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, 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

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.

Figures

Figure 1
Figure 1
Outcome by CD20 expression (positive or negative by traditional cut point of 20%) and by therapy. Survival (A) and CR duration (B) are depicted.
Figure 2
Figure 2
Outcome by CD20 expression and therapy according to age subgroups. Age 30 or less (A), age 31 to 59 (B), and age at least 60 (C) years.
Figure 3
Figure 3
Outcome by degree of CD20 expression. Survival (A) and CR duration (B) by quartiles of CD20 expression. CR duration (C) by centiles of CD20 expression.

Source: PubMed

3
Sottoscrivi