TY - JOUR
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.
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology.
PY - 2017/8/1
Y1 - 2017/8/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85026725781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026725781&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.71.4774
DO - 10.1200/JCO.2016.71.4774
M3 - Article
C2 - 28535084
AN - SCOPUS:85026725781
SN - 0732-183X
VL - 35
SP - 2527
EP - 2534
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -