Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia

a report from the Childrens Cancer Study Group

D. R. Miller, Peter Felix Coccia, W. A. Bleyer, J. N. Lukens, S. E. Siegel, H. N. Sather, G. D. Hammond

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Abstract

The Childrens Cancer Study Group (CCSG) CCG-160 protocol series was designed to evaluate prognostic factors in acute lymphoblastic leukemia (ALL). Patients were assigned to one of three prognostic groups based upon initial WBC count and age. To determine the optimal duration of therapy, CCG-160 patients completing 2 years of treatment in continuous remission were randomized ('late randomization') to discontinue therapy or receive another year of maintenance therapy. The prognostic significance of early response to induction therapy, as measured by the percentage of lymphoblasts in the day-14 bone marrow (d14 BM) aspirate, was evaluated in 2,516 children. For 1,490 patients with complete data, the status of the d14 BM was a highly significant predictor of disease-free survival (DFS) by univariate and multivariate analysis (P < .0001). The observed/expected (O/E) failure rate in patients with d14 M1 (> 5% blasts), M2 (4% to 25% blasts), or M3 (< 25% blasts) BM rating who were subsequently M1 on day 28 or day 42, was .87, 1.59, and 2.30, respectively (P < .0001). Patients with M2 or M3 d14 BM were more likely to have L2 ALL (modified French-American-British [FAB] morphologic classification), P < .001). The significance of the d14 BM rating persisted after correction was made for WBC count and clinical prognostic groups using current CCSG criteria, except in infants less than 12 months of age. The d14 BM was also the most significant predictor of DFS in 975 patients after late randomization at 2 years following diagnosis. The O/E failure rate in patients with d14 M1, M2, or M3 BM was .88, 1.78, and 2.02, respectively (P = .0002, trend). Other significant predictors of late relapse were prognostic groups (P = .0003, trend) and initial WBC count (P = .004, trend). Predictive for both early and late relapse of ALL, early response should be monitored closely and alternative treatment regimens should be considered for slow responders.

Original languageEnglish (US)
Pages (from-to)1807-1815
Number of pages9
JournalJournal of Clinical Oncology
Volume7
Issue number12
DOIs
StatePublished - Jan 1 1989

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Recurrence
Bone Marrow
Neoplasms
Random Allocation
Therapeutics
Survival Analysis
Multivariate Analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia : a report from the Childrens Cancer Study Group. / Miller, D. R.; Coccia, Peter Felix; Bleyer, W. A.; Lukens, J. N.; Siegel, S. E.; Sather, H. N.; Hammond, G. D.

In: Journal of Clinical Oncology, Vol. 7, No. 12, 01.01.1989, p. 1807-1815.

Research output: Contribution to journalArticle

Miller, D. R. ; Coccia, Peter Felix ; Bleyer, W. A. ; Lukens, J. N. ; Siegel, S. E. ; Sather, H. N. ; Hammond, G. D. / Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia : a report from the Childrens Cancer Study Group. In: Journal of Clinical Oncology. 1989 ; Vol. 7, No. 12. pp. 1807-1815.
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abstract = "The Childrens Cancer Study Group (CCSG) CCG-160 protocol series was designed to evaluate prognostic factors in acute lymphoblastic leukemia (ALL). Patients were assigned to one of three prognostic groups based upon initial WBC count and age. To determine the optimal duration of therapy, CCG-160 patients completing 2 years of treatment in continuous remission were randomized ('late randomization') to discontinue therapy or receive another year of maintenance therapy. The prognostic significance of early response to induction therapy, as measured by the percentage of lymphoblasts in the day-14 bone marrow (d14 BM) aspirate, was evaluated in 2,516 children. For 1,490 patients with complete data, the status of the d14 BM was a highly significant predictor of disease-free survival (DFS) by univariate and multivariate analysis (P < .0001). The observed/expected (O/E) failure rate in patients with d14 M1 (> 5{\%} blasts), M2 (4{\%} to 25{\%} blasts), or M3 (< 25{\%} blasts) BM rating who were subsequently M1 on day 28 or day 42, was .87, 1.59, and 2.30, respectively (P < .0001). Patients with M2 or M3 d14 BM were more likely to have L2 ALL (modified French-American-British [FAB] morphologic classification), P < .001). The significance of the d14 BM rating persisted after correction was made for WBC count and clinical prognostic groups using current CCSG criteria, except in infants less than 12 months of age. The d14 BM was also the most significant predictor of DFS in 975 patients after late randomization at 2 years following diagnosis. The O/E failure rate in patients with d14 M1, M2, or M3 BM was .88, 1.78, and 2.02, respectively (P = .0002, trend). Other significant predictors of late relapse were prognostic groups (P = .0003, trend) and initial WBC count (P = .004, trend). Predictive for both early and late relapse of ALL, early response should be monitored closely and alternative treatment regimens should be considered for slow responders.",
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