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

Med Pediatr Oncol. 2000 Nov;35(5):449-55. doi: 10.1002/1096-911x(20001101)35:5<449::aid-mpo2>;2-x.


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 nervous system (CNS) "prophylaxis. "

Procedure: A total of 122 patients (64 boys; median age 5.3 years) with B-lineage ALL without CNS leukemia diagnosed between February 1987 and December 1997 were enrolled in the intermediate risk (IR) protocols: Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL 87 (n = 33), 91 (n = 51), and 95 (n = 38). Presymptomatic CNS therapy consisted of intrathecal methotrexate (six doses) and cranial irradiation (18 Gy) in the IR AIEOP 87 study, and extended triple intrathecal therapy with methotrexate, cytarabine, and prednisone depending on age in the IR AIEOP-ALL 91 and 95 protocols (20 and 17 total doses, respectively). World Health Organization (WHO) grade 4 acute neurotoxicity criteria were employed. Patients with neurologic symptoms, in addition to physical examination, 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 out 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 intermediate risk protocols. The intensification of treatment, however, bettered event free survival (EFS) to 58%, 72% and 85% in IR AIEOP 87, 91 and 95 studies, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents / adverse effects
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / mortality
  • Central Nervous System Diseases / chemically induced*
  • Central Nervous System Diseases / epidemiology
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cytarabine / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Hydrocortisone / adverse effects
  • Incidence
  • Infant
  • Injections, Spinal
  • Italy / epidemiology
  • Male
  • Methotrexate / adverse effects*
  • Radiotherapy, Adjuvant
  • Retrospective Studies


  • Anti-Inflammatory Agents
  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Hydrocortisone
  • Methotrexate