Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning

Jeannine S. McCune, Tao Wang, Khalid Bo-Subait, Mahmoud Aljurf, Amer Beitinjaneh, Joseph Bubalo, Jean Yves Cahn, Jan Cerny, Saurabh Chhabra, Aaron Cumpston, L. Lee Dupuis, Hillard M. Lazarus, David I. Marks, Richard Maziarz, Maxim Norkin, Tim Prestidge, Shin Mineishi, Maxwell M. Krem, Marcelo Pasquini, Paul J. Martin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StatePublished - Jan 1 2019

Fingerprint

Busulfan
Cell Transplantation
Phenytoin
Anticonvulsants
Cyclophosphamide
Hematologic Neoplasms
Seizures
Recurrence
Survival
Graft vs Host Disease
Drug Interactions
Dialysis
Mortality
Enzymes

Keywords

  • Antiepileptic medication
  • Busulfan
  • Cyclophosphamide
  • Drug interactions
  • Hematopoietic cell transplantation
  • Phenytoin
  • Seizure prophylaxis

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning. / McCune, Jeannine S.; Wang, Tao; Bo-Subait, Khalid; Aljurf, Mahmoud; Beitinjaneh, Amer; Bubalo, Joseph; Cahn, Jean Yves; Cerny, Jan; Chhabra, Saurabh; Cumpston, Aaron; Dupuis, L. Lee; Lazarus, Hillard M.; Marks, David I.; Maziarz, Richard; Norkin, Maxim; Prestidge, Tim; Mineishi, Shin; Krem, Maxwell M.; Pasquini, Marcelo; Martin, Paul J.

In: Biology of Blood and Marrow Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

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, R, Norkin, M, Prestidge, T, Mineishi, S, Krem, MM, Pasquini, M & Martin, PJ 2019, 'Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2019.03.001
McCune, Jeannine S. ; Wang, Tao ; Bo-Subait, Khalid ; Aljurf, Mahmoud ; Beitinjaneh, Amer ; Bubalo, Joseph ; Cahn, Jean Yves ; Cerny, Jan ; Chhabra, Saurabh ; Cumpston, Aaron ; Dupuis, L. Lee ; Lazarus, Hillard M. ; Marks, David I. ; Maziarz, Richard ; Norkin, Maxim ; Prestidge, Tim ; Mineishi, Shin ; Krem, Maxwell M. ; Pasquini, Marcelo ; Martin, Paul J. / Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning. In: Biology of Blood and Marrow Transplantation. 2019.
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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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AU - McCune, Jeannine S.

AU - Wang, Tao

AU - Bo-Subait, Khalid

AU - Aljurf, Mahmoud

AU - Beitinjaneh, Amer

AU - Bubalo, Joseph

AU - Cahn, Jean Yves

AU - Cerny, Jan

AU - Chhabra, Saurabh

AU - Cumpston, Aaron

AU - Dupuis, L. Lee

AU - Lazarus, Hillard M.

AU - Marks, David I.

AU - Maziarz, Richard

AU - Norkin, Maxim

AU - Prestidge, Tim

AU - Mineishi, Shin

AU - Krem, Maxwell M.

AU - Pasquini, Marcelo

AU - Martin, Paul J.

PY - 2019/1/1

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N2 - 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.

AB - 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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