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Dr Laurence Cheung is doing everything he can to end the threat of childhood leukemia. His research has the potential to change countless lives, but he also has another important job – being a dad to three beautiful children.
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.
Allogeneic hematopoietic stem cell transplant (HSCT) is a proven curative therapy for children with high-risk myeloid malignancies. Disease relapse, transplant-related mortality and graft versus host disease (GvHD) are the main causes of treatment failure and death post-transplant. The optimum pretransplant conditioning regimen is yet to be defined. There is limited data regarding the use of busulfan, fludarabine and melphalan as a myeloablative conditioning regimen in children receiving HSCT for myeloid malignancies.
Rishi S. Kotecha MB ChB (Hons) MRCPCH FRACP PhD Co-Head, Leukaemia Translational Research rishi.kotecha@health.wa.gov.au Co-Head, Leukaemia
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.
Extensive research over the past 50 years has resulted in significant improvements in survival for patients diagnosed with leukemia. Despite this, a subgroup of patients harboring high-risk genetic alterations still suffer from poor outcomes. There is a desperate need for new treatments to improve survival, yet consistent failure exists in the translation of in vitro drug development to clinical application.
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.
Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions.
Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS.