Immunophenotype of Measurable Residual Blast Cells as an Additional Prognostic Factor in Adults with B-Cell Acute Lymphoblastic Leukemia

Abstract

Measurable residual disease (MRD) is a well-known independent prognostic factor in acute leukemias, and multicolor flow cytometry (MFC) is widely used to detect MRD. MFC is able not only to enumerate MRD accurately but also to describe an antigen expression profile of residual blast cells. However, the relationship between MRD immunophenotype and patient survival probability has not yet been studied. We determined the prognostic impact of MRD immunophenotype in adults with B-cell acute lymphoblastic leukemia (B-ALL). In a multicenter study RALL-2016 (NCT03462095), 267 patients were enrolled from 2016 to 2022. MRD was assessed at the end of induction (day 70) in 94 patients with B-ALL by six- or 10-color flow cytometry in the bone marrow specimens. The 4 year relapse-free survival (RFS) was lower in MRD-positive B-ALL patients [37% vs. 78% (p < 0.0001)]. The absence of CD10, positive expression of CD38, and high expression of CD58 on MRD cells worsened the 4 year RFS [19% vs. 51% (p = 0.004), 0% vs. 51% (p < 0.0001), and 21% vs. 40% (p = 0.02), respectively]. The MRD immunophenotype is associated with RFS and could be an additional prognostic factor for B-ALL patients.

Keywords: acute lymphoblastic leukemia; flow cytometry; immunophenotype; measurable residual disease.

Figure 1

Description of CD10, CD34, CD38, CD20, and CD58 expression in residual blast cells (MRD—measurable residual disease).

Figure 2

Description of CD19 and CD45 expression in residual blast cells (MRD—measurable residual disease).

Figure 3

Relapse-free survival of patients with B-cell acute lymphoblastic leukemia depending on MRD at different timepoints: (a) at the end of induction II (day 70); (b) at the end of consolidation III (day 133); (c) at the end of consolidation V (day 190). The initial date was the date of the MRD assessment.

Figure 4

Analysis of immunophenotype of measurable residual blast cells detected at the end of induction: (a) Dendrogram and heat map of semiquantitative immunophenotype description (1: “−”; 2: “−/+”; 3: “dim”; 4: “+/−”; 5: “+”; 6: “high”); (b) relapse-free survival depending on belonging to the clusters highlighted on the dendrogram. The initial date was the end of induction.

Figure 5

Relapse-free survival of patients depending on expression of CD10 (a), CD38 (b), and CD58 (c) on measurable residual blast cells detected at the end of induction. The initial date was the end of induction.

Figure 6

Relapse-free survival of patients depending on expressions of CD10, CD38, and CD58 on measurable residual blast cells detected at the end of induction: (a) combination of CD10⁻ and CD38⁺ and CD58^high; (b) CD10⁻, CD38⁺, or CD58^high immunophenotype. The initial date was the end of induction.