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Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management

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

Deadline for manuscript submissions: 31 August 2024 | Viewed by 7948

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Special Issue Editor

Dr. Michael D. Diamantidis

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Guest Editor

Thalassemia and Sickle Cell Disease Unit, Department of Hematology, General Hospital of Larissa, 41221 Larissa, Greece
Interests: acute myeloid leukemia; myelodysplastic syndromes; myeloid malignancies; myeloproliferative neoplasms; hemoglobinopathies

Special Issue Information

Dear Colleagues,

Amazing progress has been achieved in recent years regarding the better understanding of the genetic landscape of acute myeloid leukemia (AML) with the improvement of molecular diagnostics. This has led to novel classifications of the disease (ICC/ELN 2022 and WHO 2022), prognostic systems proposed by several scientific groups incorporating the genomic data of large series of AML patients with the contribution of bioinformatics and most importantly, to the approval of novel agents for the treatment of AML. Nevertheless, there is an unmet need for solving novel challenges that have emerged.

The aim of this Special Issue is to reflect the core problems and the research regarding all aspects of AML: genetic landscape of the disease, diagnostics, novel treatments, hematopoietic stem cell transplantation and cellular therapies. The manuscripts submitted can be either original papers, reviews or even remarkable cases accompanied by a literature review. The basic biology of AML, novel advances regarding clonal evolution and leukemic stem cells, novel markers for diagnosis and prognosis of AML, comparison between ICC/ELN 2022 and WHO 2022 AML classifications, risk adapted therapy, novel targeted therapies, the role of measurable residual disease (MRD) in AML, current acute promyelocytic leukemia (APL) therapeutic strategies, immunotherapy of AML, CAR-T cells and AML are of interest for this Special Issue.

We thank you and we are looking forward to receiving your work.

Dr. Michael D. Diamantidis
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. Journal of Clinical Medicine 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 2600 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

ELN
ICC and WHO 2022 AML classifications
molecular AML diagnostics
AML biology
measurable residual disease (MRD)
novel targeted AML therapies
AML immunotherapies
hematopoietic stem cell transplantation (HSCT)

Published Papers (7 papers)

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Research

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11 pages, 1361 KiB

Open AccessArticle

Differential Expression of LMNA/C and Insulin Receptor Transcript Variants in Peripheral Blood Mononuclear Cells of Leukemia Patients

by Khalid Saud Alshaalan, Turki Khalid Albawardi, Mahmoud Zhra, Norah Bin Sulaiman, Osama Yaheia Jnied, Rimah Abdullah Saleem and Ahmad Aljada

J. Clin. Med. 2024, 13(9), 2568; https://doi.org/10.3390/jcm13092568 - 27 Apr 2024

Viewed by 366

Abstract

Background: Recent research has identified alternative transcript variants of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) and insulin receptors (INSRs) as potential biomarkers for various types of cancer. The objective of this study was to assess the expression of LMNA/C and INSR transcript variants in peripheral blood mononuclear cells (PBMCs) of leukemia patients to investigate their potential as diagnostic biomarkers. Methods: Quantitative TaqMan reverse transcriptase polymerase chain reaction (RT-qPCR) was utilized to quantify the mRNA levels of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) as well as INSR (IR-A and IR-B) variants in PBMCs obtained from healthy individuals (n = 32) and patients diagnosed with primary leukemias (acute myeloid leukemia (AML): n = 17; acute lymphoblastic leukemia (ALL): n = 8; chronic myeloid leukemia (CML): n = 5; and chronic lymphocytic leukemia (CLL): n = 15). Results: Only LMNA and LMNC transcripts were notably present in PBMCs. Both exhibited significantly decreased expression levels in leukemia patients compared to the healthy control group. Particularly, the LMNC:LMNA ratio was notably higher in AML patients. Interestingly, IR-B expression was not detectable in any of the PBMC samples, precluding the calculation of the IR-A:IR-B ratio as a diagnostic marker. Despite reduced expression across all types of leukemia, IR-A levels remained detectable, indicating its potential involvement in disease progression. Conclusions: This study highlights the distinct expression patterns of LMNA/C and INSR transcript variants in PBMCs of leukemia patients. The LMNC:LMNA ratio shows promise as a potential diagnostic indicator for AML, while further research is necessary to understand the role of IR-A in leukemia pathogenesis and its potential as a therapeutic target. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

