title: Intravenous busulfan-based conditioning prior to allogeneic hematopoietic stem cell transplantation: myeloablation with reduced toxicity.
abstract: OBJECTIVE
  Allogeneic transplantation is a potentially curative treatment for hematologic malignancies but is associated with a high rate of complications. Busulfan is a common component of pretransplant conditioning but has an erratic and unpredictable bioavailability when administered orally. Intravenous (IV) busulfan was recently introduced into clinical practice. Prior studies showed consistent and predictable drug delivery with tight control of busulfan plasma levels, avoiding over- and under-dosing. This study was designed to define the role of IV busulfan in different transplant and disease settings.
  
  
  METHODS
  The study included 43 patients with various hematologic malignancies conditioned with high-dose IV busulfan-containing regimens prior to allogeneic transplantation. The donors were HLA-matched siblings (n=24), matched unrelated (n=14), or 1-antigen mismatched related donors (n=5). Outcome parameters were recorded.
  
  
  RESULTS
  Forty-two patients had initial engraftment. The toxicity profile was favorable. No patient developed veno-occlusive disease of the liver. Acute graft-vs-host disease (GVHD) grades II-IV occurred in 18 patients (42%). Six patients died of treatment-related causes, five of complications related to acute GVHD, and only one died of organ toxicity. Actuarial non-relapse-related mortality risk was 10% at day 100 and 18% at 2 years posttransplant. The actuarial 2-year overall survival and disease-free survival (DFS) rates were 63% and 44%, respectively. Disease status other than refractory relapse, myeloid disease, and no severe GVHD posttransplant predicted for longer DFS in a multivariant model.
  
  
  CONCLUSIONS
  IV busulfan-containing regimens allow consistent engraftment of allografts from related and unrelated donors such that myeloablation is administered with a toxicity profile typical of non-myeloablative conditioning. Favorable outcome was seen in patients with myeloid leukemias and in early or intermediately advanced disease; however, this regimen may not be sufficiently cytoreductive in patients with very advanced or active leukemia and in acute lymphoblastic leukemia. IV busulfan merits further study to better define its role as a preferred substitute for oral busulfan in pretransplant conditioning.
authors.affiliation: Department of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel. ashimoni@sheba.health.gov.il
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Bella
authors.initials: B
authors.lastname: Bielorai
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
authors.forename: Izhar
authors.initials: I
authors.lastname: Hardan
authors.forename: Abraham
authors.initials: A
authors.lastname: Avigdor
authors.forename: Moshe
authors.initials: M
authors.lastname: Yeshurun
authors.forename: Isaac
authors.initials: I
authors.lastname: Ben-Bassat
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan