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 continued...
Treatment options under clinical evaluation for adolescent and young adult patients with ALL
Treatment options under clinical evaluation include the following:
COG-AALL0434 (NCT00408005) (Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell ALL or T-cell Lymphoblastic Lymphoma): This is a phase III trial for patients aged 1 to 30 years with T-cell ALL utilizing a modified augmented BFM regimen. Patients are classified into one of three risk groups (low, intermediate, or high) based on NCI age/leukocyte criteria, CNS status at diagnosis, morphologic marrow response on days 15 and 29, and MRD level at day 29. The following are objectives of the trial: (1) to determine the safety and efficacy of adding nelarabine to the modified augmented BFM regimen in high- and intermediate-risk patients, (2) to determine the relative safety and efficacy of high-dose versus Capizzi methotrexate during interim maintenance, and (3) to test the efficacy of treating low-risk T-cell ALL patients without cranial radiation.
COG-AALL1131 (Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk ALL): The COG-AALL1131 protocol for patients with high-risk B-precursor ALL includes a randomized comparison of triple intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) with intrathecal methotrexate, with the objective of determining whether triple intrathecal chemotherapy reduces CNS-relapse rates and improves overall EFS. Patients with very high-risk disease include those who, at diagnosis:
- Are aged 13 years or older.
- Have 0.01% or more detectable MRD at end induction.
- Have CNS3 disease.
- Have iAMP21.
- Have severe hypodiploidy, and/or
- Have an M3 marrow on day 29 (induction failure).
These patients are eligible for a three-arm study designed to assess the efficacy of either clofarabine/etoposide/cyclophosphamide versus cyclophosphamide/etoposide versus the standard cyclophosphamide/thioguanine/cytarabine combination during the consolidation and late intensification phases.
Philadelphia Chromosome-positive ALL
Philadelphia chromosome-positive (Ph+) ALL is seen in about 3% of pediatric ALL cases, increases in adolescence, and is seen in 15% to 25% of adults. In the past, this subtype of ALL has been recognized as extremely difficult to treat with poor outcome. In 2000, an international pediatric leukemia group reported a 7-year EFS of 25%, with an OS of 36%. In 2010, the same group reported a 7-year EFS of 31% and an overall survival of 44% in Ph+ ALL patients treated without tyrosine kinase inhibitors. Treatment of this subgroup has evolved from emphasis on aggressive chemotherapy, to bone marrow transplantation, and currently to combination therapy using chemotherapy plus tyrosine kinase inhibitor.