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10 pages, 1098 KiB

Open AccessArticle

FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia—Even in the Era of New Treatment Modalities Still a Significant Player

by Saša Anžej Doma, Matjaž Sever, Gorazd Jakoš and Helena Podgornik

J. Clin. Med. 2024, 13(7), 1842; https://doi.org/10.3390/jcm13071842 - 22 Mar 2024

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Abstract

(1) Background: Relapsed/refractory (r/r) and secondary acute myeloid leukemia are highlighted by chemoresistance and poor outcomes. The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with or without idarubicin (-Ida) and to discuss novel therapies in this setting. (2) Methods: Clinical and cytogenetic data on 130 consecutive patients with r/r and secondary AML treated at our center were retrospectively analyzed. (3) Results: There were 48, 56, and 26 patients with relapsed, refractory, and secondary AML, respectively. The median age was 60 years. The overall response was achieved in 70% of patients. The median overall survival (OS) time for the whole group was 9.4 months. In total, 47% of patients proceeded to allogeneic hematopoietic stem cell transplantation (aHSCT) and these patients had significantly prolonged OS compared to the others (63 months vs. 4.2 months; p < 0.001). Among the variables, including age, FLT3 mutation status, European LeukemiaNet (ELN) 2022 classification risk, FLAG vs. FLAG-Ida, and aHSCT, a multivariate analysis revealed that only aHSCT significantly influenced overall survival. (4) Conclusions: FLAG(-Ida) chemotherapy remains an effective salvage chemotherapy for patients with r/r and secondary AML with a plan of proceeding to aHSCT. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

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13 pages, 1136 KiB

Open AccessArticle

Real-Life Multicenter Experience of Venetoclax in Combination with Hypomethylating Agents in Previously Untreated Adult Patients with Acute Myeloid Leukemia in Greece

by Theodora Chatzilygeroudi, Ismini Darmani, Natali El Gkotmi, Pinelopi Vryttia, Stavroula Douna, Anthi Bouchla, Vasiliki Labropoulou, Maria Kotsopoulou, Argiris Symeonidis, Maria Pagoni, Vasiliki Pappa and Sotirios G. Papageorgiou

J. Clin. Med. 2024, 13(2), 584; https://doi.org/10.3390/jcm13020584 - 19 Jan 2024

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Abstract

Background: The landscape of first-line treatment for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy has changed remarkably after venetoclax approval. Accumulating real-world data further apprises us with more knowledgeable use. To assess the efficacy and safety challenges in the real-life setting of the combination of hypomethylated agent (HMA) and venetoclax, we conducted a multi-center retrospective study. Methods: Forty adult AML patients treated with the combination of HMA and venetoclax as a first-line treatment after full approval (2020) were included. To confirm VIALE-A results, this group was compared to a historical cohort of 17 chemotherapy-ineligible AML patients treated with HMA monotherapy before 2020. Results: The combination of HMA-venetoclax achieved a composite complete response rate of 86.8% (p < 0.001), median overall survival, and event-free survival of 33.8 and 19.7 months, respectively, in a median follow-up of 17.8 months (p_os < 0.001, HR = 0.276, CI: 0.132–0.575, p_EFS = 0.004, HR = 0.367, CI: 0.174–0.773). High rates of neutropenia (90%) and consequent infection rates (57.5%) were noted. Only 55% of our patients received antifungal prophylaxis, as its use remains controversial, and invasive fungal infections were presented in 7.5%. Conclusions: Evidently, venetoclax-HMA yields high response rates and profound survival benefits in real life and has changed our approach to alternative chemotherapy options. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

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Review

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24 pages, 1126 KiB

Open AccessReview

Venetoclax Combination Treatment of Acute Myeloid Leukemia in Adolescents and Young Adult Patients

by Elena Chatzikalil, Kleoniki Roka, Panagiotis T. Diamantopoulos, Efthymia Rigatou, Georgia Avgerinou, Antonis Kattamis and Elena E. Solomou

J. Clin. Med. 2024, 13(7), 2046; https://doi.org/10.3390/jcm13072046 - 1 Apr 2024

Viewed by 909

Abstract

Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

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21 pages, 376 KiB

Open AccessReview

Unmet Horizons: Assessing the Challenges in the Treatment of TP53-Mutated Acute Myeloid Leukemia

by Christos Stafylidis, Dimitra Vlachopoulou, Christina-Nefeli Kontandreopoulou and Panagiotis Τ. Diamantopoulos

