ASH Clinical News September 2015 | Page 67

FEATURE quencing amplifies all possible sequences in the gene region of interest. At diagnosis, patients get a signature for that particular leukemia that can be screened for in subsequent tests. “In standard PCR testing, we have to do a special test for each patient. In nextgeneration sequencing we only do one test for all possible sequences and then look for that particular signature,” Michael J. Borowitz, MD, PhD, professor of pathology and oncology at Johns Hopkins Medical Institutions in Baltimore, Maryland, explained. Next-generation sequencing has a greater sensitivity and, according to Dr. Hunger, is able to “get down to one cell of a 100,000 and, potentially, to one cell in a million.” This emerging technology is predicted to become the future of MRD detection for ALL, but there are still hurdles to overcome – including a need for large-scale clinical trials – before it is used widely in practice. Powerful Prognostics MRD monitoring aids in risk stratification, can be used to determine the efficacy of treatment, identify the presence of tumor cells after therapy, or determine the best timing for a stem cell transplantation. MRD may also forecast the possibility of a relapse – although those in the field caution that MRD does not define relapse. Ample research has shown that MRD is a valuable risk-prediction tool in pediatric patients with ALL. In a recent study, Dr. Pui and colleagues found that patients who had MRD on day 19 of remission induction therapy had significantly worse 10-year event-free survival (EFS) rates than those who tested negative – regardless of their initial risk stratification.1 Patients who were categorized as being low-risk but who had MRD levels ≥1 percent had 10-year EFS rates of just 69.2 percent, while patients who were initially categorized as standard-risk but who had MRD levels <1 percent had 10-year EFS rates of 82.9 percent. Due to its highly prognostic nature, hematologists and oncologists often use MRD monitoring to tailor therapies for pediatric patients based on their risk level. For instance, Dr. Borowitz explained, patients who test positive for MRD or those who have the highest levels of ɕͥ