Adolescent Patients with ALL
Older children and adolescents (>10 years) with ALL more frequently present with adverse prognostic factors at diagnosis, including T-cell immunophenotype and Philadelphia chromosome-positivity, and have a lower incidence of favorable cytogenetic abnormalities.[25,26] These patients have a less favorable outcome than children aged 1 to 9 years at diagnosis, and more aggressive treatments are generally employed. A study from France of patients aged 15 to 20 years and diagnosed between 1993 and 1999, demonstrated superior outcome for patients treated on a pediatric trial (67%; 5-year EFS) compared with patients treated on an adult trial (41%; 5-year EFS).
Other studies have confirmed that older adolescent patients and young adults fare better on pediatric rather than adult regimens.[26,29,30,31]; [Level of evidence: 2A] For instance, the DFCI ALL Consortium reported a 5-year EFS of 78% in adolescents aged 15 to 18 years in a pediatric trial. In the COG high-risk study (CCG-1961), the 5-year EFS rate for patients aged 16 to 21 years was 71.5%.[Level of evidence: 1iiDi] For rapid responders randomized to early intensive postinduction therapy on the augmented intensity arms of this study, the 5-year EFS rate was 82%. In a SJCRH study, 44 adolescents aged 15 to 18 years had an EFS of approximately 85% � 5%. Also, in a Spanish study, adolescents (aged 15-18 years) and young adults (aged 19-30 years) with standard risk ALL were treated with a pediatric-based regimen.[Level of evidence: 2A] The complete remission rate was 98%, EFS rate was 61%, and overall survival rate was 69%, with no differences in outcome between adolescents and young adults. Given the relatively favorable outcome that can be obtained in these patients with chemotherapy regimens used for pediatric ALL, there is no role for the routine use of allogeneic SCT in first remission for adolescents and young adults with ALL.
The reason that adolescents and young adults achieve superior outcomes with pediatric regimens is not known, although possible explanations include treatment setting (i.e., site experience in treating ALL), adherence to protocol therapy, and the components of protocol therapy. Adolescents with ALL appear to be at higher risk than younger children for developing therapy-related complications, including osteonecrosis, deep venous thromboses, and pancreatitis.[26,35,36,37] High body mass index is also a risk factor for osteonecrosis, and may be associated with a higher relapse rate in older patients.
Treatment options under clinical evaluation
The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
COG-AALL0434: 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 objectives of the trial are (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.
CALGB-10403: This is a phase II trial for adolescent and young adults aged 15 to 40 years with newly diagnosed ALL (B-cell or T-cell) treated with a regimen that is nearly identical to the Capizzi methotrexate arm of the COG-AALL0232 trial and treated by adult hematologists/oncologists at multiple sites.
OSU-08066: DFCI protocol 06-254 (OSU-08066) is a phase II trial conducted by the DFCI ALL Consortium for patients aged 18 to 50 years with newly diagnosed ALL. The treatment regimen is identical to the very high-risk arm on the pediatric DFCI protocol, DFCI-05001, and includes 30 weeks of postinduction consolidation with intravenous PEG-asparaginase (given every 2 weeks). Older adolescents (aged 15-18 years) are treated on pediatric protocol DFCI-05001 as high-risk patients.