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Cancers
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Therapeutic Progress in Adult Acute Lymphoblastic Leukemia
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Therapeutic Progress in Adult Acute Lymphoblastic Leukemia

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (5 December 2022) | Viewed by 18338

Special Issue Editors

Prof. Dr. Renato Bassan

E-Mail Website
Guest Editor
Hematology Unit, Ospedale dell’Angelo, Mestre-Venezia, Italy
Interests: acute leukemia; minimal residual disease; risk stratification; treatment; risk-oriented therapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jose-Maria Ribera

E-Mail Website
Guest Editor
Clinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain
Interests: acute leukemia; minimal residual disease; risk stratification; treatment; risk-oriented therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute lymphoblastic leukemia (ALL) is a prototypic disseminated cancer, which, since the early 50s, has represented an almost ideal study model in hemato-oncology to support progress in diagnostics and therapeutics. At present, compared to early years, massive therapeutic progress has been achieved, more in children than adults. The turn of the century marked the new era of immunotherapy added to conventional chemotherapy and transplantation, leading to further improvement, while concurrent advances in molecular biology and genetics expanded our knowledge greatly about disease mechanisms and paved the way for risk/subset-oriented strategies and precision medicine. Thus, a long period of therapeutic stagnation in adult ALL therapy has ended, and recent trials document a global long-term survivorship of 50–60% for patients 18–60 years. Because these figures are still substantially lower than the 85–90% survival rate reported in children, and the data are much worse for the elderly patient population, many relevant issues remain to be addressed in adult ALL to improve their outcome. The panel of ALL experts who kindly accepted our invitation for this Special Issue was assembled to highlight many (if not all) of these aspects, from diagnosis to risk classification and risk- or subset-oriented therapy. It is hoped that their excellent work will be appreciated by all those interested in adult ALL therapy and wishing to focus on the major therapeutic advancements achieved in the past 20 years, and those interested in the more promising new experimental approaches likely to affect the management of adult ALL subsets in the years to come.          

Prof. Dr. Renato Bassan
Prof. Dr. Jose-Maria Ribera
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • acute lymphoblastic leukemia
  • Philadelphia-positive ALL
  • Philadelphia-like ALL
  • B-ALL
  • T-ALL
  • early-thymic precursor ALL
  • Burkitt leukemia
  • adolescent/young adult ALL
  • molecular genetics
  • minimal residual disease
  • risk stratification
  • risk-oriented therapy
  • immunotherapy
  • monoclonal antibody therapy
  • CAR-T cells
  • precision medicine
  • drug sensitivity screening

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Published Papers (4 papers)

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Review

23 pages, 1511 KiB  
Review
Optimal Use of Novel Immunotherapeutics in B-Cell Precursor ALL
by Federico Lussana, Gianluca Cavallaro, Pantaleo De Simone and Alessandro Rambaldi
Cancers 2023, 15(4), 1349; https://doi.org/10.3390/cancers15041349 - 20 Feb 2023
Cited by 3 | Viewed by 2915
Abstract
Novel immune therapies are currently being used for patients with R/R ALL based on their ability to induce not only hematologic but also molecular remission. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated [...] Read more.
Novel immune therapies are currently being used for patients with R/R ALL based on their ability to induce not only hematologic but also molecular remission. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated with a remarkably poor clinical outcome. Therefore, how to optimize the choice and the timing of such new treatments within different clinical settings remains a matter of debate. In addition, with the aim of increasing the rate and depth of molecular remission, clinical studies are currently evaluating the combination of these immunotherapies with chemotherapy in the contest of frontline treatment. The preliminary data suggest that this approach may increase the cure rate and perhaps reduce the use of allogeneic stem cell transplantation (alloHSCT) in first remission. In Ph-positive ALL, reproducible results are showing that frontline treatment programs, based on the combination of tyrosine kinase inhibitors and immunotherapy, can achieve unprecedented rates of hematologic and molecular remission as well as a long-term cure, even in the absence of chemotherapy and alloHSCT. The results from these studies have led to the development of potentially curative treatment modalities, even for older ALL patients who cannot be treated with conventional intensive chemotherapy. The present review examined the evidence for an appropriate use of the new immunotherapies in ALL patients and provided some appraisal of the current and future possible uses of these drugs for achieving further therapeutic improvement in the treatment of this disease. Full article
(This article belongs to the Special Issue Therapeutic Progress in Adult Acute Lymphoblastic Leukemia)
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16 pages, 2469 KiB  
Review
Optimizing Molecular Minimal Residual Disease Analysis in Adult Acute Lymphoblastic Leukemia
by Irene Della Starza, Lucia Anna De Novi, Loredana Elia, Vittorio Bellomarino, Marco Beldinanzi, Roberta Soscia, Deborah Cardinali, Sabina Chiaretti, Anna Guarini and Robin Foà
Cancers 2023, 15(2), 374; https://doi.org/10.3390/cancers15020374 - 6 Jan 2023
Cited by 9 | Viewed by 3210
Abstract
Minimal/measurable residual disease (MRD) evaluation has resulted in a fundamental instrument to guide patient management in acute lymphoblastic leukemia (ALL). From a methodological standpoint, MRD is defined as any approach aimed at detecting and possibly quantifying residual neoplastic cells beyond the sensitivity level [...] Read more.
Minimal/measurable residual disease (MRD) evaluation has resulted in a fundamental instrument to guide patient management in acute lymphoblastic leukemia (ALL). From a methodological standpoint, MRD is defined as any approach aimed at detecting and possibly quantifying residual neoplastic cells beyond the sensitivity level of cytomorphology. The molecular methods to study MRD in ALL are polymerase chain reaction (PCR) amplification-based approaches and are the most standardized techniques. However, there are some limitations, and emerging technologies, such as digital droplet PCR (ddPCR) and next-generation sequencing (NGS), seem to have advantages that could improve MRD analysis in ALL patients. Furthermore, other blood components, namely cell-free DNA (cfDNA), appear promising and are also being investigated for their potential role in monitoring tumor burden and response to treatment in hematologic malignancies. Based on the review of the literature and on our own data, we hereby discuss how emerging molecular technologies are helping to refine the molecular monitoring of MRD in ALL and may help to overcome some of the limitations of standard approaches, providing a benefit for the care of patients. Full article
(This article belongs to the Special Issue Therapeutic Progress in Adult Acute Lymphoblastic Leukemia)
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Figure 1

