An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia

J Clin Oncol. 1995 Feb;13(2):333-8. doi: 10.1200/JCO.1995.13.2.333.


Purpose: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL).

Patients and methods: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered.

Results: All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean +/- SE) was 70% +/- 11%. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission.

Conclusion: This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Central Nervous System / radiation effects
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / radiotherapy
  • Central Nervous System Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Combined Modality Therapy
  • Critical Care
  • Female
  • Humans
  • Infant
  • Injections, Intravenous
  • Injections, Spinal
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / radiotherapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Radiotherapy Dosage
  • Recurrence
  • Remission Induction
  • Time Factors


  • Methotrexate