Precision myeloablation with TDM-guided busulfan in pediatric primary immunodeficiencies: a real-world study of 28 patients.
Pediatric immunodeficiency transplant patients had 96.4% two-year survival with therapeutic drug monitoring-guided busulfan conditioning.
Precision myeloablation with TDM-guided busulfan in pediatric primary immunodeficiencies: a real-world study of 28 patients.
Optimizing busulfan (Bu) exposure is critical for balancing engraftment and toxicity in pediatric patients with primary immunodeficiencies (primary immunodeficiencies) undergoing hematopoietic stem cell transplantation (hematopoietic stem cell transplantation).
This study evaluates the outcomes of a therapeutic drug monitoring (therapeutic drug monitoring)-guided, personalized Bu/fludarabine (Flu) regimen.
We retrospectively analyzed 28 pediatric primary immunodeficiencies patients [11 severe combined immunodeficiency (severe combined immunodeficiency) and 17 with non-severe combined immunodeficiency] who underwent first allogeneic hematopoietic stem cell transplantation (allo-hematopoietic stem cell transplantation) between March 2022 and September 2025.
Only 11/28 patients (39.3%) achieved target AUC after the first Bu dose, confirming the necessity of therapeutic drug monitoring.
Severe regimen-related toxicity was minimal: grade 3-4 mucositis (n=1, 3.5%) and definite veno-occlusive disease (veno-occlusive disease) (n=1).
Chronic graft-versus-host disease (cGVHD) occurred in 7/27 patients (25.9%), predominantly pulmonary-limited.
Cytomegalovirus (cytomegalovirus) reactivation occurred in 11 patients (39.2%) without cytomegalovirus disease.
A risk-adapted, therapeutic drug monitoring-guided Bu/Flu conditioning regimen achieves an optimal balance between efficacy and toxicity in pediatric primary immunodeficiencies hematopoietic stem cell transplantation.
With a 2-year OS of 96.4%, minimal severe regimen-related toxicity, and universal intravenous immunoglobulin (intravenous immunoglobulin) independence by 12 months, this precision myeloablative approach should be considered the preferred standard for this vulnerable population.