How I Investigate Measurable Residual Disease in B-Cell Precursor Acute Lymphoblastic Leukemia After Therapy With Bi-Specific Monoclonal Antibodies and 19CAR-T Cells.

INTRODUCTION: Measurable residual disease (MRD) in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) following anti-CD19 targeted therapies requires specific strategies to identify residual blast cells due to loss or reduced CD19 expression that makes it inconsistent as a primitive marker for B-cell gating.

OBJECTIVE: Due to the increased access of BCP-ALL patients to therapies with CD3/CD19 bispecific T-cell engagers (BiTe) and CD19-targeted chimeric antigen receptor T-Cell (CAR-T), it is essential that flow cytometry laboratories are prepared to evaluate therapeutic responses.

MATERIAL AND METHODS: Here, validated strategies for MRD detection in the context of anti-CD19 therapies are described, accessible to flow cytometry laboratories according to their different facilities. The paper includes an 8-color flow cytometry (FC) strategy for BCP-ALL MRD based on alternative gating without the use of additional markers (Euroflow protocol), as well as other strategies using alternative markers to CD19, comprising 2 protocols using 8 colors, one using 10 colors and another 14 colors/15 markers.

CONCLUSION: Different strategies are needed to detect MRD without using CD19 for B-cell population gating after CD19-targeted therapies. However, it is essential that validated protocols are used according to the available resources to ensure reliable results for clinical decision-making.