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

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 <i>child and adolescent leukemias</i>) cohort (<i>n</i> = 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 &gt;10 years old at the time of AL diagnosis (odds ratio [OR]: 22.46; <i>p</i> &lt; 10⁻⁶), female (OR: 1.8; <i>p</i> = 0.002), or treated for relapse (OR: 1.81; <i>p</i> = 0.041). They more frequently suffered from other sequelae (<i>p</i> &lt; 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 &gt;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.

骨坏死（Osteonecrosis, ON）是急性白血病（acute leukemia, AL）治疗中已知的并发症，会影响1%~10%的年轻患者，并导致长期残疾。过去十年间磁共振成像（Magnetic Resonance Imaging, MRI）的广泛应用使得骨坏死得以更早检出，并实现更精准的评估。本研究对从法国LEA（Leucémies de l’Enfant et de l’Adolescent，即儿童与青少年白血病）队列（总样本量n=4973）中回顾性招募的129例有症状骨坏死患者（占比2.5%）的临床与影像学特征展开了探究。我们分析了与骨坏死危险因素、多灶性累及、磁共振成像检出的严重病变以及患者生活质量（Quality of Life, QoL）相关的数据。骨坏死患者在急性白血病诊断时的年龄往往超过10岁（比值比[OR]=22.46；p<10⁻⁶）、为女性（OR=1.8；p=0.002）或因疾病复发接受治疗（OR=1.81；p=0.041）。他们更常出现其他后遗症（p<10⁻⁶）。多数坏死病变累及负重关节，且69%的病例为多灶性累及。对39例患者的磁共振成像影像进行双盲阅片后发现，14例存在严重病变，且多累及髋关节。青少年与成年患者的生活质量在骨坏死发作后较差且受到永久性影响。综上，急性白血病诊断时年龄＞10岁、女性性别以及疾病复发是多灶性骨坏死的危险因素；磁共振成像在三分之一的纳入患者中检出了严重骨坏死；骨坏死与多维度持续较差的生活质量相关。未来的研究应纳入针对骨坏死管理的前瞻性数据，并尝试识别可用于针对性筛查的遗传标志物，以实现骨坏死的早期检出与治疗。