Early recovery of circulating immature B cells in B‐lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection

Xiao, Wenbin; Salem, Dalia; McCoy, Catharine S.; Lee, Daniel; Shah, Nirali N.; Stetler‐Stevenson, Maryalice; Yuan, Constance

doi:10.1002/cyto.b.21591

Cited by 17 publications

(10 citation statements)

References 44 publications

(106 reference statements)

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“…Another potential pitfall is the unusual population of mature CD10-positive, CD19-positive, surface immunoglobulin-positive intermediate B-cells that has been reported in the peripheral blood with delayed B-cell regeneration following anti-CD19 CAR-T and possibly other therapies (72). For example, anti-CD20 monoclonal antibody therapy and anti-CD19 CAR-T therapy have both been associated with decreased staining of non-neoplastic B-cells for the respective targeted antigen, which might be mistaken for aberrant antigen expression by neoplastic cells.…”

Section: Role Of Flow Cytometry In Therapeutic Decisionmentioning

confidence: 99%

“…For example, anti-CD20 monoclonal antibody therapy and anti-CD19 CAR-T therapy have both been associated with decreased staining of non-neoplastic B-cells for the respective targeted antigen, which might be mistaken for aberrant antigen expression by neoplastic cells. Another potential pitfall is the unusual population of mature CD10-positive, CD19-positive, surface immunoglobulin-positive intermediate B-cells that has been reported in the peripheral blood with delayed B-cell regeneration following anti-CD19 CAR-T and possibly other therapies (72). Therefore, it is important to inquire about prior therapy when encountering unusual findings by flow cytometric immunophenotyping.…”

Section: Role Of Flow Cytometry In Therapeutic Decision Making For Mamentioning

confidence: 99%

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The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

Seegmiller

Hsi

Craig

2018

Cytometry Part B Clinical

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Flow cytometry (FC) has a well-established role in the diagnostic evaluation of mature B-cell neoplasms. Effective assessment for lineage associated antigens, aberrant antigen expression, and immunoglobulin light chain restriction requires a welldesigned, optimized, and controlled FC assay. However, it is important for hematopathologists to know when flow cytometry has a more limited role, and other modalities, such as immunohistochemistry, cytogenetic and molecular testing, are more important. This review will discuss the features of an optimal FC assay for the evaluation of mature B-cell neoplasms, and the current role of FC in the diagnosis and sub-classification, prognostic assessment, identification of therapeutic targets, and assessment for disease response to therapy.

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Section: Role Of Flow Cytometry In Therapeutic Decisionmentioning

confidence: 99%

Section: Role Of Flow Cytometry In Therapeutic Decision Making For Mamentioning

confidence: 99%

The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

Seegmiller

Hsi

Craig

2018

Cytometry Part B Clinical

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“…In some cases, the responses to an anti-CD19 CAR T-cells immunotherapy are not as good as expected, especially when B-cells lose their receptors expression ( 146 , 147 ). Therefore, the need to identify other suitable targets on B-cells emerged.…”

Section: Second-generation Car Constructs For Hematological Malignancmentioning

confidence: 95%

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

et al. 2018

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Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.

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“…Post CD19 CAR‐T cells, unexpected patterns of recovery may be seen. For instance, a predominance of CD19 negative progenitors may be seen at early intervals after therapy (discussed further below) (Cherian et al, 2018) and some groups have described an increase in circulating hematogones (Xiao et al, 2018). Leukemic blasts in relapsed B‐ALL post CD19 directed T cell engaging therapies may be CD19 negative or positive (Pillai et al, 2019).…”

Section: Impact Of Targeted Immunotherapy On Data Assessmentmentioning

confidence: 99%

Flow cytometric assessment for minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma in the era of immunotherapy

Chen

Gao

Roshal

et al. 2023

Cytometry Part B Clinical

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Minimal/measurable residual disease (MRD) is the most important independent prognostic factor for patients with B‐lymphoblastic leukemia (B‐LL). MRD post therapy has been incorporated into risk stratification and clinical management, resulting in substantially improved outcomes in pediatric and adult patients. Currently, MRD in B‐ALL is most commonly assessed by multiparametric flow cytometry and molecular (polymerase chain reaction or high‐throughput sequencing based) methods. The detection of MRD by flow cytometry in B‐ALL often begins with B cell antigen‐based gating strategies. Over the past several years, targeted immunotherapy directed against B cell markers has been introduced in patients with relapsed or refractory B‐ALL and has demonstrated encouraging results. However, targeted therapies have significant impact on the immunophenotype of leukemic blasts, in particular, downregulation or loss of targeted antigens on blasts and normal B cell precursors, posing challenges for MRD detection using standard gating strategies. Novel flow cytometric approaches, using alternative strategies for population identification, sometimes including alternative gating reagents, have been developed and implemented to monitor MRD in the setting of post targeted therapy.

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Early recovery of circulating immature B cells in B‐lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection

Cited by 17 publications

References 44 publications

The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

Flow cytometric assessment for minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma in the era of immunotherapy

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