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

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

Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] Guide

• General Information About Childhood Acute Lymphoblastic Leukemia (ALL)
• Risk-based Treatment Assignment
• Treatment Option Overview for Childhood ALL
• Treatment for Newly Diagnosed Childhood ALL
• Postinduction Treatment for Childhood ALL
• CNS-directed Therapy for Childhood ALL
• Postinduction Treatment for Specific ALL Subgroups
• Treatment of Relapsed Childhood ALL
• Changes to this Summary (05 / 02 / 2014)
• About This PDQ Summary
• Get More Information From NCI

The benefit of using dexamethasone in children aged 10 to 18 years requires further investigation because of the increased risk of steroid-induced osteonecrosis in this age group.[21,54]

Duration of maintenance therapy

Maintenance chemotherapy generally continues until 2 to 3 years of continuous CR. On some studies, boys are treated longer than girls;[13] on others, there is no difference in the duration of treatment based on gender.[11,17] It is not clear whether longer duration of maintenance therapy reduces relapse in boys, especially in the context of current therapies.[17][Level of evidence: 2Di] Extending the duration of maintenance therapy beyond 3 years does not improve outcome.[48]

Adherence to maintenance therapy

Nonadherence to treatment with 6-MP in maintenance is associated with a significant increase in the risk of relapse.[35]

Evidence (adherence to treatment):

1. The COG studied the impact of non-adherence to 6-MP during maintenance in 327 children and adolescents of different ethnic backgrounds.[35]
   • Adherence declined from 95% to 90% over the 6-month observation period.
   • Adherence was significantly lower among Hispanics, patients older than 12 years, and patients from single-mother households.
   • Lower adherence to 6-MP was associated with a significantly higher risk of relapse. After adjusting for other prognostic factors (including NCI risk group and chromosomal abnormalities), a progressive increase in relapse was observed with decreasing adherence.

Treatment options under clinical evaluation

Risk-based treatment assignment is a key therapeutic strategy utilized for children with ALL, and protocols are designed for specific patient populations that have varying degrees of risk of treatment failure. The Risk-based Treatment Assignment section of this summary describes the clinical and laboratory features used for the initial stratification of children with ALL into risk-based treatment groups.

Ongoing clinical trials include the following:

COG studies for B-precursor ALL

Standard-risk ALL

1. COG-AALL0932 (Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk ALL):
   This trial subdivides standard-risk patients into two groups: low risk and average risk. Low risk is defined as the presence of all of the following: NCI-standard risk age/WBC, favorable genetics (e.g., double trisomies or ETV6-RUNX1), CNS1 at presentation, and low MRD (<0.01% by flow cytometry) at day 8 (peripheral blood) and day 29 (marrow). Average risk includes other NCI standard-risk patients excluding those with high day 29 MRD morphologic induction failure or other unfavorable presenting features (e.g., CNS3, iAMP21, low hypodiploidy, MLL translocations, and BCR-ABL).
   
   All patients will receive a three-drug induction (dexamethasone, vincristine, and IV PEG-L-asparaginase) with intrathecal chemotherapy. For postinduction therapy, low-risk patients will be randomly assigned to receive one of the following:
   
   • A regimen based on POG-9904, including six courses of intermediate-dose methotrexate (1 g/m²) but without any alkylating agents or anthracyclines.
   • A modified BFM backbone including two interim maintenance phases with escalating doses of IV methotrexate (no leucovorin) and one delayed intensification phase.
   
   The objective is not to prove superiority of either regimen, but rather, to determine whether excellent outcomes (at least 95% 5-year DFS) can be achieved.
   
   All average-risk patients will receive a modified BFM-backbone as postinduction treatment. For these patients, the study is comparing, in a randomized fashion, two doses of weekly oral methotrexate during the maintenance phase (20 mg/m² and 40 mg/m²) to determine whether the higher dose favorably impacts DFS. Average-risk patients are also eligible to participate in a randomized comparison of two schedules of vincristine/dexamethasone pulses during maintenance (delivered every 4 weeks or every 12 weeks). The objective of this randomization is to determine whether vincristine/dexamethasone pulses can be delivered less frequently without adversely impacting outcome.