Beyond Medical Care: How Different National Models of Care Impact the Experience of Adolescent and Young Adult Cancer Patients.

Patient experience is positively associated with clinical effectiveness, quality care, and patient safety. This study examines the experience of care of adolescents and young adult (AYA) cancer patients from Australia and the United States, allowing a comparison of patient experiences in the context of different national models of cancer care delivery. Participants (n = 190) were aged 15-29 years and received cancer treatment from 2014 to 2019. Australians (n = 118) were recruited nationally by health care professionals. U.S. participants (n = 72) were recruited nationally via social media. The survey included demographic and disease variables, and questions regarding medical treatment, information and support provision, care coordination, and satisfaction across the treatment pathway. Sensitivity analyses examined the possible contribution of age and gender. Most patients from both countries were satisfied or very satisfied with their medical treatment (chemotherapy, radiotherapy, and surgery). There were significant differences between countries in the provision of fertility preservation services, age-appropriate communication, and psychosocial support. Our findings suggest when a national system of oversight with both state and federal funding is implemented, as is the case in Australia but not in the United States, significantly more AYAs with cancer receive age-appropriate information and support services, and improved access to specialist services such as fertility care. A national approach with government funding and centralized accountability appears to be associated with substantial benefits for the well-being of AYAs undergoing cancer treatment.

Safety, Feasibility and Efficacy of Lokomat® and Armeo®Spring Training in Deconditioned Paediatric, Adolescent and Young Adult Cancer Patients.

BACKGROUND: Rehabilitation robotics is a field of study which aims to understand and augment rehabilitation through the use of robotics devices. OBJECTIVE: This proof of concept study aimed to test the safety (no. adverse events, incidence of infection), feasibility (program demand, adherence, participant satisfaction) and efficacy (Peak Oxygen uptake (VO2peak), 6-min walk test, gait speeds, Canadian Occupational Performance Measure, quality of life) of Lokomat® and Armeo®Spring training in children and adolescents and young adults (AYAs) during or soon after cancer treatment. METHOD: This was a 6-week single arm pre-post study. Cancer patients with significant musculoskeletal, neurological, gait and/or upper limb deficiency aged 5 to 25 years were recruited. The rehabilitation program included access to two robotic orthoses: the Lokomat® and/or Armeo®Spring. Robotic devices utilised real-time biofeedback and computer games to engage and guide participants through a repetitive functional range of movement aimed at improving functional deficiencies. Progressive increases in exercise intensity and duration were encouraged. RESULTS: Twentey-eight participants were approached for study; twenty-one consented. Seventy-six percent completed the six-week intervention with an overall adherence of 83%. The mean participant satisfaction score was 8.8/10. Forty-nine adverse events were recorded throughout the course of the study, forty-five grade 1, three grade 2 and one grade 3. No adverse events led to withdrawal from the study. Preliminary efficacy results indicate large beneficial effects on VO2peak (r = 0.63), 10 m comfortable pace walk (r = 0.51) and maximal pace walk (r = 0.60), 6-min walk test (r = 0.60), maximal back and leg strength (r = 0.71), trunk flexibility (r = 0.60), The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) (r = 0.61), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT F) r = 0.53 and the Canadian Occupational Performance Measure, satisfaction (r = 0.88) and performance scores (r = 0.83), and moderate beneficial effects on Leisure Score Index (LSI) (r = 0.30). CONCLUSION: Our results suggest that Lokomat® and Armeo®Spring training is safe and feasible for use in children and AYAs who are currently undergoing or have recently completed cancer therapy. A larger controlled trial investigating the efficacy of robotics rehabilitation in this cohort is warranted.

Case Report: Rare IKZF1 Gene Fusions Identified in Neonate with Congenital KMT2A-Rearranged Acute Lymphoblastic Leukemia.

Chromosomal rearrangements involving the KMT2A gene occur frequently in acute lymphoblastic leukaemia (ALL). KMT2A-rearranged ALL (KMT2Ar ALL) has poor long-term survival rates and is the most common ALL subtype in infants less than 1 year of age. KMT2Ar ALL frequently occurs with additional chromosomal abnormalities including disruption of the IKZF1 gene, usually by exon deletion. Typically, KMT2Ar ALL in infants is accompanied by a limited number of cooperative le-sions. Here we report a case of aggressive infant KMT2Ar ALL harbouring additional rare IKZF1 gene fusions. Comprehensive genomic and transcriptomic analyses were performed on sequential samples. This report highlights the genomic complexity of this particular disease and describes the novel gene fusions IKZF1::TUT1 and KDM2A::IKZF1.

B-cell acute lymphoblastic leukaemia: recent discoveries in molecular pathology, their prognostic significance, and a review of the current classification.

Acute lymphoblastic leukaemia (ALL) remains a leading cause of non-traumatic death in children, and the majority of adults diagnosed will succumb to the disease. Recent advances in molecular biology and bioinformatics have enabled more detailed genomic analysis and a better understanding of the molecular biology of ALL. A number of recurrent genomic drivers have recently been described, which not only aid in diagnosis and prognostication, but also may offer opportunities for specific therapeutic targeting. The present review summarises B-ALL genomic pathology at diagnosis, including lesions detectable using traditional cytogenetic methods as well as those detected only through advanced molecular techniques.

TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets.

The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if <1000 ng/mL, imatinib 800 mg/day was given. Patients were then assessed against molecular targets: BCR-ABL1 ≤10%, ≤1%, and ≤0.1% at 3, 6, and 12 months, respectively. Cohort 1 patients failing any target escalated to imatinib 800 mg/day, and subsequently switched to nilotinib 400 mg twice daily for failing the same target 3 months later. Cohort 2 patients failing any target switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of patients remained on imatinib, and 30% on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64% at 12 months and 73% at 24 months. MR4.5 (BCR-ABL1 ≤0.0032%) at 24 months was 34%. Overall survival was 96% and transformation-free survival was 95% at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404.