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

Ann Hematol. 2005 May;84(5):321-30. doi: 10.1007/s00277-004-0982-4. Epub 2004 Dec 4.

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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Proteins / analysis
  • Bone Marrow Transplantation*
  • Busulfan / administration & dosage*
  • Busulfan / adverse effects
  • Case-Control Studies
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Female
  • Hepatic Veno-Occlusive Disease* / blood
  • Hepatic Veno-Occlusive Disease* / chemically induced
  • Humans
  • Incidence
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Odds Ratio
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Blood Proteins
  • Cyclophosphamide
  • Busulfan