Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia in Adolescents and Young Adults

Amy Y. Wang, MD, MPH; Lori S. Muffly, MD, MS; Wendy Stock, MD


J Oncol Pract. 2020;16(5):231-238. 

In This Article

Clinical Significance of Minimal Residual Disease

Long championed by pediatric ALL physicians and investigators, measurement of MRD has now become a standard of care in ALL across the age spectrum. Although studies vary in terms of patient age group, MRD methodology, and time point of MRD measurement (with postinduction, postconsolidation, and peri-transplantation being the most commonly reported), a comprehensive meta-analysis recently demonstrated that MRD detection in ALL retains independent prognostic value across ALL settings.[29] Measurement of MRD after completion of induction therapy aids in identifying AYAs without residual disease who on average will have excellent outcomes after pediatric therapeutic regimens. For example, among the patients who underwent study-specific MRD testing by allele-specific oligonucleotide polymerase chain reaction in CALGB 10403, the disease-free survival (DFS) for those achieving MRD negativity after induction was significantly superior (3-year DFS, 85%; 95% CI, 74% to 98%) relative to patients with detectable MRD at greater than 10−4 (3-year DFS, 54%; 95% CI, 41% to 71%).[21] Unpublished 3-year OS data were 91% (95% CI, 81% to 100%) versus 70% (95% CI, 57% to 85%; P = .02), respectively (personal communication with W. Stock, June 2019).

The clinical utility of MRD measurement is not limited to only prognostication; MRD has now become an intervenable clinical end point. For example, blinatumomab, the bispecific monoclonal T-cell engager antibody that binds both CD3 and CD19, is US Food and Drug Administration (FDA) approved for the treatment of MRD-positive disease, and a number of clinical trials either accept MRD in the absence of morphological disease as an inclusion criterion or use MRD as a trial end point. A variety of methodologies exist for monitoring MRD, including flow cytometry, allele-specific oligonucleotide polymerase chain reaction, and next-generation sequencing of immunoglobulin and T-cell receptors.[30,31] Although a comparison of MRD methodologies is beyond the scope of this review, several comprehensive guides to ALL MRD have recently been published.[32,33]