Droplet Digital PCR Improves IG-/TR-based MRD Risk Definition in Childhood B-cell Precursor Acute Lymphoblastic Leukemia. Issue 3 (24th March 2021)

• Record Type: Journal Article
• Authors: Della Starza, Irene; Nunes, Vittorio; Lovisa, Federica; Silvestri, Daniela; Cavalli, Marzia; Garofalo, Andrea; Campeggio, Mimma; De Novi, Lucia Anna; Soscia, Roberta; Oggioni, Carlotta; Mussolin, Lara; Biondi, Andrea; Guarini, Anna; Valsecchi, Maria Grazia; Conter, Valentino; Biffi, Alessandra; Basso, Giuseppe; Foà, Robin; Cazzaniga, Giovanni
• Is Part Of: HemaSphere. Volume 5:Issue 3(2021)
• Page Start: e543
• Publication Date: 2021-03-24
• Subjects: Hematology -- Periodicals; 616.15005
• DOI: 10.1097/HS9.0000000000000543
• Languages: English
• ISSNs: 2572-9241

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : Minimal residual disease (MRD) is the most powerful prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Real-time quantitative polymerase chain reaction (RQ-PCR) represents the gold standard for molecular MRD assessment and risk-based stratification of front-line treatment. In the protocols of the Italian Association of Pediatric Hematology and Oncology (AIEOP) and the Berlin-Frankfurth-Munschen (BFM) group AIEOP-BFM ALL2009 and ALL2017, B-lineage ALL patients with high RQ-PCR-MRD at day+33 and positive at day+78 are defined slow early responders (SERs). Based on results of the AIEOP-BFM ALL2000 study, these patients are treated as high-risk also when positive MRD signal at day +78 is below the lower limit of quantification of RQ-PCR ("positive not-quantifiable, " POS-NQ). To assess whether droplet digital polymerase chain reaction (ddPCR) could improve patients' risk definition, we analyzed MRD in 209 pediatric B-lineage ALL cases classified by RQ-PCR as POS-NQ and/or negative (NEG) at days +33 and/or +78 in the AIEOP-BFM ALL2000 trial. ddPCR MRD analysis was performed on 45 samples collected at day +78 from SER patients, who had RQ-PCR MRD ≥ 5.0 × 10 –4 at day+33 and POS-NQ at day+78 and were treated as medium risk (MR). The analysis identified 13 of 45 positive quantifiable cases. Most relapses occurred in this patients' subgroup, while ddPCR NEG or ddPCR-POS-NQ patients had a significantly better outcome ( P < 0.001). Overall, in 112 MR cases and 52 standard-risk patients, MRD negativity and POS-NQ were confirmed by the ddPCR analysis except for a minority of cases, for whom no differences in outcome were registered. These data indicate that ddPCR is more accurate than RQ-PCR in the measurement of MRD, particularly in late follow-up time points, and may thus allow improving patients' stratification in ALL protocols.