Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia

Deborah A. Thomas, Susan O'Brien, Jeffrey L. Jorgensen, Jorge Cortes, Stefan Faderl, Guillermo Garcia-Manero, Srdan Verstovsek, Charles Koller, Sherry Pierce, Yang Huh, William Wierda, Michael J. Keating, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

Immunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20% was associated with lower 3-year rates of complete remission duration (CRD; 20% vs 55%, P < .001) and overall survival (OS; 27% vs 40%, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58% vs 42%, p = .04) and OS (60% vs 28%, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68% and 85%, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27% or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 x 10 9/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.

Original languageEnglish (US)
Pages (from-to)6330-6337
Number of pages8
JournalBlood
Volume113
Issue number25
DOIs
StatePublished - Nov 19 2009
Externally publishedYes

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Chemotherapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chromosomes
Monoclonal Antibodies
Drug Therapy
Philadelphia Chromosome
Group Psychotherapy
Leukocyte Count
Disease-Free Survival
Multivariate Analysis
Age Groups
Survival
Rituximab

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Thomas, D. A., O'Brien, S., Jorgensen, J. L., Cortes, J., Faderl, S., Garcia-Manero, G., ... Kantarjian, H. M. (2009). Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood, 113(25), 6330-6337. https://doi.org/10.1182/blood-2008-04-151860

Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. / Thomas, Deborah A.; O'Brien, Susan; Jorgensen, Jeffrey L.; Cortes, Jorge; Faderl, Stefan; Garcia-Manero, Guillermo; Verstovsek, Srdan; Koller, Charles; Pierce, Sherry; Huh, Yang; Wierda, William; Keating, Michael J.; Kantarjian, Hagop M.

In: Blood, Vol. 113, No. 25, 19.11.2009, p. 6330-6337.

Research output: Contribution to journalArticle

Thomas, DA, O'Brien, S, Jorgensen, JL, Cortes, J, Faderl, S, Garcia-Manero, G, Verstovsek, S, Koller, C, Pierce, S, Huh, Y, Wierda, W, Keating, MJ & Kantarjian, HM 2009, 'Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia', Blood, vol. 113, no. 25, pp. 6330-6337. https://doi.org/10.1182/blood-2008-04-151860
Thomas, Deborah A. ; O'Brien, Susan ; Jorgensen, Jeffrey L. ; Cortes, Jorge ; Faderl, Stefan ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Koller, Charles ; Pierce, Sherry ; Huh, Yang ; Wierda, William ; Keating, Michael J. ; Kantarjian, Hagop M. / Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. In: Blood. 2009 ; Vol. 113, No. 25. pp. 6330-6337.
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title = "Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia",
abstract = "Immunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20{\%} was associated with lower 3-year rates of complete remission duration (CRD; 20{\%} vs 55{\%}, P < .001) and overall survival (OS; 27{\%} vs 40{\%}, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58{\%} vs 42{\%}, p = .04) and OS (60{\%} vs 28{\%}, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68{\%} and 85{\%}, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27{\%} or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 x 10 9/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.",
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AU - Faderl, Stefan

AU - Garcia-Manero, Guillermo

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AU - Koller, Charles

AU - Pierce, Sherry

AU - Huh, Yang

AU - Wierda, William

AU - Keating, Michael J.

AU - Kantarjian, Hagop M.

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N2 - Immunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20% was associated with lower 3-year rates of complete remission duration (CRD; 20% vs 55%, P < .001) and overall survival (OS; 27% vs 40%, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58% vs 42%, p = .04) and OS (60% vs 28%, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68% and 85%, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27% or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 x 10 9/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.

AB - Immunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20% was associated with lower 3-year rates of complete remission duration (CRD; 20% vs 55%, P < .001) and overall survival (OS; 27% vs 40%, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58% vs 42%, p = .04) and OS (60% vs 28%, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68% and 85%, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27% or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 x 10 9/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.

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