Acute neurotoxicity in children with B-lineage acute lymphoblastic leukemia (B-ALL) treated with intermediate risk protocols

Background. This study describes the incidence of acute neurotoxicity (NT) in children with B-lineage acute lymphoblastic leukemia (ALL) treated with three intermediate risk protocols that differ in the intensity of central n ervous system (CNS) "prophylaxis." Procedure. A total of 122 patients (64 b oys: median age 5.3 years) with B-lineage ALL without CNS leukemia diagnose d between February 1987 and December 1997 were enrolled in the intermediate risk (IR) protocols: Associazione Italiana di Ematologia ed Oncologia Pedi atrica (AIEOP)-ALL 87 (n = 33), 91 (n = 51), and 95 (n = 38). Presymptomati c CNS therapy consisted of intrathecal methotrexate (six doses) and cranial irradiation (18 Cy) in the IR AIEOP 87 study, and extended triple intrathe cal therapy with methotrexate, cytarabine, and prednisone depending on age in the IR AIEOP-ALL 91 and 95 protocols (20 and 17 total doses, respectivel y). World Health Organization (WHO) grade 4 acute neurotoxicity criteria we re employed. Patients with neurologic symptoms, in addition to physical exa mination, underwent EEG, computed tomography (CT) and/or magnetic resonance imaging (MRI), and lumbar puncture to exclude CNS leukemia and infection. Results. Acute NT was not reported in AIEOP-ALL 87 treated patients, but we observed acute NT in 3 out of 51 (5.8%) AIEOP-ALL 91 patients, and in 7 ou t of 38 (18.4%) AIEOP-ALL 95 patients. Conclusions. There was an increased incidence of acute NT in our patients with ALL treated with current interme diate risk protocols. The intensification of treatment, however, bettered e vent free survival (EFS) to 58%, 72% and 85% in IR AIEOP 87, 91 and 95 stud ies, respectively. (C) 2000 Wiley-Liss, Inc.