Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: A pediatric oncology group study

W. Crist, J. Boyett, J. Jackson, T. Vietti, Michael J Borowitz, A. Chauvenet, N. Winick, A. Ragab, D. Mahoney, D. Head, R. Iyer, H. Wagner, J. Pullen

Research output: Contribution to journalArticle

Abstract

We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients ≥ 1 year and ≤ 21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2 every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96%. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (± SE) was 63% ± 2% (pre-B = 51% ± 5% and early pre-B = 66% ± 3%). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P = .0004); this association included both bone marrow and CNS remissions (P = .0004 and P = .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk-specific treatment protocols.

Original languageEnglish (US)
Pages (from-to)1252-1259
Number of pages8
JournalBlood
Volume74
Issue number4
StatePublished - 1989
Externally publishedYes

Fingerprint

Pediatrics
B-Lymphoid Precursor Cells
Oncology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cells
Chemotherapy
Ploidies
Clinical Protocols
Random Allocation
Karyotype
Methotrexate
Regression analysis
Disease-Free Survival
Bone
Randomized Controlled Trials
Bone Marrow
Regression Analysis
Clinical Trials
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia : A pediatric oncology group study. / Crist, W.; Boyett, J.; Jackson, J.; Vietti, T.; Borowitz, Michael J; Chauvenet, A.; Winick, N.; Ragab, A.; Mahoney, D.; Head, D.; Iyer, R.; Wagner, H.; Pullen, J.

In: Blood, Vol. 74, No. 4, 1989, p. 1252-1259.

Research output: Contribution to journalArticle

Crist, W, Boyett, J, Jackson, J, Vietti, T, Borowitz, MJ, Chauvenet, A, Winick, N, Ragab, A, Mahoney, D, Head, D, Iyer, R, Wagner, H & Pullen, J 1989, 'Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: A pediatric oncology group study', Blood, vol. 74, no. 4, pp. 1252-1259.
Crist, W. ; Boyett, J. ; Jackson, J. ; Vietti, T. ; Borowitz, Michael J ; Chauvenet, A. ; Winick, N. ; Ragab, A. ; Mahoney, D. ; Head, D. ; Iyer, R. ; Wagner, H. ; Pullen, J. / Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia : A pediatric oncology group study. In: Blood. 1989 ; Vol. 74, No. 4. pp. 1252-1259.
@article{19de3456e96d4b7fbd80f21f93d5c2f6,
title = "Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: A pediatric oncology group study",
abstract = "We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients ≥ 1 year and ≤ 21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2 every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96{\%}. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (± SE) was 63{\%} ± 2{\%} (pre-B = 51{\%} ± 5{\%} and early pre-B = 66{\%} ± 3{\%}). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P = .0004); this association included both bone marrow and CNS remissions (P = .0004 and P = .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk-specific treatment protocols.",
author = "W. Crist and J. Boyett and J. Jackson and T. Vietti and Borowitz, {Michael J} and A. Chauvenet and N. Winick and A. Ragab and D. Mahoney and D. Head and R. Iyer and H. Wagner and J. Pullen",
year = "1989",
language = "English (US)",
volume = "74",
pages = "1252--1259",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

TY - JOUR

T1 - Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia

T2 - A pediatric oncology group study

AU - Crist, W.

AU - Boyett, J.

AU - Jackson, J.

AU - Vietti, T.

AU - Borowitz, Michael J

AU - Chauvenet, A.

AU - Winick, N.

AU - Ragab, A.

AU - Mahoney, D.

AU - Head, D.

AU - Iyer, R.

AU - Wagner, H.

AU - Pullen, J.

PY - 1989

Y1 - 1989

N2 - We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients ≥ 1 year and ≤ 21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2 every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96%. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (± SE) was 63% ± 2% (pre-B = 51% ± 5% and early pre-B = 66% ± 3%). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P = .0004); this association included both bone marrow and CNS remissions (P = .0004 and P = .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk-specific treatment protocols.

AB - We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients ≥ 1 year and ≤ 21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2 every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96%. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (± SE) was 63% ± 2% (pre-B = 51% ± 5% and early pre-B = 66% ± 3%). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P = .0004); this association included both bone marrow and CNS remissions (P = .0004 and P = .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk-specific treatment protocols.

UR - http://www.scopus.com/inward/record.url?scp=0024421371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024421371&partnerID=8YFLogxK

M3 - Article

C2 - 2669998

AN - SCOPUS:0024421371

VL - 74

SP - 1252

EP - 1259

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -