Title:Targeted Treatment and Immunotherapy in High-risk and Relapsed/
Refractory Pediatric Acute Lymphoblastic Leukemia
Volume: 19
Issue: 2
Author(s): Violeta Graiqevci-Uka, Emir Behluli, Lidvana Spahiu, Thomas Liehr and Gazmend Temaj*
Affiliation:
- Faculty of Pharmacy, UBT College, Prishtina, Kosovo
Keywords:
Pediatric acute lymphoblastic leukemia (pALL), gene fusion, signaling pathway, diagnosis, treatment, CAR T-cell therapy, transcription regulators.
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, 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.
