Comparison of valproate and levetiracetam for the prevention of busulfan-induced seizures in hematopoietic stem cell transplantation
- 172 Downloads
Anticonvulsant administration is the standard of care for prevention of busulfan-induced seizures (BIS) in hematopoietic stem cell transplantation (HSCT). While valproate interacts with other drugs, including carbapenem antibiotics, levetiracetam has no known clinically significant interactions. Only a few reports have discussed the use of levetiracetam for the prevention of BIS in HSCT recipients. This retrospective study aimed to evaluate the efficacy and safety of valproate and levetiracetam for BIS prophylaxis in adult HSCT recipients. We identified patients who received valproate or levetiracetam to prevent BIS at the National Cancer Center Hospital from December 2015 to November 2017. Ninety-one patients were analyzed (valproate group 45; levetiracetam group 46). No BIS occurred in either group. The pattern of anticonvulsant-related adverse events was similar in both groups, except for a higher incidence of rash in the valproate group. Carbapenem antibiotics were more frequently used in the levetiracetam group than in the valproate group. In conclusion, valproate and levetiracetam are effective and safe for the prophylaxis of BIS. Levetiracetam may be more useful in patients colonized with extended-spectrum beta-lactamase-producing bacteria due to its lack of any clinically significant drug–drug interactions.
KeywordsBusulfan Valproate Levetiracetam Hematopoietic stem cell transplantation Extended-spectrum beta-lactamase
TN, TT, TF, and HT designed the study. TN and TT performed the statistical analysis. KK, YN, HH, AI, YI, SK, and SWK reviewed the results. All authors wrote and critically revised the manuscript for important intellectual content, and approved the manuscript for publication.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
- 1.Vassal G, Deroussent A, Hartmann O, Challine D, Benhamou E, Valteau-Couanet D, et al. Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study. Cancer Res. 1990;50:6203–7.Google Scholar
- 6.Santos GW. Busulfan (Bu) and cyclophosphamide (Cy) for marrow transplantation. Bone Marrow Transpl. 1989;4(Suppl 1):236–9.Google Scholar
- 8.De La Camara R, Tomas JF, Figuera A, Berberana M, Fernandez-Ranada JM. High dose busulfan and seizures. Bone Marrow Transpl. 1991;7:363–4.Google Scholar
- 10.Saito AM, Kami M, Mori S, Kanda Y, Suzuki R, Mineishi S, et al. Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan. Am J Hematol. 2007;82:873–80.CrossRefGoogle Scholar
- 24.Beelen DW, Quabeck K, Graeven U, Sayer HG, Mahmoud HK, Schaefer UW. Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia. Blood. 1989;74:1507–16.Google Scholar
- 26.Sheridan WP, Boyd AW, Green MD, Russell DM, Thomas RJ, McGrath KM, et al. High-dose chemotherapy with busulphan and cyclophosphamide and bone-marrow transplantation for drug-sensitive malignancies in adults: a preliminary report. Med J Aust. 1989;151:379–86.Google Scholar
- 29.Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transpl. 2002;8:468–76.CrossRefGoogle Scholar
- 33.Shaw PJ, Scharping CE, Brian RJ, Earl JW. Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia. Blood. 1994;84:2357–62.Google Scholar
- 35.Meloni G, Nasta L, Pinto RM, Spalice A, Raucci U, Iannetti P. Clonazepam prophylaxis and busulfan-related myoclonic epilepsy in autografted acute leukemia patients. Haematologica. 1995;80:532–4.Google Scholar
- 43.Ren S, Yang JS, Kalhorn TF, Slattery JT. Oxidation of cyclophosphamide to 4-hydroxycyclophosphamide and deschloroethylcyclophosphamide in human liver microsomes. Cancer Res. 1997;57:4229–35.Google Scholar
- 47.Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, et al. Antiepileptic drugs–best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49:1239–76.CrossRefGoogle Scholar