Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jan 2002
Clinical TrialOnce-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes.
The availability of an i.v. form of busulfan (Bu) has prompted investigation of administration schedules other than the 4-times-daily dosage commonly used with oral Bu. We have studied an allogeneic stem cell transplantation (SCT) preparative regimen comprising fludarabine (FLU) 50 mg/m2 on days -6 to -2 plus i.v. Bu 3.2 mg/kg daily in a 3-hour infusion on days -5 to -2. ⋯ Bu. This regimen incorporating once-daily i.v. Bu is convenient to give, is relatively well tolerated, gives predictable blood levels, and deserves further study in circumstances in which cytoreduction as well as immune suppression is needed.
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Biol. Blood Marrow Transplant. · Jan 2002
Clinical TrialBusulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia.
Complete bioavailability of i.v. busulfan (Bu) provides dose assurance by reducing the interdose and interpatient variability in Bu systemic exposure (Bu-SE) associated with the oral formulation. We hypothesized that Bu-SE, represented by the area under the plasma concentration versus time curve (AUC), would correlate with treatment outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for chronic myelogenous leukemia (CML). Therefore, we analyzed the risk of death, incidence of regimen-related toxicity, and incidence of acute GVHD (aGVHD) as functions of the per dose i.v. ⋯ Given the ability of i.v. Bu to provide a more consistent per-dose AUC, these results should be useful in designing future i.v. V Bu-based treatment protocols for stem cell transplantation.
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Biol. Blood Marrow Transplant. · Jan 2002
Randomized Controlled Trial Comparative Study Clinical TrialComparison of outcome of allogeneic bone marrow transplantation with and without granulocyte colony-stimulating factor (lenograstim) donor-marrow priming in patients with chronic myelogenous leukemia.
To investigate the effect of granulocyte colony-stimulating factor (G-CSF) donor-marrow priming on hematopoietic recovery and clinical outcome after allogeneic hematopoietic stem cell transplantation, we compared HILA-matched related marrow transplantation with and without G-CSF donor priming in a prospective randomized study for a homogeneous group of chronic myelogenous leukemia (CML) patients. Fifty patients (aged 12-41 years) with CML were enrolled in the study. Thirty-two patients (study group) received the marrow grafts primed with G-CSF at 3 to 4 micro/kg per day for 7 days prior to the marrow harvest, and 18 patients (control group) received the marrow grafts without G-CSF priming. ⋯ There were no significant differences in chronic GVHD (24% versus 33.3%), relapse rates (12.5% versus 11.1%), and overall survival rates (78.1% versus 66.7%, P = .32) between the study and control groups during a median follow-up period of 24 months (range, 6-50 months). There was, however, a trend in favor of improved chronic GVHD and disease-free survival in the study group. We conclude that G-CSF donor-marrow priming accelerates both neutrophil and platelet engraftment and is associated with a very low incidence of grades II to IV acute GVHD in CML patients after HLA-matched sibling marrow transplantation.
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Biol. Blood Marrow Transplant. · Jan 2002
Multicenter Study Comparative Study Clinical TrialIntravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality.
Hepatic venoocclusive disease (HVOD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) and is a well-recognized dose-limiting toxicity of oral busulfan (Bu)-based preparative regimens. The unpredictable absorption of oral Bu from the gastrointestinal (GI) tract and hepatic first-pass effects have led to the development of an intravenous Bu preparation (i.v. Bu). ⋯ Bu was the strongest predictor for development of HVOD (odds ratio, 7.5; 95% confidence interval, 2.1-27.2; P = .002). This study showed that the incidence rate of HVOD is significantly lower (P = .002) and the 100-day survival rate significantly higher (P = .002) in patients treated with i.v. Bu than in patients treated with oral Bu when Bu is used as part of a BuCy2 preparative regimen for allogeneic HSCT.
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Biol. Blood Marrow Transplant. · Jan 2002
Clinical TrialConditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study.
Busulfan (Bu) is commonly used as a component of conditioning regimens for hematopoietic stem cell transplantation. Precise delivery of the oral formulation is compromised by erratic gastrointestinal absorption. An IV Bu formulation was developed to provide dose assurance and complete bioavailability. ⋯ Treatment-related mortality at 100 days was 9.8% (6/61). Bu pharmacokinetics after IV drug administration demonstrated high inter- and intrapatient consistency; 86% of patients maintained an area under the curve between 800 and 1500 microMol-min. In conclusion, the IV Bu in this regimen was very well tolerated and demonstrated excellent antitumor efficacy, most likely because of dose assurance with predictable pharmacokinetics.