<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>Flow cytometry plays is important in the diagnosis of acute lymphoblastic leukaemia (ALL) and when antigen-specific immunotherapy is indicated. We have investigated the effects of prednisolone, vincristine, daunorubicin, asparaginase and methotrexate on the antigen expression on blast cells that could influence the planning of antigen-specific therapy as well as risk-based treatment assignment.</p>
</sec>
<sec><h3>Patients and methods</h3>
<p>Patients aged ≤ 17 years with <italic>de novo</italic> B-cell ALL (B-ALL) were enrolled in the study. Blast cells were isolated and exposed <italic>in vitro</italic> to 5 individual cytotoxic drugs in logarithmically increasing concentrations. Then, the expression of CD10, CD19, CD20, CD27, CD34, CD45, CD58, CD66c and CD137 antigens was determined by quantitative flow cytometry.</p>
</sec>
<sec><h3>Results</h3>
<p>Cytotoxic drugs caused dose-dependent or dose-independent modulation of antigen expression. Daunorubicin caused a dose-dependent down-modulation of CD10, CD19, CD34, CD45 and CD58 and an up-modulation of CD137. Vincristine caused a dose-dependent down-modulation of CD19 and CD58 and an up-modulation of CD45. Daunorubicin also caused dose-independent down-modulation of CD27 and prednisolone down-modulation of CD10, CD19, CD27, CD34 and CD58. Down-modulation of CD20 was detected only in relation to the specific dose of daunorubicin.</p>
</sec>
<sec><h3>Conclusions</h3>
<p>The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.</p>
</sec>
</abstract>

Background
Flow cytometry plays is important in the diagnosis of acute lymphoblastic leukaemia (ALL) and when antigen-specific immunotherapy is indicated. We have investigated the effects of prednisolone, vincristine, daunorubicin, asparaginase and methotrexate on the antigen expression on blast cells that could influence the planning of antigen-specific therapy as well as risk-based treatment assignment.

Patients and methods
Patients aged ≤ 17 years with de novo B-cell ALL (B-ALL) were enrolled in the study. Blast cells were isolated and exposed in vitro to 5 individual cytotoxic drugs in logarithmically increasing concentrations. Then, the expression of CD10, CD19, CD20, CD27, CD34, CD45, CD58, CD66c and CD137 antigens was determined by quantitative flow cytometry.

Results
Cytotoxic drugs caused dose-dependent or dose-independent modulation of antigen expression. Daunorubicin caused a dose-dependent down-modulation of CD10, CD19, CD34, CD45 and CD58 and an up-modulation of CD137. Vincristine caused a dose-dependent down-modulation of CD19 and CD58 and an up-modulation of CD45. Daunorubicin also caused dose-independent down-modulation of CD27 and prednisolone down-modulation of CD10, CD19, CD27, CD34 and CD58. Down-modulation of CD20 was detected only in relation to the specific dose of daunorubicin.

Conclusions
The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.

The influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukaemia

Department of Haemato-Oncology, University Children’s Hospital

Institute for Biostatistics and Medical Informatics

Institute of Pathology, Faculty of Medicine

Radiology and Oncology

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
Flow cytometry plays is important in the diagnosis of acute lymphoblastic leukaemia (ALL) and when antigen-specific immunotherapy is indicated. We...

The influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukaemia

Article Category: Research Article

Pubblicato online: 21 feb 2024

Pagine: 133 - 144

Ricevuto: 14 mag 2023

Accettato: 06 dic 2023

DOI: https://doi.org/10.2478/raon-2024-0006

Parole chiave
immunophenotypic changes, chemotherapy, immunotherapy, paediatric B-ALL

© 2024 Tomaz Prelog et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

The influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukaemia

Article Category: Research Article

Pubblicato online: 21 feb 2024

Pagine: 133 - 144

Ricevuto: 14 mag 2023

Accettato: 06 dic 2023

DOI: https://doi.org/10.2478/raon-2024-0006

Parole chiaveimmunophenotypic changes, chemotherapy, immunotherapy, paediatric B-ALL

© 2024 Tomaz Prelog et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Parole chiave
immunophenotypic changes, chemotherapy, immunotherapy, paediatric B-ALL