Osteonecrosis in children with acute lymphoblastic leukemia at initial diagnosis and prior to any chemotherapy.

Osteonecrosis (ON) is a common and debilitating side effect of anti-leukemic treatment in children with acute lymphoblastic leukemia (ALL). However, the impact of leukemia itself on ON development remains elusive. We analyzed 76 children enrolled in the ongoing OPAL trial, who had magnetic resonance imaging (MRI) studies at diagnosis. MRI screening revealed 14 osteonecrotic lesions (5 × hips, 9 × knees) of any grade (I-III) in 7 (9.2%) patients. Six months on, the number of ON per patient increased (1 patient), remained constant (2), and decreased (2). The severity increased from grade I to II in two patients, remained constant (1), completely resolved (2), and decreased from grade III to osteoedema (1). No differences between adolescents initially presenting with/without ON were observed concerning age, pubertal stage, body mass index, leukemia characteristics, and clinical presentation. In MRI screening, a remarkable number of adolescents with ALL present with ON at diagnosis. The course of these ON remains highly unpredictable.

Osteonecrosis develops independently from radiological leukemic infiltration of bone in adolescents with acute lymphoblastic leukemia - first findings of the OPAL trial.

Osteonecrosis (ON) is a debilitating side effect of anti-leukemic treatment. Thus far, the role of leukemic infiltration (LI) of bone is unclear. The first 30 children aged ≥10 years, who were enrolled in the ongoing OPAL trial and had MRI studies at diagnosis and at 6 months, were analyzed. MRI revealed extensive LIs in 24 (80%) patients. The signal abnormalities changed back to a physiological signal in 29 out of 30 children at 6 months. Of the 24 children with LIs at diagnosis, 3 (12.5%) developed ON ≥ II, whereas 4 (66.7%) patients without LIs subsequently developed ON ≥ II (p = .016). No differences between children initially presenting with/without LIs were observed concerning age, pubertal stage, white blood count, immunophenotype, and clinical presentation. Initial radiological LI of bone and, thus, single MRI at diagnosis cannot identify children at high risk of developing radiological ON at 6 months into treatment.

Osteonecrosis in children and adolescents with acute lymphoblastic leukemia: a therapeutic challenge.

Osteonecrosis (ON) represents one of the most common and debilitating sequelae of antileukemic treatment in children and adolescents with acute lymphoblastic leukemia (ALL). Systematic screening strategies can focus on early detection and intervention to prevent ON from progressing to stages associated with pain and functional impairment. These strategies hold promise for reducing ON-associated morbidity without the risk of impairing leukemia control. Herein, we critically reviewed clinical data on pharmacological, nonpharmacological/nonsurgical, and surgical (including cellular) treatment options for ON, which are covered in the literature and/or are conceivable based on the supposed underlying ON pathophysiology. Prevention of ON progression is of paramount importance, and attempts seem to be more effective in early (precollapse) disease status than in late-stage (collapse) ON. Based on the results of ongoing prospective magnetic resonance imaging screening studies, which will hopefully identify those patients with a high risk of ON progression and debilitating sequelae, prospective interventional studies are urgently needed. Although there is still a lack of high-quality studies, based on currently available data, core decompression surgery combined with cellular therapies (eg, employing mesenchymal stem cells) appears most promising for preventing joint infraction in children at high risk of developing late-stage ON.