ALL-5: Exploring the prognostic significance of minimal residual disease (MRD) in children with ALL

Challenge:

Quantification of minimal residual disease (MRD) is a cornerstone of treatment response assessment and risk stratification in acute lymphoblastic leukemia (ALL), and the prognostic impact of MRD at different time points has been investigated across many therapeutic protocols. However, at present, there remains a lack of established prognostic biomarkers for risk stratification, especially in T-ALL, which reflect the underlying disease burden. Additionally, apart from absolute MRD values, the combined evaluation of MRD, and the analysis of log reduction rates between different time points, reflecting the different blast clearance kinetics and possibly different underlying biology, is still an issue that has not been addressed and fully evaluated. In this frame, there are few data on evaluated blast clearance kinetics between the time-points of day 15 and end of induction (EOI) therapy, as well between the time points of end of induction (EOI) and end of consolidation (EOC).

Previous results suggest that MRD quantifications, log-reduction rates and blast clearance kinetics impact survival and relapse outcomes significantly. This study aims to determine whether the combination of MRD values, and evaluation of the leukemia burden decrease by log-reduction rates, may provide a new tool for predicting relapse and patient outcomes in both B-cell and T-cell ALL.

Project Partnership

Aghia Sophia” Children’s Hospital, Athens, Greece

Project Leadership

Mirella Ampatzidou, Aghia Sophia” Children’s Hospital, Athens, Greece

Sophia Polychronopouloun, Aghia Sophia” Children’s Hospital, Athens, Greece

Impact

The combination of MRD values and leukemia burden decrease by MRD log-reduction rates may serve as useful tools in the prediction of relapse and patient outcomes in both B-cell ALL and T-cell ALL subgroups.
This MRD-based model may serve as a new surrogate marker for modern ALL risk stratification, which could be incorporated into present treatment protocols, identifying a subgroup of patients at either a higher or lower relapse risk.

Project Summary

There has been no evaluation of the combination of MRD, log-reduction rates between different time points, the different blast clearance kinetics and possible underlying copy number aberrations (CNAs). Therefore, this research aims to describe the prognostic significance of MRD log reduction in pediatric ALL patients at different time points during induction and consolidation therapy using data from the HARMONY database.

This retrospective analysis will utilize data from both B-cell and T-cell ALL pediatric patients which has been obtained by flow cytometry (FC) or polymerase chain reaction (PCR) measurement of MRD. MRD data from approximately 1000 ALL patients will be analyzed, with a sole focus on patients <18 years old. Data will be analyzed using numerous approaches, including the evaluation of key survival endpoints and specific patient subgroups.

The overall aims of this study are as follows:

To understand treatment-response assessment via quantification of MRD at combined different treatment time points in children with ALL.
To evaluate the prognostic impact of absolute MRD values at different treatment time points.
To understand the combined evaluation of MRD and MRD log-reduction rates between different time points, as well as the correlation with survival rates and relapse prediction.
To validate the MRD log reduction model in pediatric ALL patients

Public-private partnership for Big Data in Hematology

HARMONY and HARMONY PLUS are funded through the Innovative Medicines Initiative (IMI), Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. Funding is received from the IMI 2 Joint Undertaking and is listed under grant agreement for HARMONY No. 116026 and grant agreement for HARMONY PLUS No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA).