Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning |
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| Affiliation: | 1. Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, WA, USA;2. Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA;3. CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;4. Adult HSCT Program, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;5. Department of Medicine, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL, USA;6. Department of Medicine, Oregon Health and Science University Hospital, Portland, OR, USA;7. Department of Medicine, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France;8. Department of Medicine, University of Massachusetts Memorial Medical Center, Worcester, MA, USA;9. Department of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI;10. Division of Oncology, West Virginia University Hospitals, Morgantown, WV, USA;11. The Hospital for Sick Children and Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada;12. Department of Medicine, Case Western Reserve University, Cleveland, OH, USA;13. Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK;14. Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA;15. Blood and Cancer Centre, Starship Child Health, Central Auckland, New Zealand;16. Department of Medicine, Penn State Hershey Medical Center, Hershey, PA, USA;17. Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA;18. Department of Population Sciences, City of Hope, Duarte, CA, USA |
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| Abstract: | High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative antiepileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Lower exposure to active CY metabolites with the use of alternative AEMs could decrease the risk of toxicity but might increase the risk of recurrent malignancy after HCT. Previous studies have not determined whether outcomes with alternative AEMs differ from those with phenytoin in patients treated with BU/CY before allogeneic HCT. We studied a cohort of 2155 patients, including 1460 treated with phenytoin and 695 treated with alternative AEMs, who received BU/CY before allogeneic HCT between 2004 and 2014. We found no differences suggesting decreased overall survival or relapse-free survival or increased risks of relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or regimen-related toxicity associated with the use of alternative AEMs compared with phenytoin. The risk of dialysis was lower in the alternative AEM group than in the phenytoin group. Alternative AEMs are safe for prevention of seizures after BU administration and can avoid the undesirable toxicities and drug interactions caused by phenytoin. |
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