J. Clin. Med. 2024, 13(4), 1082; https://doi.org/10.3390/jcm13041082 - 14 Feb 2024

Viewed by 780

Abstract

Acute myeloid leukemia (AML) remains a challenging hematologic malignancy. The presence of TP53 mutations in AML poses a therapeutic challenge, considering that standard treatments face significant setbacks in achieving meaningful responses. There is a pressing need for the development of innovative treatment modalities to overcome resistance to conventional treatments attributable to the unique biology of TP53-mutated (TP53^mut) AML. This review underscores the role of TP53 mutations in AML, examines the current landscape of treatment options, and highlights novel therapeutic approaches, including targeted therapies, combination regimens, and emerging immunotherapies, as well as agents being explored in preclinical studies according to their potential to address the unique hurdles posed by TP53^mut AML. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

19 pages, 5753 KiB

Open AccessReview

Approach to Acute Myeloid Leukemia with Increased Eosinophils and Basophils

by Stavros Papadakis, Ioannis Liapis, Stefanos I. Papadhimitriou, Emmanouil Spanoudakis, Ioannis Kotsianidis and Konstantinos Liapis

J. Clin. Med. 2024, 13(3), 876; https://doi.org/10.3390/jcm13030876 - 2 Feb 2024

Viewed by 1653

Abstract

There is remarkable morphologic and genetic heterogeneity in acute myeloid leukemia (AML). In a small percentage of cases of AML, increased eosinophils and/or basophils are present in the bone marrow and sometimes in the peripheral blood. This is often a puzzling diagnostic situation but also an important finding that requires special investigation. Unique chromosomal rearrangements have been correlated with an increased number of eosinophils and basophils in AML. The identification of the underlying genetic lesion that promotes eosinophilia and basophilia can dramatically change both the prognosis and the treatment of the patient. Thus, clinicians must be vigilant in searching for the cause of eosinophilia and basophilia in patients with AML, since the different causes may lead to different treatments and survival outcomes. In this article, we examine the significance of increased eosinophils and/or basophils in the context of AML, provide guidance that simplifies the differential diagnosis, and give prognostic and therapeutic information about specific subtypes of AML associated with eosinophilia and/or basophilia. Evidence supporting personalized (molecularly targeted) therapy for these patients is also presented. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

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13 pages, 625 KiB

Open AccessReview

A Review of FLT3 Kinase Inhibitors in AML

by Cristina Negotei, Andrei Colita, Iuliana Mitu, Anca Roxana Lupu, Mihai-Emilian Lapadat, Constanta Elena Popovici, Madalina Crainicu, Oana Stanca and Nicoleta Mariana Berbec

J. Clin. Med. 2023, 12(20), 6429; https://doi.org/10.3390/jcm12206429 - 10 Oct 2023

Cited by 2 | Viewed by 2373

Abstract

Acute myeloid leukemia (AML) is a highly aggressive illness distinguished by the accumulation of abnormal hematopoietic precursors in both the bone marrow and peripheral blood. The prevalence of FLT3 gene mutations is high and escalates the probability of relapse and mortality. The survival rates for AML patients, particularly those over 65, are low. FLT3 mutation screening at diagnosis is mandatory, and FLT3 inhibitors are crucial in treating AML patients with mutations. There are two categories of FLT3 mutations: FLT3-ITD located in the juxtamembrane domain and FLT3-TKD in the tyrosine kinase domain. FLT3-ITD is the most common type, affecting nearly a quarter of patients, whereas FLT3-TKD only affects 6–8% of patients. FLT3 inhibitors are now crucial in treating AML patients with FLT3 mutations. When dealing with FLT3-mutated AML, the recommended course of treatment typically involves chemotherapy and midostaurin, followed by allogeneic hematopoietic cell transplantation (HCT) to maximize the likelihood of success. Maintenance therapy can lower the risk of relapse, and gilteritinib is a better option than salvage chemotherapy for relapsed or refractory cases. Clinical trials for new or combined therapies are the most effective approach. This review discusses treatment options for patients with FLT3-mutated AML, including induction chemotherapy and options for relapsed or refractory disease. Additional treatment options may become available as more studies are conducted based on the patient’s condition and susceptibility. Full article

(This article belongs to the Special Issue Acute Myeloid Leukemia: Latest Advances in the Diagnostics, Therapeutic Strategies and Clinical Management)

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