Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia.

PURPOSE: Nelarabine is effective in inducing remission in patients with relapsed and refractory T-cell acute lymphoblastic leukemia (T-ALL) but has not been fully evaluated in those with newly diagnosed disease. PATIENTS AND METHODS: From 2007 to 2014, Children's Oncology Group trial AALL0434 (ClinicalTrials.gov identifier: NCT00408005) enrolled 1,562 evaluable patients with T-ALL age 1-31 years who received the augmented Berlin-Frankfurt-Muenster (ABFM) regimen with a 2 × 2 pseudo-factorial randomization to receive escalating-dose methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX) or high-dose MTX (HDMTX) with leucovorin rescue. Intermediate- and high-risk patients were also randomly assigned after induction to receive or not receive six 5-day courses of nelarabine that was incorporated into ABFM. Patients who experienced induction failure were nonrandomly assigned to HDMTX plus nelarabine. Patients with overt CNS disease (CNS3; ≥ 5 WBCs/µL with blasts) received HDMTX and were randomly assigned to receive or not receive nelarabine. All patients, except those with low-risk disease, received cranial irradiation. RESULTS: The 5-year event-free and overall survival rates were 83.7% ± 1.1% and 89.5% ± 0.9%, respectively. The 5-year disease-free survival (DFS) rates for patients with T-ALL randomly assigned to nelarabine (n = 323) and no nelarabine (n = 336) were 88.2% ± 2.4% and 82.1% ± 2.7%, respectively (P = .029). Differences between DFS in a four-arm comparison were significant (P = .01), with no interactions between the MTX and nelarabine randomizations (P = .41). Patients treated with the best-performing arm, C-MTX plus nelarabine, had a 5-year DFS of 91% (n = 147). Patients who received nelarabine had significantly fewer isolated and combined CNS relapses compared with patients who did not receive nelarabine (1.3% ± 0.63% v 6.9% ± 1.4%, respectively; P = .0001). Toxicities, including neurotoxicity, were acceptable and similar between all four arms. CONCLUSION: The addition of nelarabine to ABFM therapy improved DFS for children and young adults with newly diagnosed T-ALL without increased toxicity.

Religiosity and Effortful Control as Predictors of Indonesian Adolescents' Tobacco and Alcohol Use: Moderation and Mediation.

Moderation and mediation models of religiosity and effortful control as predictors of tobacco and alcohol use were tested in this 2-year longitudinal study of 563 16-year-old Muslim Indonesian adolescents. Adolescents reported their effortful control, religiosity, and tobacco and alcohol use and peers provided reports of adolescents' effortful control. Although both moderation and mediation effects emerged when predicting Year 2 substance use, predictions of change from Year 1 to Year 2 substance use yielded effects of moderation for peer- but not self-reported effortful control for boys; no mediation effects emerged. These findings provide evidence of interconnections between effortful control and religiosity as predictors of substance use and suggest the need for further longitudinal studies that compare moderation and mediation models.

Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization.

PURPOSE: Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children's Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen. PATIENTS AND METHODS: COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase. All patients with T-ALL, except for those with low-risk features, received prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation during either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase. RESULTS: AALL0434 accrued 1,895 patients from 2007 to 2014. The 5-year event-free survival and overall survival rates for all eligible, evaluable patients with T-ALL were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively. The 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia were randomly assigned to receive ABFM with C-MTX (n = 519) or HDMTX (n = 512). The estimated 5-year disease-free survival ( P = .005) and overall survival ( P = .04) rates were 91.5% (95% CI, 88.1% to 94.8%) and 93.7% (95% CI, 90.8% to 96.6%) for C-MTX and 85.3% (95% CI, 81.0%-89.5%) and 89.4% (95% CI, 85.7%-93.2%) for HDMTX. Patients assigned to C-MTX had 32 relapses, six with CNS involvement, whereas those assigned to HDMTX had 59 relapses, 23 with CNS involvement. CONCLUSION: AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received CRT, with later timing for those receiving HDMTX.

Indonesian adolescents' spiritual and religious experiences and their longitudinal relations with socioemotional functioning.

The spirituality and religiosity of Indonesian Muslim adolescents were examined longitudinally as were the relations of spirituality and religiosity with (mal)adjustment. At Time 1 (T1), 959 seventh-grade Muslim adolescents were screened for selection of a sample; at Time 2 (T2), 183 eighth-grade adolescents participated; and at Time 3 (T3), 300 ninth-grade adolescents (164 new participants) participated. At T1, adolescents' peer likeability was assessed; at T2, adolescents' global and cognitive esteem were measured; and at T2 and T3, adolescents' (mal)adjustment, spirituality, and religiosity were assessed. Adolescents and parents rated aspects of (mal)adjustment, spirituality, and religiosity. Teachers also rated adolescents' (mal)adjustment. In general, we found that T2 spirituality and religiosity were positively related to T3 adjustment and negatively related to T3 maladjustment, although in panel models, support for prediction of outcomes from spirituality and religiosity was found only for loneliness and socially appropriate behavior. In addition, there was some evidence in the models that certain aspects of (mal)adjustment (self-esteem and social competence, and to a marginal degree, parent-rated internalizing problems and teacher-rated prosociality) predicted spirituality and religiosity longitudinally.

Religious involvement and the social competence and adjustment of Indonesian Muslim adolescents.

This study assessed the relation between religious involvement and multiple indices of competence in 183 eighth- and ninth-grade Indonesian Muslim adolescents (M = 13.3 years). The authors assessed spirituality and religiosity using both parent and adolescent reports, and social competence and adjustment using multiple measures and data sources. Structural equation modeling analyses revealed that parent and adolescent reports of religiosity and spirituality yielded a single religious involvement latent variable that was related to peer group status, academic achievement, emotional regulation, prosocial behavior, antisocial/problem behavior, internalizing behavior, and self-esteem. The consistency of relations between religious involvement and competence may be in part attributable to the collectivist context of religion in West Java, Indonesia, within which people exhibit strong beliefs in Islam and religion permeates daily life.