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← Childhood Acute Lymphoblastic Leukemia

HEALTH PROFESSIONAL · SOURCE READING

Osteonecrosis

Source: Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Health Professional Version, National Cancer Institute.

Source updated: April 21, 2025 · Captured 2026-09-09.

Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary.

Context: Postinduction Treatment for Specific ALL Subgroups / Adolescents and Young Adults With ALL / Treatment options for adolescents and young adults with ALL

Adolescents with ALL appear to be at higher risk than younger children for developing therapy-related complications, including osteonecrosis, deep venous thromboses, and pancreatitis.[50,65,66] Before the use of postinduction intensification for treatment of ALL, osteonecrosis was infrequent. The improvement in outcome for children and adolescents aged 10 years and older was accompanied by an increased incidence of osteonecrosis.

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The weight-bearing joints are affected in 95% of patients who develop osteonecrosis and operative interventions were needed for management of symptoms and impaired mobility in more than 40% of cases. Most cases are diagnosed within the first 2 years of therapy and the symptoms are often recognized during maintenance.

Evidence (osteonecrosis):

In the CCG-1961 high-risk ALL study, alternate-week dosing of dexamethasone was compared with standard continuous dexamethasone during delayed intensification to determine whether the osteonecrosis risk could be reduced.[65]

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In the CCG-1961 high-risk ALL study, alternate-week dosing of dexamethasone was compared with standard continuous dexamethasone during delayed intensification to determine whether the osteonecrosis risk could be reduced.[65]

The median age at symptom onset was 16 years.

In the CCG-1961 high-risk ALL study, alternate-week dosing of dexamethasone was compared with standard continuous dexamethasone during delayed intensification to determine whether the osteonecrosis risk could be reduced.[65]

The cumulative incidence was higher in adolescents and young adults aged 16 to 21 years (20% at 5 years) than in those aged 10 to 15 years (9.9%) or in patients aged 1 to 9 years (1%).

In the CCG-1961 high-risk ALL study, alternate-week dosing of dexamethasone was compared with standard continuous dexamethasone during delayed intensification to determine whether the osteonecrosis risk could be reduced.[65]

Operative interventions were needed for management of symptoms and impaired mobility in more than 40% of cases.

In the CCG-1961 high-risk ALL study, alternate-week dosing of dexamethasone was compared with standard continuous dexamethasone during delayed intensification to determine whether the osteonecrosis risk could be reduced.[65]

The use of alternate-week dosing of dexamethasone as compared with standard continuous dexamethasone during delayed intensification in CCG-1961 reduced the risk of osteonecrosis. The greatest impact was seen in females aged 16 to 21 years, who showed the highest incidence of osteonecrosis with standard therapy containing continuous dexamethasone; osteonecrosis was reduced with alternate-week dexamethasone postinduction (57.6% to 5.6%).

In the COG AALL0232 (NCT00075725) high-risk ALL trial, patients were randomly assigned during induction to receive either 14 days of dexamethasone or 28 days of prednisone.[67]

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In the COG AALL0232 (NCT00075725) high-risk ALL trial, patients were randomly assigned during induction to receive either 14 days of dexamethasone or 28 days of prednisone.[67]

The incidence of osteonecrosis in patients older than 10 years who received dexamethasone was 24.3%, compared with an incidence of 15.9% in those who received prednisone (P = .001).

In the COG AALL0232 (NCT00075725) high-risk ALL trial, patients were randomly assigned during induction to receive either 14 days of dexamethasone or 28 days of prednisone.[67]

For patients aged 10 years and older, there was no difference in outcome between arms by corticosteroid (5-year EFS rate, 73.1% on the dexamethasone arm and 73.9% on the prednisone arm; P = .78).

In the COG AALL0232 (NCT00075725) high-risk ALL trial, patients were randomly assigned during induction to receive either 14 days of dexamethasone or 28 days of prednisone.[67]

However, among all patients in the analysis cohort, patients with osteonecrosis had superior 5-year EFS and OS rates than patients without osteonecrosis (EFS rates, 89.8% vs. 77.8%, P < .0001; OS rates, 95.8% vs. 86.1%, P < .0001).[68] Similar differences were seen in patients older than 10 years. Improved survival was directly attributed to reduced relapse rates.

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