Related Experiment Video
Updated: Jul 12, 2026
Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice
Published on: April 1, 2015
Precision myeloablation with TDM-guided busulfan in pediatric primary immunodeficiencies: a real-world study of 28
Kaige Zhang1,2, Ximu Sun1,2, Jun Yang1,2
1Hematology Center (Stem Cell Transplantation Department), National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Background:
Optimizing busulfan (Bu) exposure is critical for balancing engraftment and toxicity in pediatric patients with primary immunodeficiencies (PID) undergoing hematopoietic stem cell transplantation (HSCT). This study evaluates the outcomes of a therapeutic drug monitoring (TDM)-guided, personalized Bu/fludarabine (Flu) regimen.
Methods:
We retrospectively analyzed 28 pediatric PID patients [11 severe combined immunodeficiency (SCID) and 17 with non-SCID] who underwent first allogeneic HSCT (allo-HSCT) between March 2022 and September 2025. All patients received Flu (150-180 mg/m2) and TDM-guided Bu with target cumulative area under the curve (AUC) of 60-70 mg·h/L for SCID and 85-95 mg·h/L for non-SCID. Primary endpoints were overall survival (OS) and event-free survival (EFS). Secondary endpoints included engraftment, regimen-related toxicity (RRT), graft-versus-host disease (GVHD), and immune reconstitution.
Results:
Only 11/28 patients (39.3%) achieved target AUC after the first Bu dose, confirming the necessity of TDM. With a median follow-up of 829.5 days [interquartile range (IQR), 376-1,046 days], 2-year OS and EFS were 96.42%. Sustained engraftment with complete or high-level donor chimerism was achieved in 96.42% of patients. Severe RRT was minimal: grade 3-4 mucositis (n=1, 3.5%) and definite veno-occlusive disease (VOD) (n=1). No grade 3-4 acute GVHD occurred. Chronic GVHD (cGVHD) occurred in 7/27 patients (25.9%), predominantly pulmonary-limited. Cytomegalovirus (CMV) reactivation occurred in 11 patients (39.2%) without CMV disease. All surviving patients discontinued immunoglobulin replacement within one year.
Conclusions:
A risk-adapted, TDM-guided Bu/Flu conditioning regimen achieves an optimal balance between efficacy and toxicity in pediatric PID HSCT. With a 2-year OS of 96.4%, minimal severe RRT, and universal intravenous immunoglobulin (IVIG) independence by 12 months, this precision myeloablative approach should be considered the preferred standard for this vulnerable population.
More Related Videos
06:08Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model
Published on: February 10, 2023
08:05Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease
Published on: March 17, 2020
