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Cancers
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Drug Development for Acute Lymphoblastic Leukemia
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Drug Development for Acute Lymphoblastic Leukemia

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

Deadline for manuscript submissions: 10 August 2024 | Viewed by 2350

Special Issue Editor

Dr. Rajesh Ramakrishnan Nair

E-Mail Website
Guest Editor
Investigational Drug Services, Moffitt Cancer Center, Tampa, FL, USA
Interests: B-cell acute lymphoblastic leukemia

Special Issue Information

Dear Colleagues,

Acute lymphoblastic leukemia (ALL) is characterized by the accumulation of premature lymphoid cells within the bone marrow, leading to the disruption of normal hematopoiesis. Diagnosis of the disease usually involves analysis of complete blood count with differential bone marrow aspiration and biopsy followed by cell assessment, phenotyping (flow cytometry), karyotyping (cytogenetics), in situ hybridization (FISH), polymerase chain reaction, and next-generation sequencing. Based on the diagnosis,  ALL can be classified as B-cell or T-cell lymphoblastic leukemia. It can be further divided into subtypes depending on genetic alterations such as chromosomal abnormality, chromosomal translocation, rearrangement, and fusion. Interestingly, the subtypes have been shown to influence patient’s prognosis and, therefore, accurate diagnosis plays a pivotal role in the selection of treatment regimens.

Acute lymphoblastic leukemia (ALL) remains a predominantly pediatric disease, with only about 40% of overall cases attributed to adults. Treatment involves induction, consolidation, and maintenance phases and involves chemotherapy, antibody-based therapy (monoclonal and bispecific T-cell-engaging), chemoimmunotherapy, cell-based therapy (CAR-T), tyrosine kinase inhibitors, and hematopoietic stem cell transplantation. Not surprisingly, the remission rate in ALL is very high but challenges, such as minimal residual disease leading to a relapse/refractory disease profile, remain. This issue will present the various facets of ALL and give an overall view of biology and treatment advancements and modalities in this field.

Dr. Rajesh Ramakrishnan Nair
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.

Published Papers (2 papers)

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Research

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16 pages, 2593 KiB  
Article
A Single Dose of PEG-Asparaginase at the Beginning of Induction Not Only Accelerates MRD Clearance but Also Improves Long-Term Outcome in Children with B-Lineage ALL
by Alexander Popov, Günter Henze, Julia Roumiantseva, Oleh Bydanov, Mikhail Belevtsev, Tatiana Verzhbitskaya, Liudmila Movchan, Grigory Tsaur, Svetlana Lagoyko, Liudmila Zharikova, Natalia Myakova, Dmitry Litvinov, Olga Khlebnikova, Olga Streneva, Elena Stolyarova, Natalia Ponomareva, Galina Novichkova, Larisa Fechina, Olga Aleinikova and Alexander Karachunskiy
Cancers 2023, 15(23), 5547; https://doi.org/10.3390/cancers15235547 - 23 Nov 2023
Viewed by 739
Abstract
This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 [...] Read more.
This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 of induction therapy in children with B-lineage ALL. Methods. Conventional induction therapy consisted of dexamethasone, vincristine, and daunorubicin. MRD data was available in 502 patients who were randomized at the start of induction therapy, standard-risk (SR) patients into three (conventional induction without PEG, induction with additional PEG and with PEG but without daunorubicin) and intermediate-risk (ImR) patients into two groups (with additional PEG and without PEG). Results. The single administration of PEG resulted in a significantly higher proportion of rapid responders, in SR patients even when no anthracyclines were used for induction. In the SR group, the event-free survival of the MFC-MRD fast responders was similar in the PEG− and PEG+ arms (92.0 ± 3.1% vs. 96.2 ± 1.5%, respectively), and the same unfavorable trend was observed for MFC-MRD slow responders (57.5 ± 12.3% vs. 66.7 ± 15.7%, respectively). Results were similar in ImR patients: (94.3 ± 3.2% vs. 95.1 ± 2.4%, for fast responders and 63.3 ± 7.6% vs. 78.1 ± 7.9%, for slow responders in PEG− and PEG+ arms, respectively). However, there is a large difference between the proportion of MFC-MRD slow responders in the PEG− and PEG+ groups (18.3% vs. 5.2% for the SR group and 44.2% vs. 25.0% for the ImR group). Conclusions. Therefore, early use of PEG-ASP not only leads to an accelerated reduction of blasts, but also to an excellent outcome in a significantly larger proportion of patients in both risk groups. Full article
(This article belongs to the Special Issue Drug Development for Acute Lymphoblastic Leukemia)
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Review

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16 pages, 902 KiB  
Review
Biological Markers of High-Risk Childhood Acute Lymphoblastic Leukemia
by Jiasen He, Faryal Munir, Samanta Catueno, Jeremy S. Connors, Amber Gibson, Lindsay Robusto, David McCall, Cesar Nunez, Michael Roth, Priti Tewari, Sofia Garces, Branko Cuglievan and Miriam B. Garcia
Cancers 2024, 16(5), 858; https://doi.org/10.3390/cancers16050858 - 21 Feb 2024
Viewed by 1243
Abstract
Childhood acute lymphoblastic leukemia (ALL) has witnessed substantial improvements in prognosis; however, a subset of patients classified as high-risk continues to face higher rates of relapse and increased mortality. While the National Cancer Institute (NCI) criteria have traditionally guided risk stratification based on [...] Read more.
Childhood acute lymphoblastic leukemia (ALL) has witnessed substantial improvements in prognosis; however, a subset of patients classified as high-risk continues to face higher rates of relapse and increased mortality. While the National Cancer Institute (NCI) criteria have traditionally guided risk stratification based on initial clinical information, recent advances highlight the pivotal role of biological markers in shaping the prognosis of childhood ALL. This review delves into the emerging understanding of high-risk childhood ALL, focusing on molecular, cytogenetic, and immunophenotypic markers. These markers not only contribute to unraveling the underlying mechanisms of the disease, but also shed light on specific clinical patterns that dictate prognosis. The paradigm shift in treatment strategies, exemplified by the success of tyrosine kinase inhibitors in Philadelphia chromosome-positive leukemia, underscores the importance of recognizing and targeting precise risk factors. Through a comprehensive exploration of high-risk childhood ALL characteristics, this review aims to enhance our comprehension of the disease, offering insights into its molecular landscape and clinical intricacies in the hope of contributing to future targeted and tailored therapies. Full article
(This article belongs to the Special Issue Drug Development for Acute Lymphoblastic Leukemia)
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