Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS
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de Lima, M
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
de Lima, M
Couriel, D
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Couriel, D
Thall, PF
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Thall, PF
Wang, XM
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Wang, XM
Madden, T
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Madden, T
Jones, R
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Jones, R
Shpall, EJ
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Shpall, EJ
Shahjahan, M
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Shahjahan, M
Pierre, B
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Pierre, B
Giralt, S
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Giralt, S
Korbling, M
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Korbling, M
Russell, JA
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Russell, JA
Champlin, RE
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Champlin, RE
Andersson, BS
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机构:Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
Andersson, BS
机构:
[1] Univ Texas, MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplant, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Pharmaceut Dev Ctr, Houston, TX 77030 USA
[3] Alberta Bone Marrow Transplant Program, Calgary, AB, Canada
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/m(2) and intravenous busul-fan 130 mg/m(2) 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 mumol-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.