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

被引:332
作者
de Lima, M
Couriel, D
Thall, PF
Wang, XM
Madden, T
Jones, R
Shpall, EJ
Shahjahan, M
Pierre, B
Giralt, S
Korbling, M
Russell, JA
Champlin, RE
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
关键词
D O I
10.1182/blood-2004-02-0414
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:857 / 864
页数:8
相关论文
共 53 条
  • [1] Acute safety and pharmacokinetics of intravenous busulfan when used with oval busulfan and cyclophosphamide as pretransplantation conditioning therapy: A phase I study
    Andersson, BS
    Madden, T
    Tran, HT
    Hu, WW
    Blume, KG
    Chow, DSL
    Champlin, RE
    Vaughan, WP
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2000, 6 (5A) : 548 - 554
  • [2] Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: Defining a therapeutic window for IV BuCy2 in chronic myelogenous leukemia
    Andersson, BS
    Thall, PF
    Madden, T
    Couriel, D
    Wang, XM
    Tran, HT
    Anderlini, P
    de Lima, M
    Gajewski, J
    Champlin, RE
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2002, 8 (09) : 477 - 485
  • [3] Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: A phase II study
    Andersson, BS
    Kashyap, A
    Gian, V
    Wingard, JR
    Fernandez, H
    Cagnoni, PJ
    Jones, RB
    Tarantolo, S
    Hu, WW
    Blume, KG
    Forman, SJ
    Champlin, RE
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2002, 8 (03) : 145 - 154
  • [4] Benet L.Z., 1985, GOODMAN GILMANS PHAR, P8
  • [5] Formulation and stability of busulfan for intravenous administration in high-dose chemotherapy
    Bhagwatwar, HP
    Phadungpojna, S
    Chow, DSL
    Andersson, BS
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1996, 37 (05) : 401 - 408
  • [6] BLUME KG, 1993, BLOOD, V81, P2187
  • [7] Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells
    Bornhäuser, M
    Storer, B
    Slattery, JT
    Appelbaum, FR
    Deeg, HJ
    Hansen, J
    Martin, PJ
    McDonald, GB
    Nichols, WG
    Radich, J
    Woolfrey, A
    Jenke, A
    Schleyer, E
    Thiede, C
    Ehninger, G
    Anasetti, C
    [J]. BLOOD, 2003, 102 (03) : 820 - 826
  • [8] ROBUST LOCALLY WEIGHTED REGRESSION AND SMOOTHING SCATTERPLOTS
    CLEVELAND, WS
    [J]. JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1979, 74 (368) : 829 - 836
  • [9] Congdon P., 2001, BAYESIAN STAT MODELI, DOI DOI 10.1002/9780470035948
  • [10] COX DR, 1972, J R STAT SOC B, V34, P187