Outcomes of Paediatric Acute Promyelocytic Leukaemia in the UK

Acute Promyelocytic Leukaemia (APL) is characterized by unique genetic and molecular abnormalities, clinical features, and treatment strategies. It accounts for 5-10% of paediatric acute myeloid leukaemia (AML) cases. APL is defined by the t(15;17)(q24;q21) chromosomal translocation, leading to the formation of the PML-RARA fusion protein, which plays a crucial role in leukemogenesis. All-trans retinoic acid (ATRA) has revolutionized APL management by targeting the PML-RARA fusion protein and inducing complete remission in the majority of patients. Arsenic trioxide (ATO) has emerged as an effective therapeutic agent, particularly in cases with ATRA resistance or relapse. ATO is now widely recommended as part upfront treatment. However, access to ATO has been limited by funding sources in certain countries.

This retrospective national study presents the treatment strategies, complications, and survival outcomes of 50 paediatric patients, aged 1 to 18 years, diagnosed with APL in the UK over an 8-year period, between 1^st November 2014 and 31^st October 2021. There were 21 (42%) high risk (HR) patience and 29 (58%) non-HR patients in the cohort. The majority of patients received a chemotherapy-free regimen comprising ATRA and ATO, with additional agents used selectively. Chemotherapy was usually given to patients in the event of lack of access to ATO or clinical urgency. Availability to ATO varied between countries within the UK.

Event-free survival (EFS) and overall survival (OS) were evaluated, with a minimum 2 years follow up from diagnosis and median follow-up of 8 years. Overall, the cohort demonstrated a high OS of 94%, with no significant difference observed between HR and non-HR patients. However, HR patients experienced significantly lower EFS, with all relapses occurring in this group. Relapsed patients received varied treatment regimens, including ATRA, ATO, and chemotherapy, with favourable outcomes.

This study contributes valuable insights into the management and outcomes of paediatric APL in the UK, emphasizing the importance of early diagnosis and risk stratification for optimal treatment decisions. Addressing disparities in ATO availability and promoting consistent funding across NHS Trusts will be crucial in further improving patient outcomes and reducing relapse rates in APL. Future research should focus on refining treatment protocols and exploring novel therapeutic strategies to enhance the long-term survival of paediatric APL patients. The study highlights the challenges associated with ATO availability across NHS Trusts, impacting treatment decisions and outcomes for APL patients.