Use of High-Throughput Sequencing of the Immunoglobulin Loci for Refined Risk Stratification in Pediatric B-ALL
Abstract
The scientific objective of this proposal is to improve outcomes for children with B-lymphoblastic leukemia (B-ALL) by finding a better way to predict which patients are likely to relapse (have their leukemia come back) after finishing their treatment and those who are likely to stay cancer-free over time. B-ALL is the most common childhood cancer. Thus, this work addresses the Fiscal Year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas of pediatric, adolescent, and young adult cancers and blood cancers. While outcomes are overall favorable, B-ALL still accounts for more childhood cancer deaths than most other cancers. In the proposed study we will investigate how we can use a new technology called immunoglobulin high throughput sequencing (Ig HTS) to improve the way we predict the risk of relapse in children with B-ALL. We will study ways we can use Ig HTS to more accurately identify patients who are at high risk for relapse so that we can change their cancer treatments accordingly and, hopefully, prevent their cancer from coming back. On the other hand, there are likely patients being treated with more intense chemotherapy than is needed for cure. We also will study ways that Ig HTS can help identify these patients so that we can give less intense treatment for their cancer, reducing short- and long-term treatment related side effects. The proposed research may fill gaps in cancer research that may affect mission readiness, both in terms of prognosis and treatment of B-ALL, and in terms of quality of life and survivorship, improving overall health and well-being of military families (FY22 PRCRP Military Health Focus Areas Gaps). Precisely tailoring therapy based on relapse risk will reduce relapses, deaths, and short- and long-term toxicities of therapy, aligned with the FY22 PRCRP Overarching Challenges of identifying strategies to predict treatment resistance and recurrence, developing strategies to reduce treatment effects, and elucidating mechanisms behind cancer epigenetics/genetics and cancer development to improve treatment methods. To answer these important questions, the proposed work will take advantage of an already ongoing clinical trial with lots of patient samples and data. The design of this translational study therefore minimizes duplication, enabling us to efficiently create a new algorithm incorporating Ig HTS that could have an immediate impact on the treatment of childhood B-ALL. Indeed, given that the Ig HTS is a clinical test, readily available to patients everywhere, our findings can be immediately added into the routine care of children with B-ALL. Overall, our findings will translate into the routine use of Ig HTS on patients with B-ALL. This will help minimize both the risk of cancer relapse as well as time in hospital for treatment due to tailored chemotherapeutic regimens. These outcomes would decrease the risk of active-duty Service Members being called home and enable early return to duty, while improving the overall health of our military Families and mission readiness.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310992
Entities
People
- Rachel Rau
Organizations
- United States Army