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Diagnosis, Management and Prognosis of Acute Leukemia (AML and ALL): Current Challenges and Opportunities

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

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 14517

Special Issue Editor

Dr. Anna Candoni

E-Mail Website
Guest Editor
Division of Hematology and Stem Cell Transplantation, University of Udine and ASUFC, Udine, Italy
Interests: acute leukemias; myelodysplastic syndromes; minimal residual diseases; infections in hematologic patients; allogeneic stem cell transplantation

Special Issue Information

Dear Colleagues,

The therapeutic field of acute leukemia is undergoing a rapid change in both young and elderly patients for whom there are many new drugs available (including specific target therapies, monoclonal antibodies, liposomal delivery formulations). In this context, precise biological study of leukemic cells and assessment and follow-up of minimal residual disease remain essential to integrate these news drugs into clinical practice and achieve the optimal treatment of leukemia. In this Special Issue, we discuss the biggest challenges and opportunities that exist today at the clinical and biological level for adult patients with acute leukemia, including genetic and prognostic classification, measurable residual disease, intensive and nonintensive therapies, consolidation and maintenance options.

Dr. Anna Candoni
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

  • acute leukemia (myeloid and lymphoid)
  • prognostic markers
  • new target therapies
  • minimal residual disease
  • stem cell transplantation
  • immunotherapy
  • quality of life

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Published Papers (4 papers)

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Research

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11 pages, 575 KiB  
Article
In BCR-ABL1 Positive B-Cell Acute Lymphoblastic Leukemia, Steroid Therapy Induces Hypofibrinogenemia
by Elisa Buzzatti, Fabio Forghieri, Giovangiacinto Paterno, Francesco Marchesi, Chiara Sarlo, Fabio Giglio, Nicola Fracchiolla, Mariarita Sciumè, Raffaele Palmieri, Fabiana Esposito, Luca Guarnera, Lisa Mercante, Maria Rosaria Pascale, Flavia Mallegni, Arianna Savi, Vittorio Forte, Luca Maurillo, Francesco Buccisano, Adriano Venditti and Maria Ilaria Del Principe
J. Clin. Med. 2022, 11(7), 1776; https://doi.org/10.3390/jcm11071776 - 23 Mar 2022
Cited by 1 | Viewed by 2250
Abstract
Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels [...] Read more.
Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels of FBG during induction treatment and explore if the FBG fall correlated with therapies other than asparaginase and/or specific leukemia biological features. We retrospectively analyzed FBG levels in 115 patients with B-ALL. In 74 (64%) out of 115 patients FBG decline occurred during the steroid prephase. In univariate analysis, such a steroid-related HF was significantly associated with BCR-ABL1 rearrangement (p = 0.00158). None of those experiencing HF had significant modifications of liver function tests during induction treatment. Our retrospective study suggests that in B-ALL, steroid therapy can also induce HF and that such an event is preferentially observed in patients carrying BCR-ABL1 rearrangements. The pathogenesis of this phenomenon is still unclear. We attempt to explain it by applying the International Society of Thrombosis and Hemostasis-Disseminated Intravascular Coagulation score (ISTH-DIC score); nonetheless additional studies are needed to clarify further the mechanisms of HF in this subset of patients. Full article
(This article belongs to the Special Issue Diagnosis, Management and Prognosis of Acute Leukemia (AML and ALL): Current Challenges and Opportunities)
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14 pages, 933 KiB  
Article
BSG (CD147) Serum Level and Genetic Variants Are Associated with Overall Survival in Acute Myeloid Leukaemia
by Piotr Łacina, Aleksandra Butrym, Eliza Turlej, Martyna Stachowicz-Suhs, Joanna Wietrzyk, Grzegorz Mazur and Katarzyna Bogunia-Kubik
J. Clin. Med. 2022, 11(2), 332; https://doi.org/10.3390/jcm11020332 - 10 Jan 2022
Cited by 11 | Viewed by 2357
Abstract
Basigin (BSG, CD147) is a multifunctional protein involved in cancer cell survival, mostly by controlling lactate transport through its interaction with monocarboxylate transporters (MCTs) such as MCT1. Previous studies have found that single nucleotide polymorphisms (SNPs) in the gene coding for BSG and [...] Read more.
Basigin (BSG, CD147) is a multifunctional protein involved in cancer cell survival, mostly by controlling lactate transport through its interaction with monocarboxylate transporters (MCTs) such as MCT1. Previous studies have found that single nucleotide polymorphisms (SNPs) in the gene coding for BSG and MCT1, as well as levels of the soluble form of BSG (sBSG), are potential biomarkers in various diseases. The goal of this study was to confirm BSG and MCT1 RNA overexpression in AML cell lines, as well as to analyse soluble BSG levels and selected BSG/MCT1 genetic variants as potential biomarkers in AML patients. We found that BSG and MCT1 were overexpressed in most AML cell lines. Soluble BSG was increased in AML patients compared to healthy controls, and correlated with various clinical parameters. High soluble BSG was associated with worse overall survival, higher bone marrow blast percentage, and higher white blood cell count. BSG SNPs rs4919859 and rs4682, as well as MCT1 SNP rs1049434, were also associated with overall survival of AML patients. In conclusion, this study confirms the importance of BSG/MCT1 in AML, and suggests that soluble BSG and BSG/MCT1 genetic variants may act as potential AML biomarkers. Full article
(This article belongs to the Special Issue Diagnosis, Management and Prognosis of Acute Leukemia (AML and ALL): Current Challenges and Opportunities)
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Review

