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Childhood B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by recurrent genetic abnormalities that drive risk-directed treatment strategies. Using current techniques, accurate detection of such aberrations can be challenging, due to the rapidly expanding list of key genetic abnormalities. Whole genome sequencing (WGS) has the potential to improve genetic testing, but requires comprehensive validation. We performed WGS on 210 childhood B-ALL samples annotated with clinical and genetic data. We devised a molecular classification system to subtype these patients based on identification of key genetic changes in tumour-normal and tumour-only analyses. This approach detected 294 subtype-defining genetic abnormalities in 96% (202/210) patients. Novel genetic variants, including fusions involving genes in the MAP kinase pathway, were identified. WGS results were concordant with standard-of-care methods and whole transcriptome sequencing (WTS). We expanded the catalogue of genetic profiles that reliably classify PAX5alt and ETV6::RUNX1-like subtypes. Our novel bioinformatic pipeline improved detection of DUX4 rearrangements (DUX4-r): a good-risk B-ALL subtype with high survival rates. Overall, we have validated that WGS provides a standalone, reliable genetic test to detect all subtype-defining genetic abnormalities in B-ALL, accurately classifying patients for the risk-directed treatment stratification, while simultaneously performing as a research tool to identify novel disease biomarkers.

Incorporating genetics into risk-stratification for treatment of childhood B-progenitor acute lymphoblastic leukaemia (B-ALL) has contributed significantly to improved survival. In about 30% B-ALL (B-other-ALL) without well-established chromosomal changes, new genetic subtypes have recently emerged, yet their true prognostic relevance largely remains unclear. We integrated next generation sequencing (NGS): whole genome sequencing (WGS) (n = 157) and bespoke targeted NGS (t-NGS) (n = 175) (overlap n = 36), with existing genetic annotation in a representative cohort of 351 B-other-ALL patients from the childhood ALL trail, UKALL2003. PAX5alt was most frequently observed (n = 91), whereas PAX5 P80R mutations (n = 11) defined a distinct PAX5 subtype. DUX4-r subtype (n = 80) was defined by DUX4 rearrangements and/or ERG deletions. These patients had a low relapse rate and excellent survival. ETV6::RUNX1-like subtype (n = 21) was characterised by multiple abnormalities of ETV6 and IKZF1, with no reported relapses or deaths, indicating their excellent prognosis in this trial. An inferior outcome for patients with ABL-class fusions (n = 25) was confirmed. Integration of NGS into genomic profiling of B-other-ALL within a single childhood ALL trial, UKALL2003, has shown the added clinical value of NGS-based approaches, through improved accuracy in detection and classification into the range of risk stratifying genetic subtypes, while validating their prognostic significance.

Incorporating genetics into risk-stratification for treatment of childhood B-progenitor acute lymphoblastic leukaemia (B-ALL) has contributed significantly to improved survival. In about 30% B-ALL (B-other-ALL) without well-established chromosomal changes, new genetic subtypes have recently emerged, yet their true prognostic relevance largely remains unclear. We integrated next generation sequencing (NGS): whole genome sequencing (WGS) (n = 157) and bespoke targeted NGS (t-NGS) (n = 175) (overlap n = 36), with existing genetic annotation in a representative cohort of 351 B-other-ALL patients from the childhood ALL trail, UKALL2003. PAX5alt was most frequently observed (n = 91), whereas PAX5 P80R mutations (n = 11) defined a distinct PAX5 subtype. DUX4-r subtype (n = 80) was defined by DUX4 rearrangements and/or ERG deletions. These patients had a low relapse rate and excellent survival. ETV6::RUNX1-like subtype (n = 21) was characterised by multiple abnormalities of ETV6 and IKZF1, with no reported relapses or deaths, indicating their excellent prognosis in this trial. An inferior outcome for patients with ABL-class fusions (n = 25) was confirmed. Integration of NGS into genomic profiling of B-other-ALL within a single childhood ALL trial, UKALL2003, has shown the added clinical value of NGS-based approaches, through improved accuracy in detection and classification into the range of risk stratifying genetic subtypes, while validating their prognostic significance.

Introduction NICE Evidence 2019 and the RCPCH shows that the needs of young patients are complex and are rarely met comprehensively on adult wards. Young patients are often overlooked (Viner, 2007) and they are at risk of many issues that can have significant effects on their health and wellbeing. Although it is recognised that adolescents do better on adolescent wards than paediatric wards, few studies are aimed at improving their experience on the former. Methods Patients aged 17-22 were interviewed over two rounds of interviews, each consisting of 4 weeks. Interviews were carried out one-on-one using a semi-structured questionnaire. Interviews in both rounds were analysed thematically, with those in round 2 further audio recorded and transcribed for further analysis. Results 30 patients were interviewed in total, 14 in the first round and 16 in the second. Key themes included: interactions with patients and healthcare professionals, privacy, age, autonomy, and signposting issues. Suggestions for improvements included facilities such as a designated adolescent common room, computers, reading material and television; as well as emotional support via day-today visits, proper signposting and interactive tasks. Discussion A wide range of experiences both positive and negative were revealed with regards to adolescent care. Adolescent needs were shown to be even more extensive than previously realised, and work is needed to improve how they are met. The findings of this study provide valuable guidance to the improvement of adolescent care at the teaching hospital in which this study was conducted; as well as setting up a structure for similar investigations in other healthcare settings. An adolescent outreach team comprised of volunteers and led by a youth worker could make a vital difference in the provision of emotional support, as well as continuing to gain insight into what improvements most effectively benefit adolescents on adult wards.

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BACKGROUND Oncology is lacking in many medical curricula. Mentoring schemes can expose participants to specific areas of medicine and may address the shortfalls in oncology education. OBJECTIVE This study identifies motivations for participation in an oncology mentoring scheme and its benefits and limitations to mentors and mentees. METHODS The British Oncology Network for Undergraduate Societies (BONUS) launched a national oncology mentorship scheme (NOMS). Mentees (medical student or foundation doctor) were paired with mentors (speciality registrar or consultant), for six months of mentoring. Mentees and mentors were invited to complete a pre-scheme and post-scheme questionnaire. RESULTS For mentees, networking was the primary reason for joining the scheme (38%). Knowledge in all areas of oncology assessed significantly increased during the scheme (p<0.001). Most mentees (91%) and mentors (72%) felt they had benefited from the scheme. Mentees cited gaining insights into oncology, and mentors, opportunities to develop professionally as most beneficial. Whilst mentees did not report any barriers to participating in the scheme, mentors stated lack of time as the greatest barrier to mentoring. CONCLUSIONS BONUS’ NOMS is expanding and is beneficial for mentees through increasing knowledge, providing exposure, and careers advice in oncology. Mentors benefit from improving their mentoring skills and personal satisfaction.