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

Abstract

Abstract: 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, ap-proximately 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 genet-ic 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 treat-ment response. Relevant genetic changes in ALL pathogenesis are transcription regulators of lym-phoid 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, in-fluencing different signaling pathways, BCL inhibitors, and anti-CD therapy (anti-cluster differenti-ation therapy) in pALL. CAR T-cell therapy (chimeric antigen receptors T-cell therapy) is under re-search and requires further development.