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To determine the incidence, serotype distribution and clinical outcomes of invasive pneumococcal disease in children with acute lymphoblastic leukaemia following widespread use of pneumococcal conjugate vaccines.
B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection.
B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer. Current therapeutic regimens have improved 5-year event-free survival rates to 90%, however clinical outcomes for high-risk subgroups, such as BCR-ABL1+ B-ALL and relapsed ALL, remain poor. In addition, 16% of newly diagnosed children with ALL present with vertebral compression fractures. Moreover, 16% of children with ALL undergoing glucocorticoid therapy also experience a high incidence of vertebral fractures, indicating that bone health may be compromised by both leukemia progression and osteotoxicity of chemotherapy.
Current immunization guidelines recommend one dose of influenza vaccine for children aged ≥9 years and two doses for younger or vaccine-naïve children. However, children receiving chemotherapy have an attenuated immune response. We performed a prospective open-label study in children undergoing treatment for cancer at Perth Children's Hospital, Western Australia, to examine the safety and efficacy of a boosted influenza schedule.
ETV6::RUNX1 is one of the most common recurrent genomic abnormalities in acute lymphoblastic leukaemia (ALL) and is associated with a good prognosis. High expression of NTRK1, encoding tropomyosin receptor kinase A (TrkA), confers a poor prognosis in other malignancies and may contribute to therapy resistance in patients with ETV6::RUNX1 B-ALL.
It is now well accepted that germline or de novo genetic alterations predispose to cancer development, especially during childhood. Among them, constitutive trisomy 21, also known as Down syndrome (DS), has been shown to predispose to acute leukemia affecting both the myeloid (ML-DS) and lymphoid (DS-ALL) lineages. ML-DS is associated with a good prognosis compared to children without DS, due in part to a higher sensitivity to conventional chemotherapy.
The RNA-binding protein IGF2BP3 is an oncofetal protein overexpressed in B-acute lymphoblastic leukemia and is critical for leukemogenesis in experimental models. With cancerspecific expression, functional dispensability for normal development, and an unleveraged prooncogenic function in mRNA homeostasis, IGF2BP3 represents an excellent target.
PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach.
Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD.