Acute Lymphoblastic Leukemia in Japanese Adolescents; Biology and Toxicity Profile

In the treatment for acute lymphoblastic leukemia (ALL), adolescents were reported to have worse prognosis than children because of their treatment compliance and response. In this study, we compared clinical features, treatment toxicity and outcome between children and adolescents treated with Japan Association of Childhood Leukemia Study (JACLS) ALL-02 protocol.

The dataset of 1246 eligible patients enrolled in the study between April 2002 and May 2008 was analyzed. The patients were assigned into five categories; SR (PGR, age between 1 and 9 years, WBC<10K and no CNS disease, HR (non SR with PGR; SR with t(1;19), 11q23 other than t(4;11), or M3 marrow on day15), ER (PPR, hypodiploid, unclassified, mixed-lineage, HR with M3 marrow on day15), T (T-lineage) and F (non CR on day 33, T with M3 marrow on day15, or t(4;11)). The patients with Ph+ ALL were excluded from this analyze. The data of 249 patients older than 10 years of age (adolescent group) were compared with those of 705 aged 1 to 5 years and 292 aged 6 to 9 years. The adolescent group included 28 patients older than 15 years of age. The survival rate was estimated with Kaplan–Meier method and two –sided log-rank test using SAS version 9.1.

ETV6-RUNX1 and hyperdiploidy were significantly less frequent in adolescents. The rates of PGR and CR on day 33 in adolescents were significantly lower than those in younger patients (82.7% vs. 90.5%, p<0.01, and 93.1% vs. 97.2%, Ap<0.01, respectively). Five-year overall survival (OS) and event-free survival (EFS) for adolescents were significantly lower than those for children aged 1 to 5 years (78.9% vs. 93.9%, p<0.01, 70.9% vs. 87.5%, p<0.01, respectively). In comparison of adverse effects between adolescent and children groups treated with HR protocol, Grade III and IV neurotoxicity was more frequently observed in adolescents than younger patients (1.99% vs. 0.39%, p<0.01) while infection, pancreatitis or liver toxicity was not significantly different between the two groups.

The results indicated that poorer outcome in adolescents with ALL may not result from severe treatment toxicities, but link with some specific biology of the leukemic cells.

No relevant conflicts of interest to declare.