Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation
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- Simona Bernardi
- Unit of Blood Diseases and Stem Cell Transplantation, DPT of Clinical and Experimental Sciences University of Brescia, ASST Spedali Civili di Brescia Brescia Italy
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- Michele Malagola
- Unit of Blood Diseases and Stem Cell Transplantation, DPT of Clinical and Experimental Sciences University of Brescia, ASST Spedali Civili di Brescia Brescia Italy
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- Camilla Zanaglio
- Unit of Blood Diseases and Stem Cell Transplantation, DPT of Clinical and Experimental Sciences University of Brescia, ASST Spedali Civili di Brescia Brescia Italy
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- Nicola Polverelli
- Unit of Blood Diseases and Stem Cell Transplantation, DPT of Clinical and Experimental Sciences University of Brescia, ASST Spedali Civili di Brescia Brescia Italy
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- Elif Dereli Eke
- Unit of Blood Diseases and Stem Cell Transplantation, DPT of Clinical and Experimental Sciences University of Brescia, ASST Spedali Civili di Brescia Brescia Italy
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- Mariella D’Adda
- Division of Hematology ASST Spedali Civili of Brescia Brescia Italy
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- Mirko Farina
- Division of Hematology ASST Spedali Civili of Brescia Brescia Italy
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- Cristina Bucelli
- Hematology Division Foundation IRCCS Ca' Granda‐Ospedale Maggiore Policlinico Milan Italy
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- Luigi Scaffidi
- Department of Medicine, Section of Hematology University of Verona Verona Italy
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- Eleonora Toffoletti
- Division of Hematology and Bone Marrow Transplantation, Department of Medical Area University of Udine Udine Italy
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- Clara Deambrogi
- Division of Hematology, Department of Translational Medicine University of Eastern Piedmont Novara Italy
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- Fabio Stagno
- Hematology Section and BMT Unit Rodolico Hospital A.O.U. Policlinico – V. Emanuele Catania Italy
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- Micaela Bergamaschi
- Clinical Hematology, Dipartimento Terapie Oncologiche Integrate Ospedale Policlinico San Martino Genova Italy
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- Luca Franceschini
- Department of Biomedicine and Prevention The University Tor Vergata Rome Italy
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- Elisabetta Abruzzese
- Division of Hematology S. Eugenio Hospital Roma Italy
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- Maria Domenica Divona
- Department of Biomedicine and Prevention The University Tor Vergata Rome Italy
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- Marco Gobbi
- Clinical Hematology, Dipartimento Terapie Oncologiche Integrate Ospedale Policlinico San Martino Genova Italy
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- Francesco Di Raimondo
- Hematology Section and BMT Unit Rodolico Hospital A.O.U. Policlinico – V. Emanuele Catania Italy
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- Gianluca Gaidano
- Division of Hematology, Department of Translational Medicine University of Eastern Piedmont Novara Italy
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- Mario Tiribelli
- Division of Hematology and Bone Marrow Transplantation, Department of Medical Area University of Udine Udine Italy
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- Massimiliano Bonifacio
- Department of Medicine, Section of Hematology University of Verona Verona Italy
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- Chiara Cattaneo
- Division of Hematology ASST Spedali Civili of Brescia Brescia Italy
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- Alessandra Iurlo
- Hematology Division Foundation IRCCS Ca' Granda‐Ospedale Maggiore Policlinico Milan Italy
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- Domenico Russo
- Unit of Blood Diseases and Stem Cell Transplantation, DPT of Clinical and Experimental Sciences University of Brescia, ASST Spedali Civili di Brescia Brescia Italy
説明
<jats:title>Abstract</jats:title><jats:p>Treatment‐free remission (TFR) by tyrosine kinase inhibitors (TKI) discontinuation in patients with deep molecular response (DMR) is a paramount goal in the current chronic myeloid leukemia (CML) therapeutic strategy. The best DMR level by real‐time quantitative PCR (RT‐qPCR) for TKI discontinuation is still a matter of debate. To compare the accuracy of digital PCR (dPCR) and RT‐qPCR for <jats:italic>BCR‐ABL1</jats:italic> transcript levels detection, 142 CML patients were monitored for a median time of 24 months. Digital PCR detected <jats:italic>BCR‐ABL1 </jats:italic>transcripts in the RT‐qPCR undetectable cases. The dPCR analysis of the samples, grouped by the MR classes, revealed a significant difference between MR<jats:sup>4.0</jats:sup> and MR<jats:sup>4.5</jats:sup> (<jats:italic>P</jats:italic> = 0.0104) or MR<jats:sup>5.0</jats:sup> (<jats:italic>P</jats:italic> = 0.0032). The clinical and hematological characteristics of the patients grouped according to DMR classes (MR<jats:sup>4.0</jats:sup> vs MR<jats:sup>4.5‐5.0</jats:sup>) were superimposable. Conversely, patients with dPCR values <0.468 <jats:italic>BCR‐ABL1</jats:italic> copies/µL (as we previously described) showed a longer DMR duration (<jats:italic>P</jats:italic> = 0.0220) and mainly belonged to MR<jats:sup>4.5‐5.0</jats:sup> (<jats:italic>P</jats:italic> = 0.0442) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment; among the 111 patients, 24 (22%) lost the MR<jats:sup>3.0 </jats:sup>or MR<jats:sup>4.0</jats:sup>. RT‐qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation (<jats:italic>P</jats:italic> = 0.8100). On the contrary, according to dPCR, 12/25 (48%) patients with <jats:italic>BCR‐ABL1</jats:italic> values ≥0.468 and 12/86 (14%) patients with <jats:italic>BCR‐ABL1</jats:italic> values <0.468 lost DMR in this cohort, respectively (<jats:italic>P</jats:italic> = 0.0003). Treatment‐free remission of patients who discontinued TKI with a dPCR <0.468 was significantly higher compared to patients with dPCR ≥ 0.468 (TFR at 2 years 83% vs 52% <jats:italic>P</jats:italic> = 0.0017, respectively). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation.</jats:p>
収録刊行物
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- Cancer Medicine
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Cancer Medicine 8 (5), 2041-2055, 2019-04-04
Wiley