Hematopoietic Stem Cell Transplantation Based on Pharmacokinetic and Pharmacodynamic Modeling

Determination of Optimal Busulfan Dose Using Pharmacokinetic Modeling in Hematopoietic Stem Cell Transplantation

In this study the investigators plan to develop a method to determine optimal busulfan dose through pharmacokinetic study.

Busulfan is a highly toxic drug with narrow therapeutic window used for the conditioning of hematopoietic stem cell transplantation. High exposure is associated with systemic toxicity such as veno-occlusive disease (VOD) and underexposure is associated with graft failure or relapse. In this study we plan to develop a method to determine optimal busulfan dose through pharmacokinetic study.

Inclusion Criteria:

1. Hematopoietic stem cell transplantation with busulfan based conditioning
2. Age: no limits.
3. Performance status: ECOG 0-2.
4. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases. 1. Heart: a shortening fraction > 30% and ejection fraction > 45%. 2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal. 3. Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.
5. Patients must lack any active viral infections or active fungal infection.
6. Appropriate donor is available: Matched in 6/6 of A, B, DR loci.
7. Patients (or one of parents if patients age < 19) should sign informed consent.

Exclusion Criteria:

1. Pregnant or nursing women.
2. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
3. Psychiatric disorder that would preclude compliance.