Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre- and post-transplantation cyclophosphamide. Issue 3 (3rd March 2016)

• Record Type: Journal Article
• Authors: Lombardi, Lindsey R.; Kanakry, Christopher G.; Zahurak, Marianna; Durakovic, Nadira; Bolaños-Meade, Javier; Kasamon, Yvette L.; Gladstone, Douglas E.; Matsui, William; Borrello, Ivan; Huff, Carol Ann; Swinnen, Lode J.; Brodsky, Robert A.; Ambinder, Richard F.; Fuchs, Ephraim J.; Rosner, Gary L.; Jones, Richard J.; Luznik, Leo
• Is Part Of: Leukemia & lymphoma. Volume 57:Issue 3(2016:Mar.)
• Page Start: 666
• Page End: 675
• Publication Date: 2016-03-03
• Subjects: Busulfan -- post-transplantation cyclophosphamide -- route -- toxicity; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2015.1071488
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), providing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally ( n = 72) or intravenously ( n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800–1400 μ mol*min/L per dose. BuCy/PTCy with pharmacokinetics is well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive disease incidence was 6% with two fatal events. Bu administration route in the context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse, disease-free survival, or overall survival. The BuCy/PTCy platform has a low incidence of treatment-related toxicity, including hepatotoxicity, in hematologic malignancies when using pharmacokinetics for a target AUC of 800–1400 μ mol*min/L, irrespective of Bu administration route.