How I use next-generation sequencing-MRD to plan approach and prevent relapse after HCT for children and adults with ALL.
Lori S MufflyEmily C LiangJ Gregory DolanMichael A PulsipherPublished in: Blood (2024)
Measurable residual disease (MRD) evaluation by multiparameter flow cytometry (MFC) or quantitative polymerase chain reaction methods is an established standard of care for assessing risk of relapse before or after hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL). Next-generation sequencing (NGS)-MRD has emerged as a highly effective approach that allows for the detection of lymphoblasts at a level of <1 in 106 nucleated cells, increasing sensitivity of ALL detection by 2 to 3 logs. Early studies have shown superior results compared with MFC and suggest that NGS-MRD may allow for the determination of patients in whom reduced toxicity transplant preparative approaches could be deployed without sacrificing outcomes. Many centers/study groups have implemented immune modulation approaches based on MRD measurements that have resulted in improved outcomes. Challenges remain with NGS-MRD, because it is not commercially available in many countries, and interpretation of results can be complex. Through patient case review, discussion of relevant studies, and detailed expert opinion, we share our approach to NGS-MRD testing before and after HCT in pediatric and adult ALL. Improved pre-HCT risk classification and post-HCT monitoring for relapse in bone marrow and less invasive peripheral blood monitoring by NGS-MRD may lead to alternative approaches to prevent relapse in patients undergoing this challenging procedure.
Keyphrases
- cell cycle arrest
- flow cytometry
- acute lymphoblastic leukemia
- bone marrow
- patients undergoing
- peripheral blood
- cell death
- free survival
- healthcare
- machine learning
- ejection fraction
- young adults
- mesenchymal stem cells
- oxidative stress
- induced apoptosis
- loop mediated isothermal amplification
- acute myeloid leukemia
- minimally invasive
- metabolic syndrome
- real time pcr
- patient reported outcomes
- dna methylation
- cell proliferation
- case report
- mass spectrometry
- patient reported
- cell free