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  1. Article: Measurable Residual Disease and Clonal Evolution in Acute Myeloid Leukemia from Diagnosis to Post-Transplant Follow-Up: The Role of Next-Generation Sequencing.

    Sperotto, Alessandra / Bochicchio, Maria Teresa / Simonetti, Giorgia / Buccisano, Francesco / Peccatori, Jacopo / Piemontese, Simona / Calistri, Elisabetta / Ciotti, Giulia / Pierdomenico, Elisabetta / De Marchi, Roberta / Ciceri, Fabio / Gottardi, Michele

    Biomedicines

    2023  Volume 11, Issue 2

    Abstract: It has now been ascertained that acute myeloid leukemias-as in most type of cancers-are mixtures of various subclones, evolving by acquiring additional somatic mutations over the course of the disease. The complexity of leukemia clone architecture and ... ...

    Abstract It has now been ascertained that acute myeloid leukemias-as in most type of cancers-are mixtures of various subclones, evolving by acquiring additional somatic mutations over the course of the disease. The complexity of leukemia clone architecture and the phenotypic and/or genotypic drifts that can occur during treatment explain why more than 50% of patients-in hematological remission-could relapse. Moreover, the complexity and heterogeneity of clone architecture represent a hindrance for monitoring measurable residual disease, as not all minimal residual disease monitoring methods are able to detect genetic mutations arising during treatment. Unlike with chemotherapy, which imparts a relatively short duration of selective pressure on acute myeloid leukemia clonal architecture, the immunological effect related to allogeneic hematopoietic stem cell transplant is prolonged over time and must be overcome for relapse to occur. This means that not all molecular abnormalities detected after transplant always imply inevitable relapse. Therefore, transplant represents a critical setting where a measurable residual disease-based strategy, performed during post-transplant follow-up by highly sensitive methods such as next-generation sequencing, could optimize and improve treatment outcome. The purpose of our review is to provide an overview of the role of next-generation sequencing in monitoring both measurable residual disease and clonal evolution in acute myeloid leukemia patients during the entire course of the disease, with special focus on the transplant phase.
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11020359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A successful treatment-free remission is achievable also by chronic myeloid leukemia patients lacking optimal requirements.

    Bonifacio, Massimiliano / Scaffidi, Luigi / Miggiano, Maria Cristina / Facchinelli, Davide / Tosoni, Luca / Pezone, Sara / Griguolo, Davide / Ciotti, Giulia / Danini, Marco / Bernardelli, Andrea / Bresciani, Rita / Cavraro, Monica / Crosera, Lara / De March, Elena / Dell'Eva, Michele / Dorotea, Laura / Frison, Luca / Furlani, Lara / Gianesello, Ilaria /
    Lovato, Ester / Marchetti, Elena / Morelli, Gianluca / Mullai, Rikard / Pizzano, Umberto / Zoletto, Simone / Fanin, Renato / Krampera, Mauro / Trentin, Livio / Calistri, Elisabetta / Carli, Giuseppe / Binotto, Gianni / Tiribelli, Mario

    Blood cancer journal

    2024  Volume 14, Issue 1, Page(s) 53

    MeSH term(s) Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid ; Chronic Disease ; Remission Induction ; Treatment Outcome ; Protein Kinase Inhibitors
    Chemical Substances Protein Kinase Inhibitors
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Letter
    ZDB-ID 2600560-8
    ISSN 2044-5385 ; 2044-5385
    ISSN (online) 2044-5385
    ISSN 2044-5385
    DOI 10.1038/s41408-024-01025-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: EUTOS score predicts early optimal response to imatinib according to the revised 2013 ELN recommendations.

    Bonifacio, Massimiliano / Binotto, Gianni / Calistri, Elisabetta / Maino, Elena / Tiribelli, Mario

    Annals of hematology

    2014  Volume 93, Issue 1, Page(s) 163–164

    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Benzamides/therapeutic use ; Female ; Fusion Proteins, bcr-abl/antagonists & inhibitors ; Fusion Proteins, bcr-abl/blood ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Male ; Middle Aged ; Piperazines/therapeutic use ; Practice Guidelines as Topic ; Prognosis ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; Young Adult
    Chemical Substances Antineoplastic Agents ; Benzamides ; Piperazines ; Protein Kinase Inhibitors ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
    Language English
    Publishing date 2014-01
    Publishing country Germany
    Document type Letter
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-013-1974-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the "GRUPPO TRIVENETO LMC".

    Di Giusto, Sara / Toffoletti, Eleonora / Bonifacio, Massimiliano / Binotto, Gianni / Miggiano, Maria Cristina / Calistri, Elisabetta / Stulle, Manuela / Ermacora, Anna / Stella, Rossella / Scaffidi, Luigi / D'Amore, Fabio / Scotton, Giorgia / Griguolo, Davide / De Matteis, Giovanna / Bertorelle, Roberta / Krampera, Mauro / Semenzato, Gianpietro / Fanin, Renato / Damiani, Daniela /
    Tiribelli, Mario

    Cancer medicine

    2022  Volume 12, Issue 3, Page(s) 3180–3184

    Abstract: We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. ... ...

