Memorial Issue Dedicated to Prof. Dr. Michele Baccarani: An Excellent Hematologist on Chronic Myeloid Leukemia

A special issue of Hemato (ISSN 2673-6357). This special issue belongs to the section "Leukemias".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 16820

Special Issue Editors


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Guest Editor
Unit of Blood Diseases and Bone Marrow Transplantation, DPT of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25121 Brescia, Italy
Interests: prognosis and therapy of chronic myeloid leukemia; biology and therapy of acute leukemias; stem cell transplantation; CAR-T therapy; stem cell biology; regenerative medicine
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Guest Editor
IRST/IRCCS "Dino Amadori", Meldola (FC), Italy
Interests: chronic myeloid leukemia

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Guest Editor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy
Interests: autologous and allogeneic stem cell transplantation; graft-versus-host disease and other post-transplant complications; myelodysplastic syndromes; chronic myelomonocytic leukemia and other myelodysplastic/myeloproliferative neoplasms; myeloproliferative neoplasms; cutaneous T-cell lymphomas; autologous transplantation in autoimmune diseases
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Centre for Haematology, Department of Immunology and Inflammation, Imperial College, London W12 0NN, UK
Interests: chronic myeloid leukemia

Special Issue Information

Dear Colleagues,

This Special Issue aims to honor the outstanding scientific career of Prof. Michele Baccarani. I knew Prof. Baccarani forty years ago, and during this time I had the privilege and the honor to work with him and to share the passion for studying biology, the prognosis and therapy of CML. Pr Baccarani together with Pr Sante Tura founded the Italian Cooperative Study Group on CML, around 1980, and promoted in Italy the most important Trials on CML treatment: from splenectomy to bone marrow transplantation, and lately from interferon alpha to the tyrosine kinase inhibitors (TKIs) (Blood. 2002 Mar 1;99(5):1527-35; N Engl J Med. 2010 Jun 17;362(24):2260–2270). He was also a founding member of the European CML Group and greatly contributed to the European Leukemia Net Guidelines on CML (Clin Oncol. 2009 Dec 10;27(35):6041-51.) Thanks to his brilliant intelligence, scientific rigor, incessant work, passion and, moreover, intellectual honesty, Michele Baccarani greatly contributed to transforming CML from a lethal disease to chronic disease. His dream was to cure the CML and in part, it succeeded. TKIs can avoid the acute leukemia progression of CML and allow the survival of CML patients almost equal to the survival of a healthy population.

We invite contributions from leading figures who have either personally known Prof. Michele Baccarani or been inspired by his pioneering scientific research, thereby remembering and honoring not only a great scientist but also a great man which has left a mark in the lives of many people.

Prof. Domenico Russo
Prof. Dr. Gianantonio Rosti
Dr. Francesco Onida
Prof. Dr. Jane Apperley
Guest Editors

Manuscript Submission Information

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Keywords

  • Ph+ cell biology
  • CML modelling 
  • CML prognosis 
  • BCR-ABL1 detection and quantitation 
  • BCR-ABL1 minimal residual disease 
  • target drugs
  • therapy discontinuation 
  • TFR
  • de-escalation treatment 
  • pregnancy in CML
  • quality of life

Published Papers (6 papers)

