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Therapeutic opportunities from dissecting the pre-B leukaemia bone marrow microenvironment

Laurence Rishi S. Sébastien Cheung Kotecha Malinge BPharm (Hons) MBA PhD MB ChB (Hons) MRCPCH FRACP PhD PhD Co-Head, Leukaemia Translational Research

Beyond bone: the emerging role of osteoclasts in immune regulation, leukemia development and following myeloablative therapy

Osteoclasts are important regulators of bone remodeling, with an established role in maintaining skeletal homeostasis. The emergence of osteoimmunology has identified osteoclasts as key players in the immune system. In particular, osteoclasts can initiate bi-directional crosstalk mechanisms with hematopoietic stem cells and various immune cells, such as T cells, B cells and NK cells, to influence hematopoiesis and inflammatory response.

Blinatumomab limits humoral antibody response despite boosting the influenza vaccine schedule in children with B-ALL

Nick Rishi S. Laurence Sung Gottardo Kotecha Cheung Chiu MBChB FRACP PhD MB ChB (Hons) MRCPCH FRACP PhD BPharm (Hons) MBA PhD MBBS FRACP FRCPA PhD

Abdominal Imaging at Initial Diagnosis and Following Relapse in Children With Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy and remains one of the most common causes of cancer-related death in children and adolescents. It is characterised by the proliferation of immature lymphoid cells capable of infiltrating bone marrow, blood and extramedullary sites. Five-year overall survival rates exceed 90% with current multidrug chemotherapeutic regimens. This manuscript reviews the abdominal imaging features of leukaemic infiltration in children with ALL at the time of initial diagnosis and following relapse.

Targeted Therapy for Systemic Epstein-Barr Virus–Positive T-Cell Lymphoma of Childhood

Systemic Epstein-Barr virus-positive T-cell lymphoma of childhood (STCLC) is a rare and highly aggressive malignancy with a dismal prognosis and no standard curative treatment. This report describes the first reported case of STCLC in a White child who, after experiencing failure with intensive chemotherapy regimens, achieved a complete response following targeted immunotherapy.

Dose-dependent hepatotoxicity of hydrogen peroxide in HepG2 cells and its modulation by CYP450 induction

In vitro liver models combined with metabolomics approaches offer promising alternatives to animal testing in toxicology. In this study, we investigated concentration-dependent effects of hydrogen peroxide on the intra- and extracellular metabolome of HepG2 cells using 1H Nuclear Magnetic Resonance spectroscopy. 

Pharmacogenomics in pediatric oncology: Australian adolescent or young adult and caregiver perspectives

Preemptive pharmacogenomic (PGx) testing in pediatric oncology patients could reduce toxicity and improve efficacy of medications yet remains underutilized. Consumer identified implementation barriers have not been extensively explored nor included adolescent or young adult (AYA) patient perspectives. This study describes Australian pediatric oncology consumer perspectives on PGx testing, elucidating barriers to implementation.

Blinatumomab as bridging therapy in paediatric B-cell acute lymphoblastic leukaemia complicated by invasive fungal disease

Invasive fungal disease (IFD) remains a challenging complication of treatment for paediatric acute leukaemia. Consensus fungal treatment guidelines recommend withholding chemotherapy to facilitate immune recovery in this setting, yet prolonged delays in leukaemia therapy increase risk of relapse.

Pediatric pineoblastoma: A pooled outcome study of North American and Australian therapeutic data

Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years.

Acute Lymphoblastic Leukemia in Infants: A Distinctive, High-Risk Subtype of Childhood Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) in infants younger than 1 year of age is an aggressive, high-risk subtype of childhood ALL. Infant ALL with KMT2A-r is characteristically poorly responsive to chemotherapy and hematopoietic stem cell transplantation. New strategies, such as molecularly targeted therapies and immunotherapies, are in development and show promise in preclinical models and early phase studies.