TY - JOUR
T1 - Once-daily intravenous busulfan and fludarabine
T2 - Clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS
AU - De Lima, Marcos
AU - Couriel, Daniel
AU - Thall, Peter F.
AU - Wang, Xuemei
AU - Madden, Timothy
AU - Jones, Roy
AU - Shpall, Elizabeth J.
AU - Shahjahan, Munir
AU - Pierre, Betty
AU - Giralt, Sergio
AU - Korbling, Martin
AU - Russell, James A.
AU - Champlin, Richard E.
AU - Andersson, Borje S
PY - 2004/8/1
Y1 - 2004/8/1
N2 - Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m2 and intravenous busulfan 130 mg/m2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years). Only 20% of the patients were in first complete remission (CR) at transplantation. Donors were HLA-compatible related (n = 60) or matched unrelated (n = 36). The CR rate for 54 patients with active disease was 85%. At a median follow-up of 12 months, 1-year regimen-related and treatment-related mortalities were 1% and 3%, respectively. Two patients had reversible hepatic veno-occlusive disease. Actuarial 1-year overall survival (OS) and event-free survival (EFS) were 65% and 52% for all patients, and 81% and 75% for patients receiving transplants in CR. Recipient age and donor type did not influence OS or EFS. Median busulfan clearance was 109 mL/min/m 2 and median daily area-under-the-plasma-concentration-versus-time- curve was 4871 μmol-min, with negligible interdose variability in pharmacokinetic parameters. The results suggest that intravenous busulfan-fludarabine is an efficacious, reduced-toxicity, myeloablative- conditioning regimen for patients with AML or MDS undergoing HSCT.
AB - Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m2 and intravenous busulfan 130 mg/m2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years). Only 20% of the patients were in first complete remission (CR) at transplantation. Donors were HLA-compatible related (n = 60) or matched unrelated (n = 36). The CR rate for 54 patients with active disease was 85%. At a median follow-up of 12 months, 1-year regimen-related and treatment-related mortalities were 1% and 3%, respectively. Two patients had reversible hepatic veno-occlusive disease. Actuarial 1-year overall survival (OS) and event-free survival (EFS) were 65% and 52% for all patients, and 81% and 75% for patients receiving transplants in CR. Recipient age and donor type did not influence OS or EFS. Median busulfan clearance was 109 mL/min/m 2 and median daily area-under-the-plasma-concentration-versus-time- curve was 4871 μmol-min, with negligible interdose variability in pharmacokinetic parameters. The results suggest that intravenous busulfan-fludarabine is an efficacious, reduced-toxicity, myeloablative- conditioning regimen for patients with AML or MDS undergoing HSCT.
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U2 - 10.1182/blood-2004-02-0414
DO - 10.1182/blood-2004-02-0414
M3 - Article
C2 - 15073038
AN - SCOPUS:3242810563
SN - 0006-4971
VL - 104
SP - 857
EP - 864
JO - Blood
JF - Blood
IS - 3
ER -