Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study.

What was studied

This study sought the optimal busulfan exposure window in children with acute lymphoblastic leukemia (ALL). The children were having allogeneic stem cell transplant (HSCT). Data came from the ALLSCTped 2012 FORUM phase 3 trial. 145 people got fludarabine-busulfan-thiotepa conditioning. Busulfan exposure came from a pharmacokinetic model. Event-free survival (EFS) was a main outcome. So was graft-versus-host disease-free relapse-free survival (GRFS).

What they found

The window was 73.3 up to 98.0 mg.h/L. This is the cAUC, the area under the busulfan curve. People outside it had lower EFS (hazard ratio 1.93; p = 0.008). They also had lower GRFS (hazard ratio 2.01; p = 0.002). Underexposure went with more relapse (hazard ratio 1.93; p = 0.019). Overexposure went with more treatment-related toxicity and graft-versus-host disease. People with optimal exposure did as well as a comparison group. That group got total-body irradiation (TBI). The measures were EFS, GRFS, overall survival and relapse. This post hoc comparison used 51 people in each group.

What it means for patients

The authors say they found a favorable busulfan exposure window. It is for children with ALL having HSCT. They say therapeutic drug monitoring with personalized busulfan dosing improves HSCT outcomes. They say it might be validated as an alternative to irradiation.

Why it is not certain yet

The authors say the exposure window may need validation. The irradiation comparison was post hoc. Only people with busulfan levels available were included.

Source

Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study.

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