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 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.
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Biol. Blood Marrow Transplant. · Jan 2002
Clinical TrialEvaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation.
Intravenous busulfan (i.v. BU) has demonstrated safety when administered at 0.8 mg/kg per dose i.v. every 6 hours x 16 doses. We evaluated the safety and pharmacokinetics (PK) of giving the same total daily i.v. ⋯ The change in dosing schedule did not increase toxicity or end-organ damage despite higher plasma concentration-times. Although further study for long-term efficacy is warranted, i.v. BU can be given safely with reproducible results on a twice-daily divided or single-daily dosing schedule to patients undergoing HSCT.
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Biol. Blood Marrow Transplant. · Jan 2002
Clinical TrialTransplantation of ex vivo expanded cord blood.
Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. ⋯ At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.
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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
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.