Who can enter
• All children receiving a stem cell transplantation with busulfan as part of the conditioning
Goal
In this study we use a new method to calculate the dose of the drug busulfan. The new method is based on DNA. The goal of this study is to determine whether the first-day busulfan blood concentration is closer to the desired target as compared to regular dosing. The overarching goal is to make smaller dose adjustments during the next dosing days.
Background
Busulfan is a drug given in the days before a stem cell transplant. We know that the amount of busulfan in the blood is very important. It reduces the chance of leukemia coming back and the chance of serious side effects. Some children break down busulfan faster than others. Therefore, the amount of busulfan in the blood varies greatly among children, while the optimal amount in the blood is very important (not too little, not too much).
We know that information about genes (DNA) predicts how a patient processes busulfan in the body. A method has already been developed that calculates the first dose based on the information of the patient's DNA. We want to investigate whether a new way of determining the first dose ensures that the amount of busulfan after the first dose is immediately better.
At least 10 days before the stem cell transplant, we will take cheek mucosa using a cotton swab. We look in the cheek mucosa for the piece of DNA that causes the breakdown of busulfan.
For this study, we will randomly divide children into two groups:
- Group 1: The children in this group will receive the standard dose of busulfan.
- Group 2: The children in this group receive the first dose of busulfan determined by the child's DNA information.
In all children, we take a small amount of blood five times after the first dose. We measure the amount of busulfan in these tubes. We then adjust the 2nd, 3rd and 4th dose of busulfan to get the optimal amount of busulfan in the blood. The collection of these 5 tubes is standard practice and is done also when a child does not participate in the study.
Busulfan has been used in stem cell transplantation for decades, we already know quite a lot about this drug. For example, we know that it is important to monitor the amount in the blood. This way, we can adjust the dosage to get just the right amount: too much and too little is not good.
In this study, cheek mucosa is taken with a cotton swab. In this, your DNA is determined which determines how fast you break down busulfan. Otherwise, all procedures are the same as normal. Because we measure busulfan in everyone and adjust the dose accordingly, the final amount will not differ. In this study, we will see whether less adjustment of the dosage is required.