CD19-negative relapse in B-cell precursor acute lymphoblastic leukemia (ALL) is observed as an infrequent event after chemotherapy and in up to 20% of patients after CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy. Patients with CD19-negative relapse usually have a poor prognosis.
The mechanisms underlying CD19-negative relapse are not fully understood but are important to elucidate to further optimize CD19-directed immunotherapies. Monitoring blasts in patients with CD19-negative relapse by flow cytometry is challenging due to the lack of cell surface markers other than CD19 that are consistently expressed.
Furthermore, CD19 is often used as a parameter to quantify minimal residual disease (MRD) and diagnose relapse. Potential markers to monitor persistent or recurrent leukemic blasts in an emergent CD19-negative blast population include B-cell lineage antigens (CD20, CD22, CD24, and intracellular [i]CD79a) and the common ALL antigen CD10.