Advances in treatment for acute lymphoblastic leukemia (ALL) have improved survival for most patients with the disease; however, results of the St Jude Lifetime (SJLIFE) Cohort study (Clinialtrials.gov Identifier: NCT0076065) showed that late morbidity burden has changed but is not reduced. The findings from this study were published in Lancet Haematology.

Treatments for children with ALL have evolved over the last 50 to 60 years, with 5-year overall survival rates currently estimated at more than 90%. However, no previous studies have specifically evaluated changes in the prevalence and magnitude of long-term chronic health conditions in this population over time.

The SJLIFE study, a large retrospective cohort study of survivors of childhood cancer involving prospective follow-up, included 980 survivors of pediatric ALL who were treated according to a standard protocol at St Jude Children’s Research Hospital between August 28, 1963, and July 19, 2003. These patients were at least 18 years old at study enrollment and had had at least 10 years of follow-up after ALL diagnosis. A cohort of 272 control patients from the community matched to pediatric ALL survivors by age and sex were also enrolled. Longitudinal clinically based assessments of health outcomes were conducted for all study participants.

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A key finding of the study was that the magnitude of chronic health outcomes has not decreased in this population with more modern-era treatment, although the pattern of chronic health outcomes has changed.

A comparison of late treatment effects in pediatric ALL survivors treated between 1962 and 1991 with those of survivors treated between 1991 and 2007 showed that although the former group was more likely to experience immediately life-threatening conditions and adverse effects involving a number of organ systems (eg, reproductive, neurologic, infectious, gastrointestinal, etc), survivors treated more recently were more likely to experience musculoskeletal problems, likely related to intensive treatment with dexamethasone and asparaginase.

Although reductions in risk of stroke and seizures associated with less chemoradiotherapy use over time were observed, pediatric ALL survivors treated more recently had more sensory and motor neuropathies that may be associated with impairments in physical activity. With respect to endocrine function, more patients treated on older protocols experienced hypothalamic pituitary axis dysfunction, but patients treated more recently were more likely to experience altered glucose metabolism.

Compared with matched control patients, survivors of pediatric ALL had more frequent and more severe chronic health conditions in most organ systems, particularly endocrine, reproductive, and neurologic systems. For example, by age 30 years, survivors of pediatric ALL had an average of 5.4 grade 1 to 4 health conditions and 3.2 grade 2 to 4 health conditions compared with controls where the corresponding average number of grade 1 to 4 and grade 2 to 4 health conditions were 2.0 and 1.2, respectively.

Limitations of this study include the possibility of surveillance bias due to increased screening as a result of longer survival, as well as selection bias since patients included in the study had to return to St Jude Children’s Research Hospital for periodic assessments.

“Although the character of late health outcomes has evolved, the negative effect of therapies on future health remains,” concluded the study authors. Ongoing surveillance and counselling are needed to ensure preservation of health across survivors’ life span.

Reference

Mulrooney DA, Hyun G, Ness KK, et al. 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 [published online May 8, 2019]. Lancet Haematol. doi: 10.1016/S2352-3026(19)30050-X