J. V. Gil
J. Ribera
M. Llop- 1Grupo de Investigación en Hematología y Hemoterapia, Instituto de Investigación Sanitaria la Fe, Valencia, Spain
- 2Acute Lymphoblastic Leukaemia Group, Josep Carreras Leukaemia Research Institute, Badalona, Spain
- 3Unidad de Biología Molecular, Hospital Universitari I Politècnic la Fe, Valencia, Spain
Editorial on the Research Topic
Pediatric acute lymphoblastic leukemia: what’s next?
Word limit consideration
Adhering to the prescribed word limit, this editorial concisely synthesizes the key themes and findings from the four contributing articles. The objective is to provide a comprehensive overview without being an exhaustive table of contents, respecting the guidelines that govern the editorial's length.
Introduction
Acute lymphoblastic leukemia (ALL) is the most common hematological cancer in children. The survival rates have improved significantly in recent decades, and the current therapy strategies focus on limiting toxicities and improving outcomes in very high risk and relapsed patients. The benefit of emerging treatments such as targeted drugs and immunotherapy (antibodies, CAR-T-cells) is being explored, and thus basic and clinical research will provide the knowledge to better understand and manage pediatric ALL. This research topic aimed to discover what's next in ALL. This hematologic malignancy has been analyzed from different points of view.
Contributing articles
A mini-review conducted by Stolpa et al. examined the prognostic role of CD34+CD38− lymphoblasts in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) at the time of diagnosis. Despite the lack of statistically significant differences in the initial treatment response, the presence of CD34+CD38− lymphoblasts is identified as a potential unfavorable prognostic factor for disease recurrence. Similar studies have investigated the prognostic impact of specific cell surface markers in leukemia (1, 2). Beyond the assessment of specific cell populations at diagnosis, research on minimal residual disease (MRD) has consistently shown its significance in predicting treatment response and long-term outcomes in ALL (3).
An original research conducted by Terra Correa et al. focused on the overall and event-free survival rates of pediatric ALL patients in a Brazilian center. The study revealed that despite advancements in treatment, the survival rates are comparable with previous studies conducted in Brazil, which are lower than those observed in developed countries. The challenges in risk stratification, prognostic testing, and the impact of treatment-related adverse effects highlight the complexities in improving outcomes for pediatric ALL. Comparative studies from different regions have reported variations in survival rates and treatment outcomes. For example, a global analysis conducted by Hunger et al. (4) emphasized the disparities in survival rates for pediatric ALL on a global scale, pointing to the need for region-specific strategies and improvements in treatment protocols to enhance survival outcomes.
Velasco et al. provided a perspective introducing the Relapsed ALL Network (ReALLNet), a pioneering initiative that connects patient care with expert groups in relapsed or refractory ALL. This network, established under the European strategic plan, aims to facilitate interdisciplinary collaboration, preclinical research, and data collection to address the unique challenges posed by this patient population. Similar initiatives, such as the Children's Oncology Group (COG) in the United States and the UKALLR3 trial in the United Kingdom, have demonstrated the efficacy of collaborative networks in conducting clinical trials, sharing data, and advancing the understanding of relapsed ALL. In the same line, molecular platforms, such as the LEAP consortium project (5) in the United States and INFORM (6) in Germany, demonstrated that between 8% and 12% of patients with a relapsed malignancy can benefit from a targeted treatment based on oncogenomic studies guided by a multidisciplinary national board. These networks play a crucial role in providing precision medicine in pediatric oncology.
Onyije et al. presented a viewpoint regarding the risk factors associated with childhood ALL, which are important for identifying modifiable factors for effective prevention. Noteworthy findings include the association between maternal exposure to pesticides and childhood ALL risk, as well as the upgraded evidence on childhood exposure to domestic radon. These updates contribute to our ongoing efforts to understand and mitigate the risk factors associated with childhood ALL. Similar findings have been reported in meta-analyses and systematic reviews. For instance, a meta-analysis conducted by Bailey et al. (7) supported the association between maternal pesticide exposure and childhood leukemia risk. In addition, studies on environmental factors, including radon exposure, have indicated their potential role in developing leukemia, contributing to the ongoing efforts to identify modifiable risk factors (8, 9).
In conclusion, the research topic “Acute Lymphoblastic Leukemia: What's Next” exemplifies the dynamic nature of ALL research, presenting findings that propel us toward a deeper understanding of the disease and its management.
Author contributions
JG: Writing – original draft, Writing – review & editing. JR: Writing – original draft, Writing – review & editing. ML: Writing – original draft, Writing – review & editing.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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References
1. Jiang Z, Wu D, Lin S, Li P. CD34 and CD38 are prognostic biomarkers for acute B lymphoblastic leukemia. Biomark Res. (2016) 4(1):1. doi: 10.1186/s40364-016-0080-5
2. Blatt K, Menzl I, Eisenwort G, Cerny-Reiterer S, Herrmann H, Herndlhofer S, et al. Phenotyping and target expression profiling of CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in acute lymphoblastic leukemia. Neoplasia. (2018) 20(6):632–42. doi: 10.1016/j.neo.2018.04.004
3. Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol. (2015) 33(27):2938–48. doi: 10.1200/jco.2014.59.1636
4. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. (2012) 30(14):1663–9. doi: 10.1200/jco.2011.37.8018
5. Walter RB, Michaelis LC, Othus M, Uy GL, Radich JP, Little RF, et al. Intergroup LEAP trial (S1612): a randomized phase 2/3 platform trial to test novel therapeutics in medically less fit older adults with acute myeloid leukemia. Am J Hematol. (2017) 93(2):49–52. doi: 10.1002/ajh.24980
6. Van Tilburg CM, Pfaff E, Pajtler KW, Langenberg KP, Fiesel P, Jones BC, et al. The pediatric precision oncology INFORM registry: clinical outcome and benefit for patients with very high-evidence targets. Cancer Discov. (2021) 11(11):2764–79. doi: 10.1158/2159-8290.cd-21-0094
7. Bailey HD, Infante-Rivard C, Metayer C, Clavel J, Lightfoot T, Kaatsch P, et al. Home pesticide exposures and risk of childhood leukemia: findings from the childhood leukemia international consortium. Int J Cancer. (2015) 137(11):2644–63. doi: 10.1002/ijc.29631
8. Kendall GM, Wakeford R, Bunch K, Vincent TJ, Little MP. Residential mobility and associated factors in relation to the assessment of exposure to naturally occurring radiation in studies of childhood cancer. J Radiol Prot. (2015) 35(4):835–68. doi: 10.1088/0952-4746/35/4/835
Keywords: acute lymphoblastic leukemia, overall survival, molecular characterization, surface markers, precision medicine
Citation: Gil JV, Ribera J and Llop M (2024) Editorial: Pediatric acute lymphoblastic leukemia: what's next?. Front. Pediatr. 11:1358139. doi: 10.3389/fped.2023.1358139
Received: 19 December 2023; Accepted: 27 December 2023;
Published: 10 January 2024.
Edited and Reviewed by: Birgit Knoechel, Dana–Farber Cancer Institute, United States
© 2024 Gil, Ribera and Llop. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: M. Llop llop_margar@gva.es