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Cancers
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Acute Leukemia in Older Adults - Is a Cure Possible?
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Acute Leukemia in Older Adults - Is a Cure Possible?

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

Deadline for manuscript submissions: closed (15 April 2021) | Viewed by 16074

Special Issue Editor

Prof. Dr. Bruno Quesnel

E-Mail Website
Guest Editor
Department of Hematology, CHU Lille, F-59000 Lille, France
Interests: leukemia; tumor dormancy; clonal hematopoiesis; PD-L1; immunoescape
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prognosis of acute leukemia has seen substantial improvements this last decade. Most of these advances came from better risk stratification and improved allogeneic transplant procedures. New therapeutics such as bispecific antibodies, TKI and IDH inhibitors, BH3 mimetics, and CAR-T cells will certainly improve prognosis in the coming years, but long-term follow-up is needed to firmly establish clinical benefits, notably for elderly patients. For this category of patient, little improvement has been seen. Comorbidities may in part explain this poor prognosis, but different clonal evolution in older adult patients compared to younger people resulting in more complex karyotype and molecular abnormalities is the key driver of primary therapeutic resistance and early relapse. Recent publications have shed light of the high prevalence of age-related clonal hematopoiesis in the common population and the specific risk of myeloid malignancies conferred by specific mutation, variant allele frequency, and clonal dynamics. The contribution of this clonal hematopoiesis to relapse, long-term persistence of minimal residual disease, and clonal evolution under new therapeutics are also under intense investigations. The role of the immune system in long-term control of minimal residual disease is suspected and could offer new opportunities of therapeutic development but has been less investigated.

This Special Issue of Cancers therefore encompasses new research articles and timely reviews on all aspects of acute leukemia and clonal evolution in elderly patients.

Prof. Bruno Quesnel
Guest Editor

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 short 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

  • leukemia
  • elderly
  • cure
  • MRD
  • new agents
  • relapse
  • clonal hematopoiesis

Published Papers (3 papers)

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Review

21 pages, 992 KiB  
Review
Trial Watch: Adoptive TCR-Engineered T-Cell Immunotherapy for Acute Myeloid Leukemia
by Diana Campillo-Davo, Sébastien Anguille and Eva Lion
Cancers 2021, 13(18), 4519; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184519 - 08 Sep 2021
Cited by 2 | Viewed by 3595
Abstract
Despite the advent of novel therapies, acute myeloid leukemia (AML) remains associated with a grim prognosis. This is exemplified by 5-year overall survival rates not exceeding 30%. Even with frontline high-intensity chemotherapy regimens and allogeneic hematopoietic stem cell transplantation, the majority of patients [...] Read more.
Despite the advent of novel therapies, acute myeloid leukemia (AML) remains associated with a grim prognosis. This is exemplified by 5-year overall survival rates not exceeding 30%. Even with frontline high-intensity chemotherapy regimens and allogeneic hematopoietic stem cell transplantation, the majority of patients with AML will relapse. For these patients, treatment options are few, and novel therapies are urgently needed. Adoptive T-cell therapies represent an attractive therapeutic avenue due to the intrinsic ability of T lymphocytes to recognize tumor cells with high specificity and efficiency. In particular, T-cell therapies focused on introducing T-cell receptors (TCRs) against tumor antigens have achieved objective clinical responses in solid tumors such as synovial sarcoma and melanoma. However, contrary to chimeric antigen receptor (CAR)-T cells with groundbreaking results in B-cell malignancies, the use of TCR-T cells for hematological malignancies is still in its infancy. In this review, we provide an overview of the status and clinical advances in adoptive TCR-T-cell therapy for the treatment of AML. Full article
(This article belongs to the Special Issue Acute Leukemia in Older Adults - Is a Cure Possible?)
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20 pages, 1327 KiB  
Review
Acute Myeloid Leukemia: Is It T Time?
by Meriem Ben Khoud, Tiziano Ingegnere, Bruno Quesnel, Suman Mitra and Carine Brinster
Cancers 2021, 13(10), 2385; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13102385 - 14 May 2021
Cited by 9 | Viewed by 3236
Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease driven by impaired differentiation of hematopoietic primitive cells toward myeloid lineages (monocytes, granulocytes, red blood cells, platelets), leading to expansion and accumulation of “stem” and/or “progenitor”-like or differentiated leukemic cells in the bone marrow and [...] Read more.
Acute myeloid leukemia (AML) is a heterogeneous disease driven by impaired differentiation of hematopoietic primitive cells toward myeloid lineages (monocytes, granulocytes, red blood cells, platelets), leading to expansion and accumulation of “stem” and/or “progenitor”-like or differentiated leukemic cells in the bone marrow and blood. AML progression alters the bone marrow microenvironment and inhibits hematopoiesis’ proper functioning, causing sustained cytopenia and immunodeficiency. This review describes how the AML microenvironment influences lymphoid lineages, particularly T lymphocytes that originate from the thymus and orchestrate adaptive immune response. We focus on the elderly population, which is mainly affected by this pathology. We discuss how a permissive AML microenvironment can alter and even worsen the thymic function, T cells’ peripheral homeostasis, phenotype, and functions. Based on the recent findings on the mechanisms supporting that AML induces quantitative and qualitative changes in T cells, we suggest and summarize current immunotherapeutic strategies and challenges to overcome these anomalies to improve the anti-leukemic immune response and the clinical outcome of patients. Full article
(This article belongs to the Special Issue Acute Leukemia in Older Adults - Is a Cure Possible?)
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Figure 1

19 pages, 372 KiB  
Review
Etiology of Acute Leukemia: A Review
by Cameron K. Tebbi
Cancers 2021, 13(9), 2256; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13092256 - 08 May 2021
Cited by 40 | Viewed by 8467
Abstract
Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of [...] Read more.
Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during preconception, pregnancy and throughout life, have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments, and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing but remain unexplained. Advances in genomic profiling, including genome-wide gene expression, DNA copy number and single nucleotide polymorphism (SNP) genotype, may shed some light on the role of genetics in these disparities. Separate two-hit hypotheses for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in the occurrence of leukemia requires further investigations. This review summarizes some of the above factors in acute lymphoblastic and myeloblastic leukemias and the direction for future research on the etiology of these disorders. Full article
(This article belongs to the Special Issue Acute Leukemia in Older Adults - Is a Cure Possible?)
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