Therapy assessment of pediatric chronic myeloid leukemia (CML) using combined analyses of RNA/DNA response dynamics

Background Optimal treatment of pediatric CML requires a patient specific risk stratification and the comparability of individual therapy responses. A deeper understanding of the CML cells eradication dynamic is needed to make earlier therapy decisions. Methods: Besides transcript-based monitoring, DNA-based quantification was performed using the droplet digital PCR (ddPCR). A total of 1348 specimens from 65 pediatric CML patients were included. Therapy response models were designed separately for RNA-/DNA-monitoring. Data was evaluated using moving quantiles analyses. Results: Combined analyses show a stronger reduction of BCR-ABL1 transcripts compared to BCR-ABL1 copy numbers in the first three months of therapy. These data suggest that the initial reduction of CML cells is lower than the transcript-monitoring indicates. By applying moving quantiles analyses, patient specific therapy responses can be assigned to risk groups. Conclusion: RNA/DNA response models and moving quantiles analyses represent advanced diagnostic techniques to detect poor responders earlier. Prospectively, combined RNA-/DNA quantification may be used to assess the practicability of therapy stop trials.

Publication History

Article published online:
13 May 2020