    Abstract We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087.
    MeSH term(s) Humans ; Imatinib Mesylate ; Fusion Proteins, bcr-abl/genetics ; Protein Kinase Inhibitors/pharmacology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Remission Induction
    Chemical Substances Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Protein Kinase Inhibitors
    Language English
    Publishing date 2022-10-08
    Publishing country United States
    Document type Letter
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.5158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Making Treatment-Free Remission (TFR) Easier in Chronic Myeloid Leukemia: Fact-Checking and Practical Management Tools.

    Castagnetti, Fausto / Binotto, Gianni / Capodanno, Isabella / Billio, Atto / Calistri, Elisabetta / Cavazzini, Francesco / Crugnola, Monica / Gozzini, Antonella / Gugliotta, Gabriele / Krampera, Mauro / Lucchesi, Alessandro / Merli, Anna / Miggiano, Maria Cristina / Minotto, Claudia / Poggiaspalla, Monica / Salvucci, Marzia / Scappini, Barbara / Tiribelli, Mario / Trabacchi, Elena /
    Rosti, Gianantonio / Galimberti, Sara / Bonifacio, Massimiliano

    Targeted oncology

    2021  Volume 16, Issue 6, Page(s) 823–838

    Abstract: In chronic-phase chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are the standard of care, and treatment-free remission (TFR) following the achievement of a stable deep molecular response (DMR) has become, alongside survival, a primary ... ...

    Abstract In chronic-phase chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are the standard of care, and treatment-free remission (TFR) following the achievement of a stable deep molecular response (DMR) has become, alongside survival, a primary goal for virtually all patients. The GIMEMA CML working party recently suggested that the possibility of achieving TFR cannot be denied to any patient, and proposed specific treatment policies according to the patient's age and risk. However, other international recommendations (including 2020 ELN recommendations) are more focused on survival and provide less detailed suggestions on how to choose first and subsequent lines of treatment. Consequently, some grey areas remain. After literature review, a panel of Italian experts discussed the following controversial issues: (1) early prediction of DMR and TFR: female sex, non-high disease risk score, e14a2 transcript and early MR achievement have been associated with stable DMR, but the lack of these criteria is not sufficient to exclude any patient from TFR; (2) criteria for first and subsequent line therapy choice: a number of patient and drug characteristics have been proposed to make a personalized decision; (3) monitoring of residual disease after discontinuation: after the first 6 months, the frequency of molecular tests can be reduced based on MR4.5 persistence and short turnaround time; (4) prognosis of TFR: therapy and DMR duration are important to predict TFR; although immunological control of CML plays a role, no immunological predictive phenotype is currently available. This guidance is intended as a practical tool to support physicians in decision making.
    MeSH term(s) Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Prognosis ; Protein Kinase Inhibitors/therapeutic use ; Remission Induction ; Treatment Outcome
    Chemical Substances Protein Kinase Inhibitors
    Language English
    Publishing date 2021-10-18
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2222136-0
    ISSN 1776-260X ; 1776-2596
    ISSN (online) 1776-260X
    ISSN 1776-2596
    DOI 10.1007/s11523-021-00831-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Imatinib-treated chronic myeloid leukemia patients with discordant response between cytogenetic and molecular tests at 3 and 6 month time-points have a reduced probability of subsequent optimal response.

    Bonifacio, Massimiliano / Binotto, Gianni / Maino, Elena / Calistri, Elisabetta / Marin, Luciana / Scaffidi, Luigi / Frison, Luca / De Marchi, Federico / Krampera, Mauro / Semenzato, Giampiero / Fanin, Renato / Ambrosetti, Achille / Tiribelli, Mario

    Haematologica

    2015  Volume 100, Issue 8, Page(s) e299–301

    MeSH term(s) Antineoplastic Agents/therapeutic use ; Chromosome Aberrations ; Fusion Proteins, bcr-abl/genetics ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality ; Protein Kinase Inhibitors/therapeutic use ; Retrospective Studies ; Time Factors ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
    Language English
    Publishing date 2015-08
    Publishing country Italy
    Document type Letter
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2015.124685
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Combination of EUTOS score and 3-month BCR-ABL transcript level identifies a group of good-risk chronic myeloid leukemia patients with favorable response to frontline imatinib therapy.