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11 pages, 436 KiB  
Review
The Role of Wilms’ Tumor Gene (WT1) Expression as a Marker of Minimal Residual Disease in Acute Myeloid Leukemia
by Davide Lazzarotto and Anna Candoni
J. Clin. Med. 2022, 11(12), 3306; https://doi.org/10.3390/jcm11123306 - 9 Jun 2022
Cited by 13 | Viewed by 2978
Abstract
The Minimal Residual Disease(MRD) monitoring in acute myeloid leukemia (AML) is crucial to guide treatment after morphologic complete remission, to define the need for consolidation with allogeneic stem cell transplantation (Allo-SCT), and to detect impending relapse allowing early intervention. However, more than 50% [...] Read more.
The Minimal Residual Disease(MRD) monitoring in acute myeloid leukemia (AML) is crucial to guide treatment after morphologic complete remission, to define the need for consolidation with allogeneic stem cell transplantation (Allo-SCT), and to detect impending relapse allowing early intervention. However, more than 50% of patients with AML lack a specific or measurable molecular marker to monitor MRD. We reviewed the key studies on WT1 overexpression as a marker of MRD in AML patients undergoing an intensive chemotherapy program, including Allo-SCT. In addition, we provided some practical considerations on how to properly use WT1 expression as an MRD marker, considering its strengths and weaknesses. In order to achieve the best sensitivity and specificity, it is recommended to refer to the standardized method of European LeukemiaNet and its defined threshold (250 WT1 copies/104 Abelson (ABL) on Bone Marrow-BM and 50 WT1 copies/104 ABL on Peripheral Blood-PB), which has been validated in a large and multicenter cohort of patients and normal controls. Full article
(This article belongs to the Special Issue Diagnosis, Management and Prognosis of Acute Leukemia (AML and ALL): Current Challenges and Opportunities)
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13 pages, 5148 KiB  
Review
Revealing the Mysteries of Acute Myeloid Leukemia: From Quantitative PCR through Next-Generation Sequencing and Systemic Metabolomic Profiling
by Cristina Panuzzo, Aleksandar Jovanovski, Muhammad Shahzad Ali, Daniela Cilloni and Barbara Pergolizzi
J. Clin. Med. 2022, 11(3), 483; https://doi.org/10.3390/jcm11030483 - 18 Jan 2022
Cited by 12 | Viewed by 6157
Abstract
The efforts made in the last decade regarding the molecular landscape of acute myeloid leukemia (AML) have created the possibility of obtaining patients’ personalized treatment. Indeed, the improvement of accurate diagnosis and precise assessment of minimal residual disease (MRD) increased the number of [...] Read more.
The efforts made in the last decade regarding the molecular landscape of acute myeloid leukemia (AML) have created the possibility of obtaining patients’ personalized treatment. Indeed, the improvement of accurate diagnosis and precise assessment of minimal residual disease (MRD) increased the number of new markers suitable for novel and targeted therapies. This progress was obtained thanks to the development of molecular techniques starting with real-time quantitative PCR (Rt-qPCR) passing through digital droplet PCR (ddPCR) and next-generation sequencing (NGS) up to the new attractive metabolomic approach. The objective of this surge in technological advances is a better delineation of AML clonal heterogeneity, monitoring patients without disease-specific mutation and designing customized post-remission strategies based on MRD assessment. In this context, metabolomics, which pertains to overall small molecules profiling, emerged as relevant access for risk stratification and targeted therapies improvement. In this review, we performed a detailed overview of the most popular modern methods used in hematological laboratories, pointing out their vital importance for MRD monitoring in order to improve overall survival, early detection of possible relapses and treatment efficacy. Full article
(This article belongs to the Special Issue Diagnosis, Management and Prognosis of Acute Leukemia (AML and ALL): Current Challenges and Opportunities)
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