The Significance of CD20 Intensity Variance in Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Abstract

B-cell precursor acute lyphoblastic leukemia (ALL) is a common pediatric malignancy and patients may have significant benefits from monoclonal antibodies therapy with increased survival rates. Positive CD20 expression is identified in about half of these patients and its presence may serve as a prognostic factor in disease evolution. We performed a retrospective study including 114 patients diagnosed with B-ALL and evaluated the expression of CD20 through flow cytometry at diagnosis and on day 15. Additional immunophenotypic analyses as well as cytogenetic and molecular genetic analyses were also performed. We observed an increase in the mean fluorescence intensity (MFI) of CD20 between diagnosis-1.9 (1.2-3.26) and day 15: 6.17 (2.14-27.4), (p < 0.0001). Furthermore, we assessed that both diagnosis and day 15 CD20 MFI had an impact on RFS and OS, respectively, for cut-off values of >8.08 at diagnosis and >28.65 at day 15. In conclusion, CD20 expression appears to be a poor prognostic feature of B-ALL in pediatric patients. In this study, stratification of the outcome by the intensity of CD20 has implications concerning the allocation to rituximab-based chemotherapy and may offer new, potentially useful information for pediatric patients with B-ALL.

Keywords: B-cell precursor acute lymphoblastic leukemia; CD20; flow cytometry; immunophenotyping; pediatric patients; survival analysis.

Figure 1

The difference in CD20 MFI between diagnosis and day 15. Centrality and dispersion measures were represented in the form of box and whiskers.

Figure 2

MFI CD20 diagnosis, day 15 and delta CD20 impact on RFS. (A,B) Survival was represented in the form of Kaplan-Meier plots and an accompanying table showing the number of patients at risk.

Figure 3

“Sliding window” approach on determining the succession of cut-off points that are significantly associated with RFS and OS. Each possible cut-off point was assessed and their respective log10 HR (95% CI) were plotted.