Special Issue "Advances in Acute Myeloid Leukemia"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: 31 May 2020.

Special Issue Editors

Dr. Sébastien Anguille
Website
Guest Editor
1. Antwerp University Hospital, Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp, Belgium;
2. University of Antwerp, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group, Antwerp, Belgium
Interests: acute myeloid leukemia; immunotherapy; dendritic cell vaccines; CAR-T cells
Dr. Roland B. Walter
Website
Co-Guest Editor
Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Interests: acute myeloid leukemia; CD33; clinical trials; immunotherapy
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The prognosis of adult patients with acute myeloid leukemia (AML) remains poor. The 5-year overall survival rate of AML is approximately 25%, a statistic that has largely remained unchanged over the last decades. In recent years, we have witnessed the advent of several new treatments including targeted therapies, monoclonal antibodies and other immunotherapies. The rapid discovery of novel treatments along with advances in supportive care justify the expectation that the outcomes of AML patients can be finally improved in the near future.

The focus of this Special Issue is to highlight these new advances in the treatment of AML.

Dr. Sébastien Anguille
Dr. Roland B. Walter
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 papers will be 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. Journal of Clinical Medicine is an international peer-reviewed open access monthly 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 2000 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 myeloid leukemia
  • targeted therapies
  • immunotherapy
  • vaccines
  • monoclonal antibodies
  • gene-modified T cells

Published Papers (5 papers)

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Research

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Open AccessArticle
A Mortality Prediction Rule for Hematology Patients with Invasive Aspergillosis Based on Serum Galactomannan Kinetics
J. Clin. Med. 2020, 9(2), 610; https://doi.org/10.3390/jcm9020610 - 24 Feb 2020
Abstract
In invasive aspergillosis (IA), an early and adequate assessment of the response to the initial antifungal therapy remains problematic. We retrospectively analyzed 206 hematology patients with proven or probable IA, and collected serial serum galactomannan (sGM) values and survival status through week 6 [...] Read more.
In invasive aspergillosis (IA), an early and adequate assessment of the response to the initial antifungal therapy remains problematic. We retrospectively analyzed 206 hematology patients with proven or probable IA, and collected serial serum galactomannan (sGM) values and survival status through week 6 and week 12. We created a model for survival at week 6 based on the sGM taken at baseline and on early sGM kinetics. This resulted in a rule predicting that patients with a baseline sGM index >1.4, who failed to lower that index to <0.5 after one week, had a mortality rate of 48.1% at week 6. Conversely, patients presenting with a baseline sGM index ≤1.4 that obtained a negative sGM (<0.5) after one week, had a mortality that was almost five times lower at only 10.1% by week 6. These findings were confirmed in an external cohort from an independent prospective study. In conclusion, sGM kinetics correlate well with treatment outcomes in hematology patients with IA. We present a rule which is easy to use at the bedside and has good accuracy in predicting week 6 survival. Full article
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
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Open AccessArticle
Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia
J. Clin. Med. 2020, 9(2), 536; https://doi.org/10.3390/jcm9020536 - 16 Feb 2020
Abstract
Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving [...] Read more.
Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (p = 0.027). Event-free survival was significantly different in favor of HAM-pegA (p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M. Full article
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
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Open AccessArticle
Highly Sensitive Detection of IDH2 Mutations in Acute Myeloid Leukemia
J. Clin. Med. 2020, 9(1), 271; https://doi.org/10.3390/jcm9010271 - 19 Jan 2020
Abstract
Background: Acute myeloid leukemia is a heterogeneous hematological disease, characterized by karyotypic and molecular alterations. Mutations in IDH2 have a role in diagnosis and as a minimal residue disease marker. Often the variant allele frequency during follow up is less than 20%, which [...] Read more.
Background: Acute myeloid leukemia is a heterogeneous hematological disease, characterized by karyotypic and molecular alterations. Mutations in IDH2 have a role in diagnosis and as a minimal residue disease marker. Often the variant allele frequency during follow up is less than 20%, which represents the limit of detection of Sanger sequencing. Therefore, the development of sensitive methodologies to identify IDH2 mutations might help to monitor patients’ response to therapy. We compared three different methods to identify and monitor IDH2 mutations in patients’ specimens. Methods: Performances of PNA-PCR clamping, droplet digital PCR and Sanger for IDH2 status identification were evaluated and compared in 96 DNA patients’ specimens. Results: In contrast with Sanger sequencing, our results highlighted the concordance between PNA clamping and digital PCR. Furthermore, PNA-PCR clamping was able to detect more mutated DNA with respect to Sanger sequencing that showed several false negatives independently from the allelic frequency. Conclusions: We found that PNA-PCR clamping and digital PCR identified IDH2 mutations in DNA samples with comparable results in a percentage significantly higher compared to Sanger sequencing. PNA-PCR clamping can be used even in laboratories not equipped for sophisticated analyses, decreasing cost and time for IDH2 characterization. Full article
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
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Review