    Tiribelli, Mario / Binotto, Gianni / Calistri, Elisabetta / Maino, Elena / Scaffidi, Luigi / Medeot, Marta / Nabergoj, Mitja / Ambrosetti, Achille / Semenzato, Gianpietro / Fanin, Renato / Bonifacio, Massimiliano

    American journal of hematology

    2015  Volume 90, Issue 7, Page(s) E135–7

    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Benzamides/therapeutic use ; Drug Monitoring ; Female ; Fusion Proteins, bcr-abl/genetics ; Gene Expression ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality ; Male ; Middle Aged ; Piperazines/therapeutic use ; Prognosis ; Prospective Studies ; Pyrimidines/therapeutic use ; RNA, Messenger/genetics ; Risk ; Survival Analysis ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Benzamides ; Piperazines ; Pyrimidines ; RNA, Messenger ; Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
    Language English
    Publishing date 2015-07
    Publishing country United States
    Document type Letter
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.24022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients.

    Tiribelli, Mario / Bonifacio, Massimiliano / Binotto, Gianni / Iurlo, Alessandra / Cibien, Francesca / Maino, Elena / Guella, Anna / Festini, Gianluca / Minotto, Claudia / De Biasi, Ercole / De Marchi, Federico / Scaffidi, Luigi / Frison, Luca / Bucelli, Cristina / Medeot, Marta / Calistri, Elisabetta / Sancetta, Rosaria / Stulle, Manuela / Orofino, Nicola /
    Krampera, Mauro / Gherlinzoni, Filippo / Semenzato, Gianpietro / Pizzolo, Giovanni / Ambrosetti, Achille / Fanin, Renato

    Oncotarget

    2018  Volume 9, Issue 18, Page(s) 14219–14227

    Abstract: Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing ... ...

    Abstract Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (
    Language English
    Publishing date 2018-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.24478
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: EUTOS score predicts long-term outcome but not optimal response to imatinib in patients with chronic myeloid leukaemia.

    Tiribelli, Mario / Bonifacio, Massimiliano / Calistri, Elisabetta / Binotto, Gianni / Maino, Elena / Marin, Luciana / Guardalben, Emanuele / Branca, Antonio / Gherlinzoni, Filippo / Semenzato, Gianpietro / Sancetta, Rosaria / Pizzolo, Giovanni / Fanin, Renato

    Leukemia research

    2013  Volume 37, Issue 11, Page(s) 1457–1460

    Abstract: To test the recently developed EUTOS score in predicting optimal response to imatinib and the long-term outcome, 265 patients with early chronic phase chronic myeloid leukaemia treated with standard dose imatinib were analysed. Achievement of optimal ... ...

    Abstract To test the recently developed EUTOS score in predicting optimal response to imatinib and the long-term outcome, 265 patients with early chronic phase chronic myeloid leukaemia treated with standard dose imatinib were analysed. Achievement of optimal response endpoints were higher in low-risk patients, though the difference was not statistically significant: PCyR at 6th month 86% vs 67% (p=0.06), CCyR at 12th month 80% vs 63% (p=0.09), MMR at 18th month 61% vs 36% (p=0.11). However, EUTOS score was predictive for the long-term response. With a median follow-up of 61 months, 53% high-risk patients experienced imatinib failure, compared to 23% in the low-risk group (p=0.013). Among high-risk patients, 4/17 (23%) progressed to accelerated/blastic phase or died, compared to 11/248 (5%) low-risk patients, with 5-year progression-free survival rates of 84±10% and 96±1%, respectively (p=0.04). Our data confirm that EUTOS score envisions the long-term outcome of imatinib therapy.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Benzamides/therapeutic use ; Biomarkers, Tumor/analysis ; Diagnostic Techniques and Procedures ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality ; Male ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/therapy ; Piperazines/therapeutic use ; Prognosis ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Retrospective Studies ; Risk Assessment ; Survival Rate ; Young Adult
    Chemical Substances Benzamides ; Biomarkers, Tumor ; Piperazines ; Protein Kinase Inhibitors ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B)
    Language English
    Publishing date 2013-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 752396-8
    ISSN 1873-5835 ; 0145-2126
    ISSN (online) 1873-5835
    ISSN 0145-2126
    DOI 10.1016/j.leukres.2013.07.037
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  10. Article: Biological and clinical features of T-biphenotypic acute leukaemia: report from a single centre.

    Tiribelli, Mario / Damiani, Daniela / Masolini, Paola / Candoni, Anna / Calistri, Elisabetta / Fanin, Renato

    British journal of haematology

    2004  Volume 125, Issue 6, Page(s) 814–815

    MeSH term(s) Acute Disease ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Female ; Humans ; Leukemia, Myeloid/complications ; Leukemia, Myeloid/drug therapy ; Leukemia-Lymphoma, Adult T-Cell/complications ; Leukemia-Lymphoma, Adult T-Cell/drug therapy ; Male ; Middle Aged
    Language English
    Publishing date 2004-06
    Publishing country England
    Document type Case Reports ; Comment ; Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/j.1365-2141.2004.04969.x
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