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Cancers
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New Perspectives on Acute Myeloid Leukemia in Children
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New Perspectives on Acute Myeloid Leukemia in Children

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 4117

Special Issue Editor

Prof. Dr. Dirk Reinhardt

E-Mail Website
Guest Editor
Department of Pediatric Hematology and Oncology, Clinic of Pediatrics III, University Hospital Essen, 45147 Essen, Germany
Interests: acute myeloid leukemia; leukemogenesis; stem cell biology; gene therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the substantial improvement in survival of children with acute myeloid leukemias, there are still numerous tasks to further optimize leukemia therapy in view of the still relevant relapse rates, acute and long-term toxicities, large international disparities and deaths.

The availability of modern diagnostic and research tools (next-generation sequencing, genome mapping, single-cell analysis, in vivo models), data analysis (real-world data, machine learning, artificial intelligence), and treatment options (small molecules, immunomodulation, cellular therapies) promises new results in elucidating

This Special Issue aims to provide new insights to leukemia etiology, prognostic factors, supporting regions of inadequate care, and most importantly, developing more effective treatment options with fewer side effects.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Benefits and challenges of recent developments in molecular diagnostics
  • Leukemia stem cells, clonal evolution, and hierarchies
  • Innovative tools (machine learning/artificial intelligence) to analyze and integrate biological and clinical data
  • Prognostics markers and stratification: Relevance, combination, hierarchy
  • Targeted therapies, immunomodulation, and cellular therapies.

I look forward to receiving your contributions.

Prof. Dr. Dirk Reinhardt
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

  • acute myeloid leukemia
  • children
  • adolescents
  • next-generation sequencing
  • genome mapping
  • leukemogenesis
  • clonal evolution
  • machine learning
  • artificial intelligence
  • T-CAR
  • NK-CAR

Published Papers (3 papers)

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Research

20 pages, 2818 KiB  
Article
Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial
by Anneke D. van Dijk, Fieke W. Hoff, Yihua Qiu, Stefan E. Hubner, Robin L. Go, Vivian R. Ruvolo, Amanda R. Leonti, Robert B. Gerbing, Alan S. Gamis, Richard Aplenc, Edward A. Kolb, Todd A. Alonzo, Soheil Meshinchi, Eveline S. J. M. de Bont, Terzah M. Horton and Steven M. Kornblau
Cancers 2024, 16(8), 1448; https://doi.org/10.3390/cancers16081448 - 9 Apr 2024
Viewed by 686
Abstract
The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children’s Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin [...] Read more.
The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children’s Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and higher 3-year relapse risk after AML standard treatment compared to low expressions (52% vs. 29%, p = 0.005). The high-HME profile correlated with more transposase-accessible chromatin, as demonstrated via ATAC-sequencing, and the bortezomib addition improved the 3-year overall survival compared with standard therapy (62% vs. 75%, p = 0.033). These data suggest that there are pediatric AML populations that respond well to bortezomib-containing chemotherapy. Full article
(This article belongs to the Special Issue New Perspectives on Acute Myeloid Leukemia in Children)
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18 pages, 784 KiB  
Article
The PedAL/EuPAL Project: A Global Initiative to Address the Unmet Medical Needs of Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia
by Valeria Ceolin, Sae Ishimaru, Seth E. Karol, Francisco Bautista, Bianca Frederika Goemans, Gwenaëlle Gueguen, Marieke Willemse, Laura Di Laurenzio, Jennifer Lukin, Harm van Tinteren, Franco Locatelli, Arnaud Petit, Daisuke Tomizawa, Alice Norton, Gertjan Kaspers, Dirk Reinhardt, Sarah K. Tasian, Gwen Nichols, Edward Anders Kolb, Christian Michel Zwaan and Todd Michael Cooperadd Show full author list remove Hide full author list
Cancers 2024, 16(1), 78; https://doi.org/10.3390/cancers16010078 - 22 Dec 2023
Viewed by 1156
Abstract
The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40–50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed [...] Read more.
The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40–50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed for these children. The Pediatric Acute Leukemia (PedAL) program is a strategic global initiative that aims to overcome the obstacles in treating children with relapsed/refractory acute leukemia and is supported by the Leukemia and Lymphoma Society in collaboration with the Children’s Oncology Group, the Innovative Therapies for Children with Cancer consortium, and the European Pediatric Acute Leukemia (EuPAL) foundation, amongst others. In Europe, the study is set up as a complex clinical trial with a stratification approach to allocate patients to sub-trials of targeted inhibitors at relapse and employing harmonized response and safety definitions across sub-trials. The PedAL/EuPAL international collaboration aims to determine new standards of care for AML in a first and second relapse, using biology-based selection markers for treatment stratification, and deliver essential data to move drugs to front-line pediatric AML studies. An overview of potential treatment targets in pediatric AML, focused on drugs that are planned to be included in the PedAL/EuPAL project, is provided in this manuscript. Full article
(This article belongs to the Special Issue New Perspectives on Acute Myeloid Leukemia in Children)
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15 pages, 821 KiB  
Article
Pediatric Acute Myeloid Leukemia Post Cytotoxic Therapy—Retrospective Analysis of the Patients Treated in Poland from 2005 to 2022
by Małgorzata Czogała, Wojciech Czogała, Katarzyna Pawińska-Wąsikowska, Teofila Książek, Karolina Bukowska-Strakova, Barbara Sikorska-Fic, Paweł Łaguna, Jolanta Skalska-Sadowska, Jacek Wachowiak, Anna Rodziewicz-Konarska, Małgorzata Moj-Hackemer, Krzysztof Kałwak, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Anna Fałkowska, Katarzyna Drabko, Marta Kozłowska, Ninela Irga-Jaworska, Katarzyna Bobeff, Wojciech Młynarski, Renata Tomaszewska, Tomasz Szczepański, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Mycko, Wanda Badowska, Karolina Zielezińska, Tomasz Urasiński, Natalia Bartoszewicz, Jan Styczyński, Walentyna Balwierz and Szymon Skoczeńadd Show full author list remove Hide full author list
Cancers 2023, 15(3), 734; https://doi.org/10.3390/cancers15030734 - 25 Jan 2023
Viewed by 1772
Abstract
Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children [...] Read more.
Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7–12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015–2022 (two induction cycles followed by stem cell transplantation—SCT in 69% of patients) compared to 2005–2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 (p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 (p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015–2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML. Full article
(This article belongs to the Special Issue New Perspectives on Acute Myeloid Leukemia in Children)
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