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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: closed (10 February 2025) | Viewed by 7855

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

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Published Papers (3 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
Cited by 2 | Viewed by 1776
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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37 pages, 2498 KiB  
Review
Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia
by Clifford M. Csizmar, Mark R. Litzow and Antoine N. Saliba
Cancers 2025, 17(5), 779; https://doi.org/10.3390/cancers17050779 - 25 Feb 2025
Viewed by 1433
Abstract
Despite notable progress in managing B-cell acute lymphoblastic leukemia (B-ALL) over recent decades, particularly in pediatric cohorts where the 5-year overall survival (OS) reaches 90%, outcomes for the 10–15% with relapsed and refractory disease remain unfavorable. This disparity is further accentuated in adults, [...] Read more.
Despite notable progress in managing B-cell acute lymphoblastic leukemia (B-ALL) over recent decades, particularly in pediatric cohorts where the 5-year overall survival (OS) reaches 90%, outcomes for the 10–15% with relapsed and refractory disease remain unfavorable. This disparity is further accentuated in adults, where individuals over the age of 40 years undergoing aggressive multiagent chemotherapy continue to have lower survival rates. While the adoption of pediatric-inspired treatment protocols has enhanced complete remission (CR) rates among younger adults, 20–30% of these patients experience relapse, resulting in a subsequent 5-year OS rate of 40–50%. For relapsed B-ALL in adults, there is no universally accepted standard salvage therapy, and the median OS is short. The cornerstone of B-ALL treatment continues to be the utilization of combined cytotoxic chemotherapy regimens to maximize early and durable disease control. In this manuscript, we go beyond the multiagent chemotherapy medications developed prior to the 1980s and focus on the incorporation of antibody-based therapy for B-ALL with an eye on existing and upcoming approved indications for blinatumomab, inotuzumab ozogamicin, other monoclonal antibodies, and chimeric antigen receptor (CAR) T cell products in frontline and relapsed/refractory settings. In addition, we discuss emerging investigational therapies that harness the therapeutic vulnerabilities of the disease through targeting apoptosis, modifying epigenetics, and inhibiting the mTOR pathway. Full article
(This article belongs to the Special Issue Drug Development for Acute Lymphoblastic Leukemia)
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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
Cited by 3 | Viewed by 3956
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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