THE ROLE OF THERAPEUTIC DRUG MONITORING OF INTRAVENOUS BUSULFAN FOR PREVENTION OF SINUSOIDAL OBSTRUCTION SYNDROME IN CHILDREN
Objective: Busulfan is a widely used alkylating drug for conditioning of hematopoietic stem cell transplantation (HSCT). Higher exposure of Bu is associated with toxicity and (sinusoidal obstruction syndrome) SOS, whereas lower exposure is associated with graft failure or relapse risk. Therapeutic d...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Elsevier
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/fa589eab85c64341a65175faae1192f6 |
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| Sumario: | Objective: Busulfan is a widely used alkylating drug for conditioning of hematopoietic stem cell transplantation (HSCT). Higher exposure of Bu is associated with toxicity and (sinusoidal obstruction syndrome) SOS, whereas lower exposure is associated with graft failure or relapse risk. Therapeutic drug monitoring (TDM) has been recommended to overcome these issues. We aimed in this study to compare HSCT outcomes in children with and without TDM of Bu. Methodology: This retrospective study conducted at our Transplantation Unit between 2012 and 2021. Patients aged 0-18 y underwent HSCT who received Bu-based conditioning and completed post-transplant +100 days included in the study. Data were collected including demographic information, primary diagnoses, conditioning regimen, graft-related data, dose of Bu, time to neutrophil and platelet engraftment, presence of SOS, acute or chronic GvHD, and clinical outcomes. SPSS 18.0 was used for statistical analysis. Results: 172 patients (59 girls, 113 boys) with a median age of 4.70 years (IQR 2.41-10.01) were enrolled in the study. TDM of Bu was performed in 126 patients. 32 patients (19%) developed moderate or severe SOS. Incidence of SOS was significantly higher in the group without TDM. A multivariable analysis showed that presence of acute GVHD and 2 or more alkylating agents in conditioning regimen were associated were SOS. HSCT related outcomes, relapse, OS and EFS did not different between two groups. Conclusion: To improve treatment outcomes of Bu, TDM and dose adjustment, following the first dose, has highly recommended regardless of the dosing guideline was used. We also demonstrated the incidence of SOS decreased in patients with TDM, but other HSCT related outcomes were not influenced. Optimal cumulative Bu exposure canbalance between efficacy and toxicity of HSCT in children. |
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