Describing Sensitivity of ddPCR in Philadelphia-Positive ALL

In patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), digital droplet polymerase chain reaction (ddPCR) may be useful for monitoring minimal residual disease (MRD), an important prognostic factor in Ph+ ALL, according to new study findings published in Hematological Oncology.

The study, using a BCR/ABL1 assay, found that the novel method is able to detect MRD in a larger range of patients compared with quantitative real‐time PCR (Q-RT-PCR), the method currently used to detect MRD.

“To our knowledge, our study provides for the first time a recommendations for the use of ddPCR analysis for adult BCR/ABL1+ ALL cases, showing that ddPCR allows to recover the quantifiability of MRD in a large proportion of patients, who otherwise would fall into a nonquantifiable range of Q‐RT‐PCR, and launch the bases for using this approach also in Ph+ ALL,” explained the researchers.

In total, the researchers analyzed 98 samples, 10 of which were diagnostic samples and 88 of which were follow-up samples, coming from 40 Ph+ ALL cases. Samples came from patients enrolled in the GIMEMA LAL2116 trial, who received dasatinib plus steroids as induction therapy and blinatumomab as consolidation therapy.

Among 54 positive nonquantifiable (PNQ) samples, as determined by Q-RT-PCR in the study, ddPCR detected MRD in 29 while confirming 13 samples as PNQ and proving 12 to be negative. There were 24 negative samples based on Q-RT-PCR, of which 7 were deemed positive and quantifiable by ddPCR, 13 were confirmed to be negative, and 4 were determined to be PNQ.

“The study showed that ddPCR can reduce the proportion of PNQ samples, that represents a grey zone in the clinical practice, compared to [quantitative real-time PCR], increasing significantly the proportion of quantifiable samples (46% of cases; P < .0001),” emphasized the researchers. “Importantly, from a clinical standpoint, of the 7 samples—corresponding to 5 patients—that were negative by Q‐RT‐PCR and positive by ddPCR during follow‐up, 4/5 experienced a relapse (2 hematologic and 2 [central nervous system]).”

ddPCR has previously shown potential, compared with Q-RT-PCR, in lymphoma and Philadelphia-negative ALL, but prior to this study has rarely been studied in Ph+ ALL. The third-generation PCR, on top of being sensitive and accurate, is affordable and produces easily interpreted results, explained the researchers.

According to the researchers, ddPCR is also being used to detect T315I mutations, which carries a need for a “rapid switch in treatment” to avoid relapse. They note that based on this utilization of the technique, it may soon be used to improve the overall management of these patients with Ph+ ALL.

Reference

Ansuinelli M, Starza ID, Lauretti A, et al. Applicability of droplet digital polymerase chain reaction for minimal residual disease monitoring in Philadelphia‐positive acute lymphoblastic leukaemia. Hematol Oncol. Published online August 16, 2021. doi:10.1002/hon.2913