Strong expansion of normal CD19‐negative B‐cell precursors after the use of blinatumomab in the first‐line therapy of acute lymphoblastic leukaemia in children.

Serial evaluation of CD19 surface expression in pediatric B-cell malignancies following CD19-targeted therapy. In contrast to the CD19-negative precursors, the level of CD19-positives increased significantly during the first three months of maintenance therapy, although the continued presence of B-lineage regeneration remained more or less stable (Fig. Keywords: CD19 targeting; minimal residual disease; ALL; flow cytometry; CD19-negative precursors EN CD19 targeting minimal residual disease ALL flow cytometry CD19-negative precursors e6 e9 4 12/27/21 20220101 NES 220101 Targeting the pan-B-lymphocyte antigen CD19 with the bispecific T-cell engager blinatumomab is one of the modern ways of treating acute lymphocytic B-cell precursor leukaemia (BCP-ALL).1,2 This drug has been very successful in treating patients with relapsed/refractory (R/R) disease,3,4 but it has recently been shown that blinatumomab is also effective in eradicating minimal residual disease (MRD) in patients with relapsed or primary BCP-ALL.5,6 Loss of the target molecule is one of the key mechanisms for leukaemia cells to escape the selective pressure of blinatumomab.7,8 The resulting possible CD19 negativity interferes with MRD monitoring by multicolour flow cytometry (MFC), which is usually based on analysis of the CD19-positive compartment.9 On the other hand, the use of other early B-line antigens [CD22, CD24, CD10, intracellular (i) CD79a] instead of CD19 for primary B-cell gating, such as to improve the MFC-MRD technique in the case of CD19-targeted treatment,7,10,11 could lead to errors in the interpretation of the immunophenotype of normal haematopoietic cells. CD19-negative B-cell precursors were gated as described previously.12 All BM samples obtained after completion of blinatumomab were MFC-MRD-negative, including those from patients who were MFC-MRD-positive at EOI ( I n i = 7, median MFC-MRD 0-030%, range 0-001-0-166%). [Extracted from the article]