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Review

9 pages, 560 KiB  
Review
The Role of Allogeneic Transplantation in Chronic Myeloid Leukemia in 2023: A Case-Based Concise Review
by Mario Tiribelli, Giuseppe Petruzzellis, Giulia Battaglia, Martina Pucillo, Marta Lisa Battista, Michela Cerno, Antonella Geromin, Gabriele Facchin, Umberto Pizzano, Daniela Damiani, Renato Fanin and Francesca Patriarca
Hemato 2023, 4(3), 250-258; https://doi.org/10.3390/hemato4030020 - 15 Aug 2023
Viewed by 1255
Abstract
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), granting patients a life expectancy close to that of the normal population and, in a subset of patients, the possibility to discontinue therapy. Nonetheless, for a not negligible minority of [...] Read more.
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), granting patients a life expectancy close to that of the normal population and, in a subset of patients, the possibility to discontinue therapy. Nonetheless, for a not negligible minority of patients, TKIs are not able to control CML. Allogeneic hematopoietic cell transplantation (HCT) has long been a pivotal therapy for CML. At present, allogeneic HCT is considered an option in CML patients diagnosed or progressing to blast phase (BP), for those in chronic phase (CP) resistant to multiple lines of TKI therapy or for those experiencing severe toxicity, mostly hematologic, under TKIs. Moving from real-world cases, we reviewed the results of allogeneic HCT in the setting of advanced-phase CML or failure of TKIs, with a focus on the progresses in transplant technology that has extended transplant options in elderly CML patients and in those lacking a sibling donor, and on the post-HCT strategies for prevention and treatment of disease relapse. Full article
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20 pages, 1457 KiB  
Review
The Direct and Indirect Effects of Tyrosine Kinase Inhibitors on the Cardiovascular System in Chronic Myeloid Leukemia
by Alessandro Costa, Raimondo Pittorru, Giovanni Caocci, Federico Migliore, Francesco Tona, Olga Mulas and Giorgio La Nasa
Hemato 2023, 4(3), 207-226; https://doi.org/10.3390/hemato4030017 - 14 Jul 2023
Viewed by 1713
Abstract
Since their introduction, tyrosine kinase inhibitors (TKIs) have radically changed the treatment paradigm of Chronic Myeloid Leukemia (CML), leading to deep and lasting molecular responses and profoundly influencing survival. However, cancer-therapy-related Cardiovascular Toxicities (CTR-CVTs) associated with BCR::ABL1 TKIs are one of the main [...] Read more.
Since their introduction, tyrosine kinase inhibitors (TKIs) have radically changed the treatment paradigm of Chronic Myeloid Leukemia (CML), leading to deep and lasting molecular responses and profoundly influencing survival. However, cancer-therapy-related Cardiovascular Toxicities (CTR-CVTs) associated with BCR::ABL1 TKIs are one of the main sources of concern: hypertension, arterial occlusive events, arrhythmias, dysmetabolic alteration, and glomerular filtration impairment are frequently reported in clinical trials and real-life experiences. Therefore, a close interaction between hematologists and cardiologists becomes crucial to implementing prevention protocols based on a comprehensive assessment of baseline cardiovascular risk, the management of any detectable and modifiable risk factors, and the elaboration of a monitoring plan for CTR-CVTs during treatment. Here, we provide the most comprehensive and recent evidence in the literature on the pathophysiological patterns underlying CTR-CVTs, providing useful evidence-based guidance on the prevention and management of CVD risk factors at baseline and during treatment with BCR::ABL1 TKIs. Full article
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8 pages, 249 KiB  
Review
Cardiotoxicity of Tyrosine Kinase Inhibitors in Philadelphia-Positive Leukemia Patients
by Adriatik Berisha, Angelo Placci and Pier Paolo Piccaluga
Hemato 2023, 4(1), 68-75; https://doi.org/10.3390/hemato4010007 - 27 Feb 2023
Viewed by 1828
Abstract
In the past twenty years, tyrosine kinase inhibitors (TKIs) have substantially changed the therapeutic landscape and the clinical outcome of several cancers, including Philadelphia-chromosome positive chronic myeloid leukemia and acute lymphoblastic leukemia, chronic eosinophilic syndromes, gastrointestinal stromal tumors, and others. Despite the obvious [...] Read more.
In the past twenty years, tyrosine kinase inhibitors (TKIs) have substantially changed the therapeutic landscape and the clinical outcome of several cancers, including Philadelphia-chromosome positive chronic myeloid leukemia and acute lymphoblastic leukemia, chronic eosinophilic syndromes, gastrointestinal stromal tumors, and others. Despite the obvious advantages offered in terms of efficacy and the overall safety profile, this new class of agents presents novel side effects, sometimes different from those induced by conventional chemotherapy. Among others, the potential cardiac toxicity, characterized by possible arrhythmias and the highest rates of cardiac ischemic disease and heart failure, were predominantly investigated. In this article, the authors review the most significant evidence in this regard, highlighting the overall benefit of TKI usage and the need for careful monitoring, especially in elderly patients. Full article
11 pages, 822 KiB  
Review
Digital PCR as a New Method for Minimal Residual Disease Monitoring and Treatment Free Remission Management in Chronic Myeloid Leukemia Patients: Is It Reliable?
