KEY TAKEAWAYS
- The study aimed to investigate the impact of cytotoxic drugs on blast cell antigen expression in pediatric B precursor ALL patients.
- Researchers noticed significant antigen modulation by cytotoxic drugs, emphasizing caution in their use before bispecific antibodies in pediatric B precursor ALL patients.
Flow cytometry is pivotal in diagnosing acute lymphoblastic leukemia (ALL) and guiding antigen-specific immunotherapy.
Tomaz Prelog and the team aimed to investigate the effects of prednisolone, vincristine, daunorubicin, asparaginase, and methotrexate impact blast cell antigen expression, influencing therapy planning and risk-based treatment assignment.
They performed an inclusive analysis involving patients aged ≤17 years with de novo B-cell ALL (B-ALL). Blast cells were isolated and exposed in vitro to five individual cytotoxic drugs at logarithmically increasing concentrations. Subsequently, the quantitative flow cytometry method was employed to determine the expression levels of CD10, CD19, CD20, CD27, CD34, CD45, CD58, CD66c, and CD137 antigens.
In the cytotoxic drug effects, daunorubicin induced dose-dependent and dose-independent antigen modulation. In a dose-dependent, CD10, CD19, CD34, CD45, and CD58 exhibited down-modulation, while CD137 showed up-modulation. Vincristine led to a dose-dependent down-modulation of CD19 and CD58 and an up-modulation of CD45.
Additionally, daunorubicin caused dose-independent down-modulation of CD27, and prednisolone down-modulated CD10, CD19, CD27, CD34, and CD58. CD20 down-modulation was specifically linked to daunorubicin dosage.
The study concluded that cytotoxic drugs induce significant alterations in antigen expression crucial for immunotherapy. Importantly, daunorubicin, prednisolone, and vincristine led to down-modulation of CD19 and CD58, suggesting their potential avoidance in bridging therapy before bispecific antibodies or CAR-T cell therapy. Moreover, drug-induced immunophenotypic changes on blast cells may impact risk-based treatment assignment. No funding information was available.
Source: https://pubmed.ncbi.nlm.nih.gov/38378030/
Prelog T, Bucek S, Brozic A, et al. (2024). ‘’The influence of cytotoxic drugs on the immunophenotype of blast cells in paediatric B precursor acute lymphoblastic leukemia.’’ Radiol Oncol. 2024 Feb 21;58(1):133-144. doi: 10.2478/raon-2024-0006. PMID: 38378030; PMCID: PMC10878768.
