Impact of initial CSF findings on outcome among patients with National Cancer Institute standard- and high-risk B-cell acute lymphoblastic leukemia: A report from the Children’s Oncology Group

Naomi Winick, Meenakshi Devidas, Si Chen, Kelly Maloney, Eric Larsen, Leonard Mattano, Michael J. Borowitz, Andrew Carroll, Julie M. Gastier-Foster, Nyla A. Heerema, Cheryl Willman, Brent Wood, Mignon L. Loh, Elizabeth Raetz, Stephen P. Hunger, William L. Carroll

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Purpose: To determine the prognostic significance of blasts, and of white and red blood cells, in CSF samples at diagnosis of acute lymphoblastic leukemia (ALL), a uniform CSF and risk group classification schema was incorporated into Children’s Oncology Group B-cell ALL (B-ALL) clinical trials. Methods: CSF status was designated as follows: CNS1, no blasts; CNS2a to 2c,, 5 WBCs/mL and blasts with/ without $ 10 RBCs/mL or $ 5 WBCs/mL plus blasts, with WBCs $ 5 times the number of RBCs; CNS3a to 3c, $ 5 WBCs/mL plus blasts with/without $ 10 RBCs/mL or clinical signs of CNS disease. CNS2 status did not affect therapy; patients with CNS3 status received two extra intrathecal treatments during induction and augmented postinduction therapy with 18 Gy of cranial radiation. Results: Among 8,379 evaluable patients enrolled from 2004 to 2010, 7,395 (88.3%) had CNS1 status; 857 (10.2%), CNS2; and 127 (1.5%), CNS3. The 5-year event-free and overall survival rates were, respectively, 85% and 92.7% for CNS1, 76% and 86.8% for CNS2, and 76% and 82.1% for CNS3 (P, .001). In multivariable analysis that included age, race/ethnicity, initial WBC, and day-29 minimal residual disease, 0.1%, CSF blast, regardless of cell count, was an independent adverse predictor of outcome for patients with standard- or high-risk disease according to National Cancer Institute criteria. The EFS difference reflected a significant difference in the incidence of CNS, not marrow, relapse in patients with CNS1 versus CNS2 and/or CNS3 status. Conclusion: Low levels of CNS leukemia, regardless of RBCs, predict inferior outcome and higher rates of CNS relapse. These data suggest that additional augmentation of CNS-directed therapy is warranted for CNS2 disease.

Original languageEnglish (US)
Pages (from-to)2527-2534
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number22
DOIs
Publication statusPublished - Aug 1 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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