@article{a28ac6d276be43899aa7166605d0db79,
title = "Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning",
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.",
keywords = "Antiepileptic medication, Busulfan, Cyclophosphamide, Drug interactions, Hematopoietic cell transplantation, Phenytoin, Seizure prophylaxis",
author = "McCune, {Jeannine S.} and Tao Wang and Khalid Bo-Subait and Mahmoud Aljurf and Amer Beitinjaneh and Joseph Bubalo and Cahn, {Jean Yves} and Jan Cerny and Saurabh Chhabra and A. Cumpston and Dupuis, {L. Lee} and Lazarus, {Hillard M.} and Marks, {David I.} and Maziarz, {Richard T.} and M. Norkin and Tim Prestidge and Shin Mineishi and Krem, {Maxwell M.} and Marcelo Pasquini and Martin, {Paul J.}",
note = "Funding Information: The authors thank the HCT centers that provided data; the physicians, nurses, physician assistants, nurse practitioners, pharmacists, and support staff caring for the patients; and the staff who maintain the CIBMTR repository. Members of the Regimen-Related Toxicity Working Committee who reviewed this project include Hisham Abdel-Azim, Muneer Abidi, Allistair Abrahim, Kehinde Adekola, Vaibhav Agrawal, Ibrahim Ahmed, Gorgun Akpek, A Samer Al-Homsi, Arnon Nagler, Jeffery Auletta, Pere Barba, Asad Bashey, Nelli Bejanyan, Christopher Bredeson, Stefan Ciurea, Edward Copelan, Marcos De Lima, Miguel Angel Diaz Perez, Anita D'Souza, John Edwards, Nosha Farhadfar, Shatha Farhan, Haydar Frangoul, Cesar Freytes, Sidhartha Ganguly, Usama Gergis, Eva Guinan, Gregory Hale, Shahrukh Hashmi, Peiman Heimatti, Gerhard Hildebrandt, Leona Holmberg, Sanghee Hong, Ann Jakubowski, Amy Keating, Oscar Lahoud, Jane Liesveld, Mark Litzow, Navneet Majhail, Parinda Mehta, Herman Murthy, Taiga Nishihori, Roomi Nusrat, Richard Olsson, Attaphol Pawarode, Miguel-Angel Perales, Robert Peter Gale, Mohamed Radhi, Voravit Ratanatharathorn, Andrew Rezvani, Dadiv Rizzieri, Seth Rotz, Jacob Rowe, Ayman Saad, Bipin Savani, Harry Schouten, Mathew Seftel, Sachiko Seo, Niketa Shah, Amir Steinberg, Nathan Sunita, Matthew Ulrickson, Celalettin Ustun, John Wagner, Edmund Waller, Kirsten Williams, Mona B. Wirk, and Jean Yared. Financial disclosure: This work was supported by the National Institutes of Health, National Cancer Institute (NCI) Grant CA182963. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the NCI, the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 4U10HL069294 from the NHLBI and NCI; Contract HHSH250201200016C from the Health Resources and Services Administration; Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, *Amgen, *Amneal Biosciences; *Angiocrine Bioscience, anonymous donation to the Medical College of Wisconsin, Astellas Pharma US, Atara Biotherapeutics, Be The Match Foundation, *bluebird bio, *Bristol Myers Squibb Oncology, *Celgene, Cerus, *Chimerix, Fred Hutchinson Cancer Research Center, Gamida Cell, Gilead Sciences, HistoGenetics, Immucor; *Incyte, Janssen Scientific Affairs, *Jazz Pharmaceuticals, Juno Therapeutics, Karyopharm Therapeutics, Kite Pharma, Medac, MedImmune, The Medical College of Wisconsin, *Mediware, *Merck & Co, *Mesoblast, MesoScale Diagnostics, Millennium, the Takeda Oncology Co, *Miltenyi Biotec, National Marrow Donor Program, *Neovii Biotech NA, Novartis Pharmaceuticals, Otsuka Pharmaceutical, PCORI, *Pfizer, *Pharmacyclics, PIRCHE, *Sanofi Genzyme, *Seattle Genetics. Shire. Spectrum Pharmaceuticals, St Baldrick's Foundation, *Sunesis Pharmaceuticals, Swedish Orphan Biovitrum, Takeda Oncology, Telomere Diagnostics, and the University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, the Health Resources and Services Administration, or any other agency of the US Government. *Corporate member. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement; J.S.M. T.W. K.B-S, M.P. and P.J.M. analyzed the data and created the figures. J.S.M. T.W. M.P. and P.J.M. designed the research and wrote the manuscript. All other coauthors provided data and edited the manuscript for critical content, and all authors approved the manuscript for submission. Financial disclosure: See Acknowledgments on page 1430. Funding Information: Financial disclosure: This work was supported by the National Institutes of Health , National Cancer Institute (NCI) Grant CA182963. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the NCI, the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases ; Grant/Cooperative Agreement 4U10HL069294 from the NHLBI and NCI; Contract HHSH250201200016C from the Health Resources and Services Administration; Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research ; and grants from *Actinium Pharmaceuticals, *Amgen, *Amneal Biosciences; *Angiocrine Bioscience, anonymous donation to the Medical College of Wisconsin, Astellas Pharma US, Atara Biotherapeutics, Be The Match Foundation, *bluebird bio, *Bristol Myers Squibb Oncology, *Celgene, Cerus, *Chimerix, Fred Hutchinson Cancer Research Center, Gamida Cell, Gilead Sciences, HistoGenetics, Immucor; *Incyte, Janssen Scientific Affairs, *Jazz Pharmaceuticals, Juno Therapeutics, Karyopharm Therapeutics, Kite Pharma, Medac, MedImmune, The Medical College of Wisconsin, *Mediware, *Merck & Co, *Mesoblast, MesoScale Diagnostics, Millennium, the Takeda Oncology Co, *Miltenyi Biotec, National Marrow Donor Program, *Neovii Biotech NA, Novartis Pharmaceuticals, Otsuka Pharmaceutical, PCORI, *Pfizer, *Pharmacyclics, PIRCHE, *Sanofi Genzyme, *Seattle Genetics. Shire. Spectrum Pharmaceuticals, St Baldrick's Foundation, *Sunesis Pharmaceuticals, Swedish Orphan Biovitrum, Takeda Oncology, Telomere Diagnostics, and the University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, the Health Resources and Services Administration, or any other agency of the US Government. Publisher Copyright: {\textcopyright} 2019 American Society for Blood and Marrow Transplantation",
year = "2019",
month = jul,
doi = "10.1016/j.bbmt.2019.03.001",
language = "English (US)",
volume = "25",
pages = "1424--1431",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "7",
}