Symptomatic osteonecrosis in French survivors of childhood and adolescent leukemia: a clinical and MRI study of LEA cohort

Abstract

Osteonecrosis (ON) is a known complication of acute leukemia (AL) management, affecting 1%–10% of young patients and resulting in long-term morbidity. Widespread access to MRI over the past decade has allowed earlier detection and more accurate assessment. This study investigated clinical and MRI features of the 129 (2.5%) patients with symptomatic ON retrospectively recruited from the French LEA (Leucémies de l’Enfant et de l’Adolescent, or child and adolescent leukemias) cohort (n = 4,973). We analyzed data concerning ON risk factors, multifocal involvement, severe lesions detected by MRI, and patient quality of life (QoL). ON patients tended to be >10 years old at the time of AL diagnosis (odds ratio [OR]: 22.46; p < 10⁻⁶), female (OR: 1.8; p = 0.002), or treated for relapse (OR: 1.81; p = 0.041). They more frequently suffered from other sequelae (p < 10⁻⁶). Most necroses involved weight-bearing joints, and they were multifocal in 69% of cases. Double-blinded review of MRIs for 39 patients identified severe lesions in 14, usually in the hips. QoL of adolescents and adults was poor and permanently impacted after onset of ON. In conclusion, age >10 at time of AL diagnosis, female sex, and relapse occurrence were risk factors for multifocal ON; MRI revealed severe ON in a third of the patients considered; and ON was associated with persistently poor QoL affecting multiple domains. Future studies should include prospective data addressing ON management and seek to identify genetic markers for targeted screening enabling early ON detection and treatment.

Keywords:

• Children
• late effects
• leukemia
• osteonecrosis

Acknowledgments

We are grateful to all the survivors, and their families, who agreed to participate in this study. Our thanks also go to all LEA program investigators, past and present, who identified potential cohort members.

Additional information

Funding

This study was funded by the French National Clinical Research Program; the French National Cancer Institute (InCA); the French National Research Agency (ANR); the PACA Cancéropôle; the PACA Regional Council; the Hérault, Bouches-du-Rhône, Corse du Sud, Gers, and Gironde Departmental Committees of the Ligue contre le Cancer; the national office of the Ligue Contre le Cancer; and the Laurette Fugain Association.