Genetic Biomarkers to Identify the Risk of Osteonecrosis in Children with Acute Lymphoblastic Leukemia

Hoed, Marissa A. H. den; Pluijm, Saskia M. F.; Uitterlinden, André G.; Pieters, Rob; Heuvel‐Eibrink, Marry M. van den

doi:10.1007/s40291-016-0226-z

Cited by 3 publications

(1 citation statement)

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“…Since not all patients exposed to the same treatment will develop ON, we can assume that pathophysiological mechanisms are underpinned by genetic polymorphisms. Some studies go in this direction, with an impact of the nucleotide polymorphisms of the plasminogen activator inhibitor 1-gene, or glutamate receptor GRIN3A 34,35 . The nested case control French GENLEA01 study (Genome-wide association studies GWAS identification of genetic factors affecting the occurrence of late side effects in childhood leukemia survivors from the L.E.A cohort) could help to solve these questions in the future.…”

Section: Discussionmentioning

confidence: 99%

Symptomatic osteonecrosis in French survivors of Childhood and Adolescent Leukemia: a clinical and radiological study from the L.E.A. program

HUAULT

Gautier

Charon

et al. 2022

Preprint

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Background. Osteonecrosis (ON) is a long-known complication of acute leukemia (AL) management affecting 1 to 10% of young patients, leading to long-term morbidity. Widespread access to Magnetic Resonance Imagery (MRI) over the past ten years has allowed earlier detection and more accurate assessment. This study investigated clinical and radiological features of ON, among the large French cohort L.E.A (Leucémie Enfant Adolescent) Procedure. Patients with ON were retrospectively enrolled and risk factors for the onset, the multifocal involvement and severe damage were analyzed. Quality of life (QoL) was also evaluated. A sub-study described radiological features. Results. 129/4973 patients developed ON (2.5%) and were preferentially aged over 10 years at time of AL diagnosis (OR 22.46, p <10-6). Females were preferentially affected (OR 1.8, p=0.002) like patients treated for relapse (OR 1.81, p=0.041). Patients presenting ON suffered more frequently from other sequelae (p<10-6). Most of the necrosis were involving weight-bearing joints and multiple joints in 69% of cases. MRI of 39 patients with ON were double blinded reviewed. Overall, 14/39 suffered from severe impairment, preferentially on hips. QoL of adolescents and adults was poor and permanently affected once ON occurred. Conclusions. Age of over 10 years at diagnosis of AL, relapse and female sex were at risk of developing ON involving preferentially multiple joints. One third was severe and lasting poor QoL impacting several domains was found. Future studies should include prospective data on management and biological genetic features to build a targeted screening program to detect and manage ON earlier.

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Section: Discussionmentioning

confidence: 99%