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，可累及1%~10%的年轻患者，并引发长期病残。近十年来，磁共振成像（Magnetic Resonance Imaging, MRI）的广泛应用使得该病的早期检出与精准评估成为可能。本研究回顾性纳入法国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129例有症状的ON患者（占比2.5%），对其临床特征与MRI表现展开分析。本研究针对ON的危险因素、多灶性受累情况、MRI检出的严重病变以及患者生活质量（Quality of Life, QoL）相关数据进行了系统分析。结果显示，ON患者在确诊AL时的年龄往往大于10岁（比值比[OR]：22.46；P<10⁻⁶）、为女性（OR：1.8；P=0.002），或曾因白血病复发接受治疗（OR：1.81；P=0.041）；此类患者更易出现其他后遗症（P<10⁻⁶）。多数坏死病变累及负重关节，且69%的病例为多灶性受累。对39例患者的MRI影像进行双盲阅片后发现，其中14例存在严重病变，且多累及髋关节。青少年与成年ON患者的生活质量较差，且在发病后会受到永久性影响。综上，确诊AL时年龄大于10岁、女性性别以及曾发生复发是多灶性ON的危险因素；MRI可在三分之一的纳入患者中检出严重ON；且ON与多维度持续低下的生活质量显著相关。未来的研究应纳入针对ON管理的前瞻性数据，并致力于识别可用于针对性筛查的遗传标志物，以实现ON的早诊早治。