Atypical hemolytic uremic syndrome (aHUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by thrombocytopenia, acute kidney injury, and microangiopathic hemolytic anemia. Our understanding of TMA is evolving, especially regarding its underlying causes. Complement dysregulation plays a pivotal role in the pathogenesis of aHUS, with up to 60% of patients harboring either complement gene variants or testing positive for anti-factor H antibodies. Additionally, non-complement-related hereditary variants, such as those in DGKE, MMACHC, and EXOSC3, can also lead to TMA phenotype. 


Secondary HUS encompasses conditions where complement activation occurs alongside other disease processes, including infections, malignant hypertension, autoimmune diseases, malignancies, transplantation, pregnancy, and certain medications. It is essential to note that this classification is not absolute; genetic variants in complement genes have been found in patients with secondary TMA, making it difficult to distinguish between complement-mediated and secondary causes of TMA. 


Accurate diagnosis of TMA necessitates specialized laboratory expertise in genetics and immunology. Treatment strategies are contingent upon the underlying cause. While plasma exchange has historically been the standard approach, patients often face high rates of kidney failure and mortality. The advent of complement inhibitors has significantly improved outcomes, yet these therapies remain costly and less accessible in low-resource settings. The optimal dosing and duration of anti-complement therapy are still under investigation. A global research initiative is essential to tackle these challenges and enhance our understanding of aHUS.

The Haematology & Oncology Centre at Hong Kong Children's Hospital has been delivering high-quality advanced therapy services for children with high-risk malignant conditions since late 2018.


Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. With improvements in standard chemotherapy and supportive care, the 5-year event-free survival rate for low-risk ALL is nearing 90%. However, treatment options have been limited for patients who experience relapse, especially early relapse, or have refractory leukemia. Advances in precision medicine have revolutionized treatment for high-risk malignancies through novel and targeted therapies. Significant progress in diagnostic and monitoring strategies, such as extensive use of genetic and molecular sequencing, along with ex-vivo chemosensitivity testing for refractory leukemia, have enhanced diagnosis accuracy, disease monitoring, and treatment selection. These advancements ultimately influence prognosis.

Paediatric brain tumours and solid tumours remain a significant challenge in oncology, with conventional treatment modalities such as chemotherapy often limited by toxicity, resistance, and a lack of specificity. These limitations have led to suboptimal survival outcomes and significant long-term side effects in children. The bottleneck of chemotherapy underscores the urgent need for innovative therapeutic approaches that can improve efficacy while reducing collateral harm.
Advances in diagnostic techniques and molecular classification have revolutionized our understanding of paediatric cancers. High-throughput sequencing and molecular profiling have enabled the identification of distinct genetic and epigenetic alterations driving individual tumours. These discoveries have paved the way for the stratification of childhood cancers into biologically defined subgroups, allowing for more accurate prognostication and tailored therapeutic strategies.
In parallel, the field of precision medicine has seen the rapid development of novel agents, including targeted therapies, immunotherapies, and small-molecule inhibitors, that address the unique molecular vulnerabilities of paediatric tumours. Agents such as tyrosine kinase inhibitors, immune checkpoint inhibitors, and cellular therapies are transforming the therapeutic landscape, offering hope for improved outcomes in diseases previously deemed refractory. However, the translation of these breakthroughs into clinical practice for children remains challenging, with hurdles including limited clinical trial data, regulatory complexities, and the unique biology of paediatric cancers compared to their adult counterparts.
There is no free lunch in precision medicine; it relies heavily on a strong multidisciplinary team to seek and deliver novel agents effectively. Hopefully, after this sharing, you will be convinced that precision medicine is not optional but mandatory for every child suffering from cancer.