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

Authors

  • Tomaž Prelog M.D.
  • Simon Buček
  • Andreja Brožič
  • Jakob Peterlin
  • Marko Kavčič
  • Maša Omerzel
  • Boštjan Markelc
  • Tanja Jesenko
  • Veronika Kloboves Prevodnik

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 de-independent CD10, CD19, CD27, CD34 and CD58.

Conclusions

Our results 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.

Author Biographies

Tomaž Prelog, M.D.

Department of Haemato-Oncology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia

 

Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

Simon Buček

Department of Cytopathology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Andreja Brožič

Department of Cytopathology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Jakob Peterlin

Institute for Biostatistics and Medical Informatics, University of Ljubljana, Ljubljana, Slovenia

Marko Kavčič

Department of Haemato-Oncology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia

Maša Omerzel

Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Boštjan Markelc

Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Tanja Jesenko

Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

 

Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

Veronika Kloboves Prevodnik

Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

 

Department of Cytopathology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

 

Institute of Pathology, Faculty of Medicine University of Maribor, Maribor, Slovenia

Correspondence to: Veronika Kloboves Prevodnik, Institute of Pathology, Faculty of Medicine University of Maribor, Maribor, Slovenia

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Published

2024-02-15

How to Cite

Prelog, T., Buček, S., Brožič, A., Peterlin, J., Kavčič, M., Omerzel, M., … Kloboves Prevodnik, V. (2024). The influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukaemia. Radiology and Oncology, 58(1), 133–144. Retrieved from https://radioloncol.com/index.php/ro/article/view/4264

Issue

Section

Clinical oncology