Novel therapy may prevent osteonecrosis in pediatric ALL
An alternate-week treatment regimen of dexamethasone significantly reduced osteonecrosis compared with standard continuous therapy among children and adolescents with acute lymphoblastic leukemia, according to study results.
Treatments for ALL, although successful in more than 80% of children and adolescents, have been linked to disproportionate rates of symptomatic osteonecrosis in adolescents. In the current study, researchers examined whether a modified dose of dexamethasone could decrease incidence of this complication.
Researchers evaluated 2,056 patients aged 1 to 21 years. Eligible participants had newly diagnosed high-risk ALL. Eligibility criteria included age ≥10 years, white blood cell count ≥50×109/L or both.
Patients were assigned to either a novel alternate-week schedule of dexamethasone (10 mg/m2 per day on days 0-6 and 14-20) or the standard continuous regimen (10 mg/m2 per day on days 0-20). The regimens were computer-generated and randomized and included permuted blocks with a double delayed intensification phase for the novel regimen and a single delayed intensification phase for the standard regimen. Protocols called for an intention-to-treat analysis.
Diagnosis of symptomatic osteonecrosis occurred in 377 confirmed skeletal sites in 143 patients, and 139 surgeries were performed.
The overall cumulative incidence of osteonecrosis at 5 years was 7.7%. This correlated with age at ALL diagnosis, with the incidence rate at 1% among patients aged 1 to 9 years; 9.9% among those aged 10 to 15 years (HR=10.4); and 20% among those aged 16 to 21 years (HR=22.2).
Researchers also observed a correlation with sex of patients aged 10 to 21 years, with osteonecrosis occurring in 15.7% of girls and 9.3% of boys (HR=1.7) in that age group.
Alternate-week treatment during phases of delayed intensification compared with standard therapy was linked to significant reductions in osteonecrosis among patients aged 10 years and older who had a rapid response to induction therapy (8.7% vs. 17%; HR=2.1). This effect was more dramatic among patients aged 16 years or older (11.3% vs. 37.5%; P=.0003). Also in this older age group, novel therapy during delayed intensification was more effective than standard treatment in girls (17.2% vs. 43.9%; P=.05) and boys (7.7% vs. 34.6%; P=.0014).
“Alternate-week dexamethasone during delayed intensification phases, a simple dose modification, reduces the risk of osteonecrosis in children and adolescents given intensified treatment for high-risk ALL,” the researchers concluded.