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Open AccessReview
Landscape of Tumor Suppressor Mutations in Acute Myeloid Leukemia
J. Clin. Med. 2020, 9(3), 802; https://doi.org/10.3390/jcm9030802 - 16 Mar 2020
Abstract
Acute myeloid leukemia is mainly characterized by a complex and dynamic genomic instability. Next-generation sequencing has significantly improved the ability of diagnostic research to molecularly characterize and stratify patients. This detailed outcome allowed the discovery of new therapeutic targets and predictive biomarkers, which [...] Read more.
Acute myeloid leukemia is mainly characterized by a complex and dynamic genomic instability. Next-generation sequencing has significantly improved the ability of diagnostic research to molecularly characterize and stratify patients. This detailed outcome allowed the discovery of new therapeutic targets and predictive biomarkers, which led to develop novel compounds (e.g., IDH 1 and 2 inhibitors), nowadays commonly used for the treatment of adult relapsed or refractory AML. In this review we summarize the most relevant mutations affecting tumor suppressor genes that contribute to the onset and progression of AML pathology. Epigenetic modifications (TET2, IDH1 and IDH2, DNMT3A, ASXL1, WT1, EZH2), DNA repair dysregulation (TP53, NPM1), cell cycle inhibition and deficiency in differentiation (NPM1, CEBPA, TP53 and GATA2) as a consequence of somatic mutations come out as key elements in acute myeloid leukemia and may contribute to relapse and resistance to therapies. Moreover, spliceosomal machinery mutations identified in the last years, even if in a small cohort of acute myeloid leukemia patients, suggested a new opportunity to exploit therapeutically. Targeting these cellular markers will be the main challenge in the near future in an attempt to eradicate leukemia stem cells. Full article
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
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Open AccessReview
Is Hematopoietic Stem Cell Transplantation Required to Unleash the Full Potential of Immunotherapy in Acute Myeloid Leukemia?
J. Clin. Med. 2020, 9(2), 554; https://doi.org/10.3390/jcm9020554 - 18 Feb 2020
Abstract
From monoclonal antibodies (mAbs) to Chimeric Antigen Receptor (CAR) T cells, immunotherapies have enhanced the efficacy of treatments against B cell malignancies. The same has not been true for Acute Myeloid Leukemia (AML). Hematologic toxicity has limited the potential of modern immunotherapies for [...] Read more.
From monoclonal antibodies (mAbs) to Chimeric Antigen Receptor (CAR) T cells, immunotherapies have enhanced the efficacy of treatments against B cell malignancies. The same has not been true for Acute Myeloid Leukemia (AML). Hematologic toxicity has limited the potential of modern immunotherapies for AML at preclinical and clinical levels. Gemtuzumab Ozogamicin has demonstrated hematologic toxicity, but the challenge of preserving normal hematopoiesis has become more apparent with the development of increasingly potent immunotherapies. To date, no single surface molecule has been identified that is able to differentiate AML from Hematopoietic Stem and Progenitor Cells (HSPC). Attempts have been made to spare hematopoiesis by targeting molecules expressed only on later myeloid progenitors as well as AML or using toxins that selectively kill AML over HSPC. Other strategies include targeting aberrantly expressed lymphoid molecules or only targeting monocyte-associated proteins in AML with monocytic differentiation. Recently, some groups have accepted that stem cell transplantation is required to access potent AML immunotherapy and envision it as a rescue to avoid severe hematologic toxicity. Whether it will ever be possible to differentiate AML from HSPC using surface molecules is unclear. Unless true specific AML surface targets are discovered, stem cell transplantation could be required to harness the true potential of immunotherapy in AML. Full article
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
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