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Title: Acute leukaemia in children, adolescents and young adults in California : trends and inequalities in early death and survival during 1988-2011
Author: Abrahao, Renata
ISNI:       0000 0004 5993 5900
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2016
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Survival after acute paediatric (0–14 years), adolescent (15–19 years) and young adult (20–39 years) leukaemia has improved substantially over the last five decades, particularly for acute lymphoblastic leukaemia (ALL) and acute promyelocytic leukaemia, a subtype of acute myeloid leukaemia. This progress represents one of the most successful achievements in the history of medicine and has been attributed to the development of effective chemotherapy regimens, improvement in supportive care, better risk stratification, use of targeted therapies, and advances in haematopoietic stem cell transplantation. Currently, long-term survival for children diagnosed with acute lymphoblastic leukaemia is 80%–90% in developed countries. Strikingly, survival among adolescents and young adults with this disease is about 60% and 40% respectively. In addition, in these countries, 5-year survival for young patients with acute myeloid leukaemia (excluding acute promyelocytic leukaemia) remains approximately 60% in the modern era of treatment. This project aimed to evaluate how survival and, when appropriate, early death (death occurring within 30 days of diagnosis) after acute leukaemia varied during almost 25 years in California, the most populous and racially/ethnically diverse state in the United States (US). A second aim was to investigate the association between sociodemographic and selected clinical factors and outcomes. Using high-quality data from the California Cancer Registry, I evaluated survival trends from acute lymphoblastic leukaemia among patients aged 0–19 years, and survival and early death trends after acute myeloid leukaemia among patients aged 0–39 years. I also investigated whether early death has decreased among young patients after the approval by the US Food and Drug Administration of all-trans retinoic acid (ATRA) for the treatment of acute promyelocytic leukaemia. The overall results of this thesis showed improvement in survival over time for all age groups and subtypes of leukaemia. Early death after acute promyelocytic and myeloid leukaemias declined during the study period. However, these outcomes varied widely by age at diagnosis and were associated with sociodemographic and clinical factors. Racial/ethnical survival inequalities were identified and found to persist even after adjustment for other covariates. These inequalities were more marked among patients of Hispanic (acute lymphoblastic leukaemia) and black race/ethnicity (for acute lymphoblastic and myeloid leukaemias). Patients living in lower socioeconomic neighbourhoods had worse survival than those living in higher socioeconomic neighbourhoods (for acute lymphoblastic and myeloid leukaemias). Early death and worse survival were associated with initial care at hospitals not affiliated with National Cancer Institute-designated cancer centres (for acute myeloid leukaemia) and lack of health insurance (for acute myeloid and promyelocytic leukaemias). Intriguingly, over the 25-year study period, adolescents and young adults with acute leukaemia continued to have worse survival than children. These results suggest that lack of timely access to treatment and suboptimal care have influenced outcome among vulnerable patients. In conclusion, survival and early death after acute leukaemia has greatly improved among young patients in California. However, inequalities in outcomes remain and are likely a result of multiple factors. My studies highlight the importance of population-based data to reveal the actual burden of the disease in this population and help clinicians, policy makers, government, and researchers better understand the predictors of outcomes. I expect my work to contribute to the development of strategies aimed at improving survival from acute leukaemia, especially among vulnerable and disadvantaged patients.
Supervisor: Coleman, M. ; Keogh, R. Sponsor: Children with Cancer UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral