title: Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation.
abstract: We investigated the occurrence of hepatic veno-occlusive disease (VOD) after allogeneic bone marrow transplantation (BMT) in 241 adults conditioned with busulfan + cyclophosphamide at a single institute and retrospectively compared 186 patients who received oral busulfan (O-Bu group) with 55 patients who received intravenous busulfan (I-Bu group). Various hemostatic parameters were determined at baseline and on days 0, 7, 14, and 21. Hepatic VOD occurred in 41.7% of the O-Bu group and in 18.5% of the I-Bu group. Multivariate analysis revealed that the I-Bu group had significantly decreased risk of VOD compared to the O-Bu group [p=0.006, odds ratio: (OR) 0.345]. Eleven patients in the O-Bu group and none of the I-Bu group developed severe VOD. A repeated measures analysis of variance (ANOVA) with a between-subjects factor revealed significant differences in post-transplant levels of antithrombin III, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and D-dimer according to the occurrence of VOD. The level of antithrombin III was significantly lower, whereas the level of D-dimer was significantly higher, in the O-Bu group than in the I-Bu group. These findings show that, in adults conditioned with busulfan + cyclophosphamide, intravenous busulfan was associated with significantly decreased incidence of VOD and fewer hemostatic derangements after allogeneic BMT compared to oral busulfan.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, 388-1 Poongnap-2-dong, Songpa-gu, Seoul 138-736, South Korea. jhlee3@amc.seoul.kr
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Seong-Jun
authors.initials: SJ
authors.lastname: Choi
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: So-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Chi
authors.forename: Moo-Song
authors.initials: MS
authors.lastname: Lee
authors.forename: Jung-Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Woo-Kun
authors.initials: WK
authors.lastname: Kim
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001798:Blood Proteins / Q000032:analysis; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D001798:Blood Proteins; D003520:Cyclophosphamide; D002066:Busulfan