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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postinduction Treatment for Specific ALL Subgroups

Table 3. Outcome According to Treatment Protocol for Adolescents and Young Adults with ALL

Site and Study GroupAdolescent and Young Adult Patients (No.)Median age (y)Survival (%)
ALL = acute lymphoblastic leukemia; EFS = event-free survival; OS = overall survival.
AEIOP = Associazione Italiana Ematologia Oncologia Pediatrica; CALGB = Cancer and Leukemia Group B; CCG = Children's Cancer Group; DCOG = Dutch Childhood Oncology Group; FRALLE = French Acute Lymphoblastic Leukaemia; GIMEMA = Gruppo Italiano Malattie e Matologiche dell'Adulto; HOVON = Dutch-Belgian Hemato-Oncology Cooperative Group; LALA = France-Belgium Group for Lymphoblastic Acute Leukemia in Adults; MRC = Medical Research Council (United Kingdom); NOPHO = Nordic Society for Pediatric Hematology and Oncology; UKALL = United Kingdom Acute Lymphoblastic Leukaemia.
United States[28]   
CCG (Pediatric)1971667, OS 7 y
CALGB (Adult)1241946
 
France[34]   
FRALLE 93 (Pediatric)771667 EFS
LALA 941001841
 
Italy[35]   
AEIOP (Pediatric)1501580, OS 2 y
GIMEMA (Adult)951671
 
Netherlands[36]   
DCOG (Pediatric)471271 EFS
HOVON442038
 
Sweden[37]   
NOPHO 92 (Pediatric)361674, OS 5 y
Adult ALL991839
 
United Kingdom[31]   
MRC ALL (Pediatric)6115–1771, OS 5 y
UKALL XII (Adult)6715–1756

Osteonecrosis

Adolescents with ALL appear to be at higher risk than younger children for developing therapy-related complications, including osteonecrosis, deep venous thromboses, and pancreatitis.[30,38] 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.

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

Evidence (osteonecrosis):

  1. In the CCG-1961 high-risk ALL study, alternate-week dosing of dexamethasone was compared with standard continuous dexamethasone during delayed intensification to see if the osteonecrosis risk could be reduced.[38]
    • The median age at symptom onset was 16 years.
    • 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%).
    • Operative interventions are needed for management of symptoms and impaired mobility in more than 40% of cases.
    • 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 16 to 21 year old females showing the highest incidence of osteonecrosis with standard therapy containing continuous dexamethasone where it was reduced with alternate-week dexamethasone postinduction (57.6% to 5.6%).
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