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Engraftment failure following bone marrow transplantation in children with thalassemia major using busulfan and
H Solh1, K Rao, A Martins da Cunha
1Department of Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Insights
Allogeneic bone marrow transplantation (BMT) for beta-thalassemia major showed higher engraftment success in older children. Younger children may require adjusted busulfan (Bu) dosing for effective bone marrow ablation.
Area of Science:
- Pediatric Hematology
- Hematopoietic Stem Cell Transplantation
- Genetic Blood Disorders
Background:
- Beta-thalassemia major is a severe inherited blood disorder requiring lifelong transfusions.
- Allogeneic bone marrow transplantation (BMT) offers a potential cure but faces challenges like engraftment failure.
- Optimizing conditioning regimens is crucial for successful BMT outcomes in pediatric patients.
Purpose of the Study:
- To evaluate the efficacy and factors influencing engraftment in children with beta-thalassemia major undergoing BMT.
- To identify patient characteristics and conditioning variables associated with successful engraftment.
- To investigate the role of busulfan (Bu) dosing in relation to patient age and engraftment outcomes.
Main Methods:
- Retrospective analysis of 13 children with beta-thalassemia major undergoing BMT from HLA-matched sibling donors.
- Conditioning regimen included busulfan (Bu) at 16 mg/kg and cyclophosphamide (Cy) at 200 mg/kg.
- Statistical analysis to identify significant factors associated with engraftment success or failure.
Main Results:
- Eight out of 13 patients achieved engraftment (Group 1), with a median age of 13 years.
- Five patients failed to engraft (Group 2), with a median age of 6 years.
- Significant factors for engraftment included older patient age, longer duration of white blood cell nadir, and higher busulfan (Bu) dose adjusted for body surface area.
Conclusions:
- Engraftment in BMT for beta-thalassemia major is significantly influenced by patient age and conditioning intensity.
- Younger children may experience suboptimal busulfan (Bu) exposure, potentially leading to inadequate bone marrow ablation and engraftment failure.
- Further studies are warranted to optimize busulfan (Bu) dosing strategies based on age and body surface area to improve BMT success rates in pediatric beta-thalassemia major.
Abstract:
Thirteen children older than 3 years of age with beta-thalassemia major underwent allogeneic bone marrow transplantation (BMT) from a full human leukocyte antigen (HLA) matched sibling donor in a single institution. These patients received busulfan (Bu). 16 mg/kg followed by cyclophosphamide (Cy) 200 mg/kg for conditioning. Eight of the 13 patients (Group 1) engrafted and have a median age of 13 years (range 5-15 years). The five patients (Group 2) who failed to engraft have a median age of 6 years (range 3-8 years). The association with the following factors was found to be statistically significant: age (older in Group 1), duration of nadir of white blood count (WBC) of < or = .1 x 10(9)/L (longer in Group 1), and the dose of Bu administered to each patient calculated on the basis of body surface area (higher dose in Group 1). The high rate of engraftment failure (5 out of 13) may be related to the suboptimal systemic exposure of Bu in younger children leading to inadequate bone marrow ablation when the standard dose of 16 mg/kg is used.