Bone mineral density in children with acute lymphoblastic leukemia.
Cancer
; 124(5): 1025-1035, 2018 03 01.
Article
en En
| MEDLINE
| ID: mdl-29266176
ABSTRACT
BACKGROUND:
Children with acute lymphoblastic leukemia (ALL) can develop reduced bone mineral density (BMD). However, data from patients who received treatment on a frontline regimen without cranial irradiation are limited, and no genome-wide analysis has been reported.METHODS:
Lumbar BMD was evaluated by quantitative computed tomography at diagnosis, after 120 weeks of continuation therapy, and after 2 years off therapy in pediatric patients with ALL (ages 2-18 years at diagnosis) who were treated on the St. Jude Total XV Protocol. Clinical, pharmacokinetic, and genetic risk factors associated with decreased BMD Z-scores were evaluated.RESULTS:
The median BMD Z-score in 363 patients was 0.06 at diagnosis, declined to -1.08 at week 120, but partly recovered to -0.72 after 2 years off therapy; BMD in patients with low BMD Z-scores at diagnosis remained low after therapy. Older age (≥10 years vs 2-9.9 years at diagnosis; P < .001), a higher BMD Z-score at diagnosis (P = .001), and a greater area under the plasma drug concentration-time curve for dexamethasone in weeks 7 and 8 of continuation therapy (P = .001) were associated with a greater decrease in BMD Z-score from diagnosis to week 120. Single-nucleotide polymorphisms in 2 genes important in osteogenesis and bone mineralization (COL11A1 [reference single-nucleotide polymorphism rs2622849]; P = 2.39 × 10-7 ] and NELL1 [rs11025915]; P = 4.07 × 10-6 ]) were associated with a decreased BMD Z-score. NELL1 (P = .003) also was associated with a greater dexamethasone area under the plasma drug concentration-time curve.CONCLUSIONS:
BMD Z-scores decreased during therapy, especially in patients who had clinical, pharmacokinetic, and genetic risk factors. Early recognition of BMD changes and strategies to optimize bone health are essential. Cancer 2018;1241025-35. © 2017 American Cancer Society.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Densidad Ósea
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudio:
Guideline
/
Risk_factors_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Cancer
Año:
2018
Tipo del documento:
Article