B‐lineage antigens that are useful to substitute CD19 for minimal residual disease monitoring in B cell precursor acute lymphoblastic leukemia after CD19 targeting

Abstract

Background: The potential loss of CD19 during targeted treatment of B cell precursor acute lymphoblastic leukemia (BCP-ALL) can hamper flow cytometric minimal residual disease (MRD) monitoring. In the current study, we present expression data for antigens that are candidates for CD19 substitution: surface CD22, CD24, CD10, and intracellular (i) CD79a.Methods: Bone marrow samples from 519 consecutive children (below 18 y.o.) with primary BCP-ALL were studied with a focus on expression of CD19, CD10, CD22, CD24, and iCD79a. As these antigens are planned to be used as substitutions for CD19 for primary B cell gating, only total expression on the leukemic population (≥95% cells) was considered appropriate.Results: It was found that each of these antigens is totally expressed in nearly 90% of patients. For each single marker, a subgroup of patients without complete positivity presented with BCP-ALL harboring diverse cytogenetic and molecular genetic aberrations. Based on expression data, we have developed algorithm of simultaneous application of these antigens for initial B-lineage compartment gating, that is applicable for nearly all patients after CD19 targeting. Conclusion:We conclude that the addition of CD22, CD24, and iCD79a to the conventional antibody panel and their application together with CD10 allow for the identification of B-lineage compartment including residual tumor blasts, for MFC-MRD searching in virtually all patients with BCP-ALL after CD19-directed treatment.

Reliable Flow-Cytometric Approach for Minimal Residual Disease Monitoring in Patients with B-Cell Precursor Acute Lymphoblastic Leukemia after CD19-Targeted Therapy

“…Because of the high incidence of CD19 negativity, it was necessary to search for a possible substitution for CD19 as the primary B-lineage antigen with antigen(s) of similar diagnostic value. The initial expression of CD22, CD24, CD10 and intracellular (i) CD79a was tested in a large cohort of primary BCP-ALL pediatric patients ( n = 519) [ 20 ]. It was found that the tested antigens were expressed by nearly all tumor cells (more than 95% of positive cells in the leukemic population) in 88.9% (CD22), 83.7% (iCD79a), 88.2% (CD10) and 94.7% (CD24) of patients [ 20 ].…”

“…The initial expression of CD22, CD24, CD10 and intracellular (i) CD79a was tested in a large cohort of primary BCP-ALL pediatric patients ( n = 519) [ 20 ]. It was found that the tested antigens were expressed by nearly all tumor cells (more than 95% of positive cells in the leukemic population) in 88.9% (CD22), 83.7% (iCD79a), 88.2% (CD10) and 94.7% (CD24) of patients [ 20 ]. Moreover, at least one of the studied markers was expressed on nearly all blasts in more than 95% of patients, and there were no patients in whom none of these antigens were found.…”

Acute lymphoblastic leukemia with the t(17;19) translocation: hope has appeared! Multimodal immunotherapy in a 3-year-old child with refractory disease: a case report

“…Мониторинг минимальной остаточной болезни (МОБ) проводился методом многоцветной проточной цитометрии согласно стандарту группы «Москва-Берлин» [5] с модификациями, необходимыми для эффективного определения МОБ в условиях проведения CD19-направленной терапии [6,7]. Кинетика МОБ на всем протяжении терапии показана на рисунке 5.…”

Issue highlights—November 2022

“…Similarly upon daratumumab treatment the identification of malignant plasma cells is not feasible with anti-CD38 labeling. In this Issue of Clinical Cytometry (Mikhailova et al, 2022) Mikhailova and coworkers investigated the applicable B-lineage markers in case of minimal residual disease detection in children suffering from B-cell precursor acute lymphoblastic leukemia after CD19 targeting. The pan B-cell surface marker CD19 molecule can be targeted either with the bispecific antibody blinatumomab or with T-lymphocytes harboring a chimeric antigen receptor against CD19.…”