CD19-targeting immunotherapies including blinatumomab, a (CD19/CD3) bispecific T-cell engaging antibody, and CD19-chimeric antigen receptor (CAR) T cells have been highly effective for B-cell acute lymphoblastic leukemia (ALL)[1, 2]. However, up to 50% of B-cell ALL patients relapse after CD19-targeted therapies, the majority with CD19-negative disease [3–5]. Given increasing utilization of these newly FDA-approved therapies in standard treatment paradigms, serial evaluations of CD19 surface expression following these therapies will be necessary to monitor for changes in leukemic phenotype. As a referral center for therapies targeting CD22, an alternate B-cell antigen, we have a unique population of children and young adults with relapse or refractory disease to CD19 targeting [6–8]. Utilizing this cohort, we retrospectively analyzed serial CD19 surface expression to evaluate for dynamic changes in surface expression following immunotherapy.