Treatment of CNS relapse in children with acute lymphoblastic leukemia: A Pediatric Oncology Group study

Noomi J. Winick, Stephen D. Smith, Jonathan Shuster, Stephen Lauer, Moody D. Wharam, Vita Land, George Buchanan, Gaston Rivera

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Purpose: To assess the efficacy and toxicity of chemotherapy and cranial radiation for the treatment of children with acute lymphoblastic leukemia (ALL) following first isolated CNS relapse. Patients and Methods: One hundred twenty children were treated on Pediatric Oncology Group (POG) protocol 8304. All children had received prophylactic CNS therapy during their initial treatment. The treatment protocol included a four-drug reinduction and six weekly doses of triple intrathecal therapy (TIT). Cranial radiation, 24 Gy, was followed by monthly TIT. Systemic consolidation and maintenance therapy included 6-week cycles of mercaptopurine/methotrexate (6MP/MTX) and vincristine/cyclophosphamide (VCR/CTX), with randomization to intervening pulses of prednisone/doxorubicin (PDN/DOX) or teniposide (VM26)/cytarabine (Ara-C) for a total of 88 weeks. Results: All 120 patients achieved a second complete remission. There have been 61 protocol failures. Thirty-five patients had a bone marrow relapse, four with simultaneous CNS involvement and one with concurrent testicular leukemia. Thirteen patients had a second isolated CNS relapse, 10 a testicular relapse, and two relapsed in other sites. One patient died in remission. Overall event-free survival (EPS) at 4 years was 46% ± 7%. The toxicity associated with this protocol was minimal except for leukoencephalopathy, which occurred in 20 (17%) patients. The treatment comparison between VM26/Ara-C or PDN/DOX pulses showed a trend toward superior EPS (P = .12) in favor of VM-26/Ara-C. Conclusion: To date, this represents the largest series of patients with ALL treated uniformly for an isolated CNS relapse. Since marrow relapse remains the primary site of failure, future protocols must intensify systemic therapy.

Original languageEnglish (US)
Pages (from-to)271-278
Number of pages8
JournalJournal of Clinical Oncology
Issue number2
StatePublished - 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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