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Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning. Biol Blood Marrow Transplant 2019 07;25(7):1424-1431

Date

03/16/2019

Pubmed ID

30871976

Pubmed Central ID

PMC6615968

DOI

10.1016/j.bbmt.2019.03.001

Scopus ID

2-s2.0-85064251855

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.

Author List

McCune JS, Wang T, Bo-Subait K, Aljurf M, Beitinjaneh A, Bubalo J, Cahn JY, Cerny J, Chhabra S, Cumpston A, Dupuis LL, Lazarus HM, Marks DI, Maziarz RT, Norkin M, Prestidge T, Mineishi S, Krem MM, Pasquini M, Martin PJ

Authors

Saurabh Chhabra MD Associate Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Allografts
Anticonvulsants
Busulfan
Child
Child, Preschool
Cyclophosphamide
Disease-Free Survival
Female
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Middle Aged
Phenytoin
Seizures
Survival Rate
Transplantation Conditioning
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a