title: Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre- and post-transplantation cyclophosphamide.
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 μmol*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 μmol*min/L, irrespective of Bu administration route.
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Lindsey R
authors: LR
authors: Lombardi
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Christopher G
authors: CG
authors: Kanakry
authors: b Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA.
authors: Marianna
authors: M
authors: Zahurak
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Nadira
authors: N
authors: Durakovic
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Javier
authors: J
authors: Bolaños-Meade
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Yvette L
authors: YL
authors: Kasamon
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Douglas E
authors: DE
authors: Gladstone
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: William
authors: W
authors: Matsui
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Ivan
authors: I
authors: Borrello
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Carol Ann
authors: CA
authors: Huff
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Lode J
authors: LJ
authors: Swinnen
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Robert A
authors: RA
authors: Brodsky
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Richard F
authors: RF
authors: Ambinder
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Ephraim J
authors: EJ
authors: Fuchs
authors: b Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA.
authors: Gary L
authors: GL
authors: Rosner
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Richard J
authors: RJ
authors: Jones
authors: a Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University , Baltimore , MD , USA and.
authors: Leo
authors: L
authors: Luznik
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016903:Drug Monitoring; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan
keywords: Busulfan; post-transplantation cyclophosphamide; route; toxicity