ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 9.1 | DOI: 10.1530/ey.16.9.1

The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude lifetime cohort study

Mulrooney DA, Hyun G, Ness KK, Bhakta N, Pui CH, Ehrhardt MJ, Krull KR, Crom DB, Chemaitilly W, Srivastava DK, Relling MV, Jeha S, Green DM, Yasui Y, Robison LL & Hudson MM



To read the full abstract: Lancet Haematol. 2019 Jun; 6(6): e306.

The St Jude Lifetime (SJLIFE) Cohort is a retrospective cohort of childhood cancer survivors (CCS), who are followed prospectively in order to evaluate long-term health outcomes. This study evaluated chronic health conditions in 980 childhood lymphoblastic leukaemia survivors of the SJLIFE cohort, compared to 272 matched community controls. Survivors were diagnosed with paediatric acute lymphoblastic leukaemia between Aug 28th 1963 and July 19th 2003 at St Jude Children’s Research Hospital. Enrolled patients were aged ≥18 years old at recruitment and had at least 10 years of follow-up after diagnosis. The large sample size and the accurate data collection are the main strengths of the study that allow a reliable analysis of the changes in the prevalence of late outcomes and the identification of changing patterns in late outcomes, concurrently with evolving treatment modalities.

Different disorders of attention and cognitive and executive performance have become increasingly more common in patients than in controls in more recent years. Conversely, a decrease in health conditions that are immediately life-threatening, as stroke and seizures, was observed, concurrently with an increased incidence of milder conditions as chronic peripheral neuropathy. The incidence of pituitary defects showed a decreasing trend with time, but growth hormone deficiency and hypogonadism were remained more common in survivors than in controls, even in the most recent years. Impaired glucose metabolism became more frequent with time, and a trend towards obesity was registered in both survivors and controls. Compared to previous years, survivors treated in recent years showed a higher prevalence of musculoskeletal disorders, probably related to a reduced bone mineral density. This finding correlated with an impairment of mobility and aerobic function. Attention and executive function improved as treatment protocols restricted chemo-radiotherapy. Among survivors who did not receive radiotherapy, attention did not differ from population normative data or controls, except for a less focused attention.

Treatment protocols of childhood acute lymphoblastic leukaemia have significantly changed during the last three decades, with a progressive improvement of overall survival. The cumulative burden of severe health conditions involving multiple organ systems has decreased, after the elimination of cranial-spinal and cranial radiotherapy from treatment protocols. The pattern of toxic effects has remarkably changed over time, with a reduction of early life-threatening conditions. Late morbidities, as chronic musculoskeletal and endocrine disorders, predominate in patients treated more recently. Maintaining health status and quality of life still requires careful medical surveillance, counselling, and lifestyle changes.