Digital Droplet PCR Is a Reliable Tool to Improve Minimal Residual Disease Stratification in Adult Philadelphia-Negative Acute Lymphoblastic Leukemia

Starza, Irene Della; Novi, Lucia Anna De; Santoro, Alessandra; Salemi, Domenico; Spinelli, Orietta; Tosi, Manuela; Soscia, Roberta; Paoloni, Francesca; Cappelli, Luca Vincenzo; Cavalli, Marzia; Apicella, Valerio; Bellomarino, Vittorio; Lello, Eleonora Di; Vitale, Antonella; Vignetti, Marco; Fanfani, Francesco; Bassan, Renato; Guarini, Anna; Chiaretti, Sabina; Foà, Robin

doi:10.1016/j.jmoldx.2022.04.014

Cited by 7 publications

(10 citation statements)

References 24 publications

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“…However, most gene mutations are subclonal, and KIT mut is the one. Some studies have used NGS or dPCR to detect the mutant variant allele frequency of KIT mut after treatment and demonstrated their prognostic significance 8,9 . Currently, it remains unclear whether monitoring KIT mut transcript levels would have a prognostic significance.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have used NGS or dPCR to detect the mutant variant allele frequency of KIT mut after treatment and demonstrated their prognostic significance. 8,9 Currently, it remains unclear whether monitoring KIT mut transcript levels would have a prognostic significance. This study assessed the expression patterns of KIT mut transcript during treatment and found that it could be used to stratify t (8; 21) AML patients.…”

Section: Variablesmentioning

confidence: 99%

“…Fusion transcript levels detected using the real‐time quantitative reverse transcriptase‐polymerase chain reaction (RQ‐PCR) method have been recognized as the most useful means for MRD monitoring and are applied in clinical settings for AML 3,6,7 . Moreover, with the development of next‐generation sequencing (NGS) and digital polymerase chain reaction (dPCR) techniques, gene mutation detection is being increasingly applied for MRD monitoring 8–10 …”

Section: Introductionmentioning

confidence: 99%

“…with the development of next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR) techniques, gene mutation detection is being increasingly applied for MRD monitoring. [8][9][10] Although DNA is the predominant sample used in gene mutation testing, RNA could also be used, especially when monitoring MRD. 11,12 NPM1 mutation (A, B, and D type) transcript level tested using RQ-PCR is considered a representative, which was used for MRD monitoring during treatment in most reports and was found to be predictive of the clinical outcomes.…”

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confidence: 99%

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Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia

Sun,

Wang,

Chen

et al. 2024

Hematological Oncology

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In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut‐high (KIT_H) group and the KITmut‐low (KIT_L) group. The KIT_H patients showed significantly lower relapse‐free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3‐log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3‐log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3‐log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.

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Section: Discussionmentioning

confidence: 99%

Section: Variablesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia

Sun,

Wang,

Chen

et al. 2024

Hematological Oncology

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“…At present, the use of ddPCR and NGS to monitor MRD in the clinical practice is limited by the lack of international guidelines. Nevertheless, their application within clinical trials is progressively growing in lymphoid malignancies, such as Philadelphia-positive and -negative acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHL) ( 1 – 4 , 15 – 17 , 20 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Research Topic: Measurable Residual Disease in Hematologic Malignancies. Can digital droplet PCR improve measurable residual disease monitoring in chronic lymphoid malignancies?

Assanto

Giudice²,

Starza³

et al. 2023

Front. Oncol.

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Minimal/measurable residual disease (MRD) monitoring is progressively changing the management of hematologic malignancies. The possibility of detecting the persistence/reappearance of disease in patients in apparent clinical remission offers a refined risk stratification and a treatment decision making tool. Several molecular techniques are employed to monitor MRD, from conventional real-time quantitative polymerase chain reaction (RQ-PCR) to next generation sequencing and digital droplet PCR (ddPCR), in different tissues or compartments through the detection of fusion genes, immunoglobulin and T-cell receptor gene rearrangements or disease-specific mutations. RQ-PCR is still the gold standard for MRD analysis despite some limitations. ddPCR, considered the third-generation PCR, yields a direct, absolute, and accurate detection and quantification of low-abundance nucleic acids. In the setting of MRD monitoring it carries the major advantage of not requiring a reference standard curve built with the diagnostic sample dilution and of allowing to reduce the number of samples below the quantitative range. At present, the broad use of ddPCR to monitor MRD in the clinical practice is limited by the lack of international guidelines. Its application within clinical trials is nonetheless progressively growing both in acute lymphoblastic leukemia as well as in chronic lymphocytic leukemia and non-Hodgkin lymphomas. The aim of this review is to summarize the accumulating data on the use of ddPCR for MRD monitoring in chronic lymphoid malignancies and to highlight how this new technique is likely to enter into the clinical practice.

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Digital droplet PCR for T315I BCR::ABL1 KD mutation assessment in adult Ph-positive acute lymphoblastic leukemia with a minimal residual disease increase

Cardinali

Beldinanzi

Ansuinelli

et al. 2023

Leukemia & Lymphoma

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Digital Droplet PCR Is a Reliable Tool to Improve Minimal Residual Disease Stratification in Adult Philadelphia-Negative Acute Lymphoblastic Leukemia

Cited by 7 publications

References 24 publications

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia

Research Topic: Measurable Residual Disease in Hematologic Malignancies. Can digital droplet PCR improve measurable residual disease monitoring in chronic lymphoid malignancies?

Digital droplet PCR for T315I BCR::ABL1 KD mutation assessment in adult Ph-positive acute lymphoblastic leukemia with a minimal residual disease increase

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