Is next-generation sequencing a useful tool for the risk stratification of patients with T-ALL?

During the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, the ALL Hub spoke with Loïc Vasseur, Hôpital Saint-Louis, Paris, FR. We asked, Is next-generation sequencing (NGS) a useful tool for the risk stratification of patients with T-ALL?

Vasseur first highlights the gene alterations that have been identified as prognostic factors in T-ALL; including NOTCH1 and FBXW7, which are associated with a good prognostic impact; or TP53, p10, and DNMT3A, which are associated with an adverse prognostic impact. Currently, there is no consensus on risk stratification in T-ALL.

Then, Vasseur reviews the existing data on the role of NGS in the prognostic stratification of patients with T-ALL. Recent work, presented during ASH, demonstrated that NGS can identify other important gene alterations to stratify patients at a higher risk of relapse. Given the complexity of identifying prognostic factors, response to treatment and biological markers can also be used to determine the type and intensification of chemotherapy regimens, such as asparaginase, and to provide indications for the use of allogeneic stem cell transplantation.

NGS is also crucial when deciding the subgroup of patients that may benefit from targeted therapies; for example, patients with alterations in PHF6 or epigenetic regulators could benefit from BCL-2 inhibitors.

He concludes by emphasizing the importance of NGS for risk stratification in first-line T-ALL treatment, particularly the early adaptation of chemotherapy prior to minimal residual disease results and to guide the use of targeted therapies.