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

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
StatePublished - Aug 1 2017

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National Cancer Institute (U.S.)
Precursor Cell Lymphoblastic Leukemia-Lymphoma
B-Lymphocytes
Radiation Dosage
Recurrence
Central Nervous System Diseases
Residual Neoplasm
Therapeutics
Disease-Free Survival
Leukemia
Leukocytes
Survival Rate
Cell Count
Erythrocytes
Bone Marrow
Clinical Trials
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Journal of Clinical Oncology, Vol. 35, No. 22, 01.08.2017, p. 2527-2534.

Research output: Contribution to journalArticle

Winick, N, Devidas, M, Chen, S, Maloney, K, Larsen, E, Mattano, L, Borowitz, MJ, Carroll, A, Gastier-Foster, JM, Heerema, NA, Willman, C, Wood, B, Loh, ML, Raetz, E, Hunger, SP & Carroll, WL 2017, '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', Journal of Clinical Oncology, vol. 35, no. 22, pp. 2527-2534. https://doi.org/10.1200/JCO.2016.71.4774
Winick, Naomi ; Devidas, Meenakshi ; Chen, Si ; Maloney, Kelly ; Larsen, Eric ; Mattano, Leonard ; Borowitz, Michael J ; Carroll, Andrew ; Gastier-Foster, Julie M. ; Heerema, Nyla A. ; Willman, Cheryl ; Wood, Brent ; Loh, Mignon L. ; Raetz, Elizabeth ; Hunger, Stephen P. ; Carroll, William L. / 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. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 22. pp. 2527-2534.
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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.",
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T1 - Impact of initial CSF findings on outcome among patients with National Cancer Institute standard- and high-risk B-cell acute lymphoblastic leukemia

T2 - A report from the Children’s Oncology Group

AU - Winick, Naomi

AU - Devidas, Meenakshi

AU - Chen, Si

AU - Maloney, Kelly

AU - Larsen, Eric

AU - Mattano, Leonard

AU - Borowitz, Michael J

AU - Carroll, Andrew

AU - Gastier-Foster, Julie M.

AU - Heerema, Nyla A.

AU - Willman, Cheryl

AU - Wood, Brent

AU - Loh, Mignon L.

AU - Raetz, Elizabeth

AU - Hunger, Stephen P.

AU - Carroll, William L.

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N2 - 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.

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