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ddPCR, NGS “Are Promising Alternative Approaches to MRD Assessment in ALL”

Digital droplet PCR (ddPCR) and next-generation sequencing (NGS) “appear to be feasible and attractive alternative approaches for MRD assessment” that are both more sensitive and more accurate than current standard PCR amplification-based methods, and the combined use of these approaches “could provide an accurate MRD analysis for virtually all patients,” according to the authors of a review of emerging technologies for the molecular monitoring of MRD in acute lymphoblastic leukemia (ALL).

Compared with current methods, ddPCR and NGS “can better discriminate critical samples” by real-world quantitative PCR analysis, especially in subsets that often lack a sensitive molecular marker, such as early T-ALL and pro-B ALL, write co-senior authors Anna Guarini, PhD, and Robin Foà, MD, and colleagues at Sapienza University in Rome. The review was published in Cancers in January.

Circulating-tumor DNA (ctDNA) may “provide a more comprehensive molecular overview of the genetic heterogeneity of a given tumor at presentation” and may enable sequential blood testing during the disease course, the authors write. They note, however, that for this approach to become a useful tool for molecular analysis, “several preanalytic factors” affecting ctDNA amount and quality “need to be overcome.”

The authors conclude by expressing concern that the current trend toward more personalized treatment strategies for ALL requires that patient management become ever more laboratory-driven. While “this complex approach is paramount in order to offer optimal management to ALL patients and to increase the likelihood of a cure,” they question whether this approach is “doable” worldwide.

• Della Starza I, De Novi LA, Elia L, et al. Optimizing Molecular Minimal Residual Disease Analysis in Adult Acute Lymphoblastic Leukemia. Cancers (Basel). 2023;15(2):374. Published 2023 Jan 6. doi:10.3390/cancers15020374