11 pages, 618 KiB  
Review
Modern Management Options for Ph+ ALL
by Josep-Maria Ribera and Sabina Chiaretti
Cancers 2022, 14(19), 4554; https://doi.org/10.3390/cancers14194554 - 20 Sep 2022
Cited by 5 | Viewed by 3434
Abstract
Impressive advances have been achieved in the management of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) since the initial concurrent use of imatinib and standard chemotherapy. The attenuation of chemotherapy has proven to be equally effective and less toxic, the use [...] Read more.
Impressive advances have been achieved in the management of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) since the initial concurrent use of imatinib and standard chemotherapy. The attenuation of chemotherapy has proven to be equally effective and less toxic, the use of third generation TKI upfront has improved the frequency of complete molecular response and the survival rate, and the combination of tyrosine kinase inhibitors with immunotherapy has further increased the rate of molecular response to 70–80% after consolidation, which has been translated into a survival rate of 75–90% in recent trials. As a result of these improvements, the role of allogeneic hematopoietic stem cell transplantation is being redefined. The methodology of measurable residual disease assessment and the detection of ABL1 mutations are also improving and will contribute to a more precise selection of the treatment for newly diagnosed and relapsed or refractory (R/R) patients. Finally, new compounds combined with immunotherapeutic approaches, including cellular therapy, are being used as rescue therapy and will hopefully be included in first line therapy in the near future. This article will review and update the modern management of patients with Ph+ ALL. Full article
(This article belongs to the Special Issue Therapeutic Progress in Adult Acute Lymphoblastic Leukemia)
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17 pages, 1400 KiB  
Review
Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets
by Eulàlia Genescà and Roberta la Starza
Cancers 2022, 14(8), 1873; https://doi.org/10.3390/cancers14081873 - 8 Apr 2022
Cited by 14 | Viewed by 7809
Abstract
A wide range of immature acute leukemias (AL), ranging from acute myeloid leukemias with minimal differentiation to acute leukemias with an ambiguous lineage, i.e., acute undifferentiated leukemias and mixed phenotype acute leukemia with T- or B-plus myeloid markers, cannot be definitely assigned to [...] Read more.
A wide range of immature acute leukemias (AL), ranging from acute myeloid leukemias with minimal differentiation to acute leukemias with an ambiguous lineage, i.e., acute undifferentiated leukemias and mixed phenotype acute leukemia with T- or B-plus myeloid markers, cannot be definitely assigned to a single cell lineage. This somewhat “grey zone” of AL expresses partly overlapping features with the most immature forms of T-cell acute lymphoblastic leukemia (T-ALL), i.e., early T-cell precursor ALL (ETP-ALL), near-ETP-ALL, and pro-T ALL. These are troublesome cases in terms of precise diagnosis because of their similarities and overlapping phenotypic features. Moreover, it has become evident that they share several genomic alterations, raising the question of how their phenotypes reflect distinct AL entities. The aim of this review was to provide a systematic overview of the genetic events associated with immature T-ALL and outline their relationship with treatment choices and outcomes, especially looking at the most recent preclinical and clinical studies. We wish to offer a basis for using the genetic information for new diagnostic algorithms, in order to better stratify patients and improve their management with more efficient and personalized therapeutic options. Understanding the genetic profile of this high-risk T-ALL subset is a prerequisite for changing the current clinical scenario. Full article
(This article belongs to the Special Issue Therapeutic Progress in Adult Acute Lymphoblastic Leukemia)
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