by Simona Bernardi, Michele Malagola, Mirko Farina, Nicola Polverelli, Federica Re and Domenico Russo
Hemato 2023, 4(1), 1-11; https://doi.org/10.3390/hemato4010001 - 30 Dec 2022
Cited by 3 | Viewed by 2257
Abstract
The effective and sensitive monitoring of Minimal Residual Disease or Measurable Residual Disease (MRD) is a very important aspect in the management of patients affected by hematologic malignancies. The recent availability of new technologies has opened to the improvement of MRD monitoring. It [...] Read more.
The effective and sensitive monitoring of Minimal Residual Disease or Measurable Residual Disease (MRD) is a very important aspect in the management of patients affected by hematologic malignancies. The recent availability of new technologies has opened to the improvement of MRD monitoring. It is particularly relevant in patients affected by Chronic Myeloid Leukemia (CML). MRD monitoring is key in the management of CML patients thanks to the efficacy of TKIs therapy. Moreover, the policies of TKIs discontinuation aimed at treatment free remission are strongly based on the good selection of patients eligible for stopping TKIs therapy. The recently described application of digital PCR in CML patients monitoring seems to improve the accuracy and precision in the identification of optimal responders. The present review reports an overview on the application of digital PCR in the monitoring of MRD in CML and its impact on TKIs discontinuation trials and, consequently, on TFR success. Full article
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16 pages, 648 KiB  
Review
TP53 Mutant Acute Myeloid Leukemia: The Immune and Metabolic Perspective
by Federico Zingarelli, Letizia Zannoni and Antonio Curti
Hemato 2022, 3(4), 742-757; https://doi.org/10.3390/hemato3040050 - 15 Nov 2022
Viewed by 5720
Abstract
TP53 mutated/deleted acute myeloid leukemia (AML) stands out as one of the poorest prognosis forms of acute leukemia with a median overall survival not reaching one year in most cases, even in selected cases when allogenic stem-cell transplantation is performed. This aggressive behavior [...] Read more.
TP53 mutated/deleted acute myeloid leukemia (AML) stands out as one of the poorest prognosis forms of acute leukemia with a median overall survival not reaching one year in most cases, even in selected cases when allogenic stem-cell transplantation is performed. This aggressive behavior relies on intrinsic chemoresistance of blast cells and on high rates of relapse. New insights into the biology of the disease have shown strong linkage between TP53 mutant AML, altered metabolic features and immunoregulation uncovering new scenarios and leading to possibilities beyond current treatment approaches. Furthermore, new targeted therapies acting on misfolded/dysfunctional p53 protein are under current investigation with the aim to improve outcomes. In this review, we sought to offer an insight into TP53 mutant AML current biology and treatment approaches, with a special focus on leukemia-associated immune and metabolic changes. Full article
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13 pages, 298 KiB  
Review
Update in Childhood Chronic Myeloid Leukemia
by Fiorina Giona and Simona Bianchi
Hemato 2022, 3(4), 718-730; https://doi.org/10.3390/hemato3040048 - 5 Nov 2022
Cited by 2 | Viewed by 2683
Abstract
Chronic myeloid leukemia (CML) in childhood represents only 3% of newly diagnosed pediatric leukemia. The diagnostic hallmark of CML is the Philadelphia (Ph) chromosome, which derives from the fusion of the ABL1-oncogene located on chromosome 9 to the breakpoint cluster region ( [...] Read more.
Chronic myeloid leukemia (CML) in childhood represents only 3% of newly diagnosed pediatric leukemia. The diagnostic hallmark of CML is the Philadelphia (Ph) chromosome, which derives from the fusion of the ABL1-oncogene located on chromosome 9 to the breakpoint cluster region (BCR) gene on chromosome 22, resulting in a constitutively dysregulated ABL1 tyrosine kinase, either as 210 kDa or 190 kDa. Depending on the localization of the breakpoint site within the major BCR region, the majority of CML patients exhibit transcripts with either the b3a2 or b2a2 junction, or both. Several questions are still open with regard to childhood CML, especially concerning the biologic and clinical features of the disease, and the treatment of choice for pediatric patients with CML. Moreover, over the last few years, several tyrosine kinase inhibitors (TKIs) have been available for children and adolescents with CML, and current clinical practice investigates what the effective and optimal doses of TKIs are in these two categories of patients. The use of TKIs in pediatric patients with CML has also opened up questions on the following items: (1) the long-term effects of these drugs on children; (2) the management of pediatric CML forms resistant or intolerant to TKIs; (3) the monitoring of disease outcomes during treatment; (4) and the right timing to discontinue therapy. Despite the efficacy of TKIs also in the pediatric population, the potential late adverse effects, and the drug resistance, leave open the possibility of allogeneic hematopoietic stem cell transplantation as a treatment option in pediatric CML. Published data and personal experiences regarding these issues will be analyzed and discussed. Full article
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