Clinically defining and managing high-risk pediatric patients with acute lymphoblastic leukemia

Abstract

For children with acute lymphoblastic leukemia, the identification of those at higher risk of disease recurrence and modifying therapy based on this risk is a critical component to the provision of optimal care. The specific definitions of high-risk ALL vary across cooperative groups, but the themes are consistent, being largely based on leukemia biology and disease response. Intensification of conventional chemotherapy for those with high-risk disease has led to improved outcomes. It is anticipated that the development of rational targeted therapy for specific biologically unique subsets of children with leukemia will contribute to ongoing progress in improving the outcomes for children with acute lymphoblastic anemia. Learning Objectives• To understand current criteria used to identify children with high-risk ALL • To understand therapeutic strategies for children with highrisk ALL

Establishment and characterization of a novel childhood acute lymphoblastic leukemia cell line, HXEX-ALL1, with chromosome 9p and 17p deletions

“…The list of genetic alterations in childhood ALL that are associated with the risk of relapse continues to grow. Ph chromosome, BCR - ABL1 like with IZKF1 and JAK2 alterations, MLL rearrangements, hypodiploidy (< 44 chromosomes or DNA index < 0.81), and iAMP are assigned as unfavorable characteristics [24]. In contrast, hyperdiploidy with trisomy 4 and 10 and ETV6 - RUNX1 fusion are designated favorable genetic factors [24].…”

“…Ph chromosome, BCR - ABL1 like with IZKF1 and JAK2 alterations, MLL rearrangements, hypodiploidy (< 44 chromosomes or DNA index < 0.81), and iAMP are assigned as unfavorable characteristics [24]. In contrast, hyperdiploidy with trisomy 4 and 10 and ETV6 - RUNX1 fusion are designated favorable genetic factors [24]. The results of G-banding analysis in the patient showed that the primary leukemia cells had 3 gross structural chromosomal abnormalities, namely, trisomy 8, and 9p and 17p deletions, but no unfavorable characteristics at diagnosis.…”

Examining treatment responses of diagnostic marrow in murine xenografts to predict relapse in children with acute lymphoblastic leukaemia

“… 3 – 5 This classification informs the selection of an appropriate treatment strategy, whereby those stratified into the SR and MR subtypes are treated with less intensive chemotherapy, while more aggressive protocols are reserved for those exhibiting an HR subtype. 6 – 8 …”