT were evaluated. Publications examining AT-III use in the non-HSCT setting were also explored. Key search terms included AT-III, transplantation, and veno-occlusive disease (VOD).

DATA SYNTHESIS: Severe VOD and ensuing multiple organ dysfunction is associated with high mortality in HSCT. A low AT-III level has been shown to correlate with the development of organ dysfunction. Phase II trials, case series, and one small, randomized, placebo-controlled study suggest a benefit when AT-III therapy is instituted early in the course of VOD/multiple organ dysfunction syndrome. In all of these reports, AT-III use was devoid of adverse events.

CONCLUSIONS: Although further studies are needed to ascertain the optimal target level, method, and duration of administration, AT-III is still a viable alternative for the treatment of severe VOD and ensuing multiple organ dysfunction.

Key Words: anti-thrombin III, multiple organ dysfunction syndrome, stem-cell transplantation, veno-occlusive disease

Published Online, April 27, 2004. www.theannals.com, DOI 10.1345/aph.1D235

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