Incidence and outcome of osteonecrosis in children and adolescents after intensive therapy for acute lymphoblastic leukemia (ALL)

Abstract

Osteonecrosis (ON), a significant complication following treatment of acute lymphoblastic leukemia (ALL), has a profound impact on quality of life of ALL survivors. We studied incidence and outcome of ON in patients treated on or according to Australian and New Zealand Children's Haematology/ Oncology Group (ANZCHOG) study 8 at The Children's Hospital at Westmead. The study involved retrospective chart review of the patients. ON was defined by development of symptoms and confirmed by magnetic resonance imaging. From 2002–2011, 251 patients (143M, 108F, 59 Standard Risk (SR), 159 Medium Risk (MR) 5 High Risk (HR), and 28 Very high risk (VHR)) were treated according to study 8. Eighteen (7M, 11F, 2 SR, 12 MR, 4 VHR) patients developed ON (7.2%). Median age at diagnosis was 13.05 years(4.3–16.7). Incidence of ON in patients > 10 years at diagnosis was 29%. Six out of 18 patients developed ON after allogeneic stem cell transplantation. Median time from diagnosis to the development of ON following chemotherapy for ALL was 1.15 years (range 0.25–2.12). Most patients were treated with intravenous Zoledronic acid. At last follow‐up, three patients had undergone arthroplasty, two patients were symptom free, and the remaining 13 patients reported persistent pain with activity. A majority of patients with ON of the hips had radiological progression. Overall, 7% of patients with ALL developed ON. Age >10 years was the most important risk factor. At last follow‐up, 70% of patients had persistent symptoms. Although Zoledronic acid improved pain, most patients with ON of the hips had radiological progression.

High prevalence of osteonecrosis among the hemophagocytic lymphohistiocytosis population: Single institution 10‐year retrospective data review

“…This prevalence is similar to other diseases which require high doses of corticosteroids, such as SLE and ALL[3, 4]. Average time between diagnosis of HLH and imaging diagnosis of osteonecrosis was 17.6 months, range 8 days – 3.6 years (Table 1).…”

The Investigation of Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia

“…As reported in the literature, the risk of osteonecrosis and other bone complications was significantly higher in patients aged ≥10 years in our study. Age remains the strongest and most consistently identified factor, with patients 10 to 20 years old at greatest risk [5,6,7,8,9,10,27,33]. In a retrospective report on the ALL-BFM-95 trial, the osteonecrosis incidence was reported to be 8.9% in patients aged ≥10 years and even higher in those ≥15 years (16.7%) [9].…”

Osteonecrosis in children with acute lymphoblastic leukemia

“…[7][8][9][10][11]43,62 In contrast, the incidence is lower in adults undergoing ALL therapy. 36 Thus, the pathogenesis of osteonecrosis is likely strongly associated with factors being most prominent in adolescent age, thereby causing the highest vulnerability for osteonecrosis in this age.…”