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Targeted Treatment and Immunotherapy in High-risk and Relapsed/Refractory Pediatric Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia is the most frequent pediatric malignancy in children, comprising 30% of all pediatric malignancies; adult ALL comprises 5% of all ALL cases, which have a 186.6 per 1 million incidence. In pediatric ALL (pALL), on which this review focuses, approximately 1 in 285 childre...

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Detalles Bibliográficos
Autores principales: Graiqevci-Uka, Violeta, Behluli, Emir, Spahiu, Lidvana, Liehr, Thomas, Temaj, Gazmend
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009894/
https://www.ncbi.nlm.nih.gov/pubmed/36056858
http://dx.doi.org/10.2174/1573396318666220901165247
Descripción
Sumario:Acute lymphoblastic leukemia is the most frequent pediatric malignancy in children, comprising 30% of all pediatric malignancies; adult ALL comprises 5% of all ALL cases, which have a 186.6 per 1 million incidence. In pediatric ALL (pALL), on which this review focuses, approximately 1 in 285 children are diagnosed with cancer before the age of 20, and approximately 1 in 530 young adults between the ages of 20 and 39 years old is a childhood cancer survivor. The survival probability in pALL is now very high, approximately 80-90%. Thus, the most important is to improve supportive care and treatment based on relapse risk, optimally being based on the genetic feature of malignant cells. Improvements made by now are mainly the classifying of subgroups based on genetic characteristics such as aneuploidy or translocation and aligning them with treatment response. Relevant genetic changes in ALL pathogenesis are transcription regulators of lymphoid development (PAX5, IKZF1, EBF1, and LEF1) and/or coactivators (TBL1XR1 and ERG), lymphoid signaling (BTLA, and CD200 TOX), and tumor suppressor genes (CDKN2A, CDKN2B, RB1, and TP53). This review aims to summarize treatment strategies inhibiting tyrosine kinases, influencing different signaling pathways, BCL inhibitors, and anti-CD therapy (anti-cluster differentiation therapy) in pALL. CAR T-cell therapy (chimeric antigen receptors T-cell therapy) is under research and requires further development.