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Excess Risk of Chronic Late Effects of Treatment in Children With Standard-Risk ALL

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Key Points

  • Survivors were at increased risk of any chronic health condition and severe chronic health conditions.
  • Survivors did not differ from siblings in household income, educational attainment, marriage status, or independent living.

Given the changes in treatment of children with acute lymphoblastic leukemia (ALL), the risk of late effects in those treated with current protocols may be different from that in children treated decades ago. In a study of survivors of childhood standard-risk ALL reported in The Lancet Oncology, Essig et al found a small but quantifiable excess risk of chronic health effects in those diagnosed between 1970 and 1986, estimating that 107 patients would need to be followed for 1 year to find one excess chronic health condition.

Study Details

The study included 556 5-year survivors of newly diagnosed standard-risk ALL in the Childhood Cancer Survivor Study cohort who were aged 1 to 9.9 years at diagnosis between 1970 and 1986. Patients had to have received treatment consistent with contemporary standard-risk protocols. Outcomes in patients were compared with those in a sibling cohort (n = 2,232) and in the general U.S. population using Surveillance, Epidemiology and End Results (SEER) data.

Mortality and Second Neoplasms

Median follow-up of survivors from 5 years after diagnosis was 18.4 years (range = 0–33 years). A total of 28 patients (5%) had died, with 16 deaths (57%) being due to causes other than ALL recurrence. Compared with the general population, survivors were at increased risk of nonrelapse mortality (standardized mortality ratio = 2.0, 95% confidence interval [CI] = 1.1–3.2), but there were no significant differences in risk of death due to a new malignancy, cardiac disease, pulmonary disease, or external causes (eg, homicide, suicide, accident). Six (1%) survivors developed a second malignant neoplasm (standardized incidence ratio = 2.6, 95% CI = 1.0–5.7).

Chronic Health Disorders

Comparison of chronic health disorders in survivors and siblings showed that survivors had increased risk of any disorder (grade 1–5; relative risk [RR] = 1.3, P = .0005) and any severe disorder (grade 3–5; RR = 2.0, P < .0001) after adjustment for sex and age at follow-up. It was estimated that 117 and 415 survivors would need to be followed for 1 year to detect one excess chronic disorder and one excess severe chronic disorder, respectively. Survivors also had increased risk of more than one chronic disorder (grade 1–5; RR = 1.6, P < .0001).

With regard to individual disorders, survivors had increased adjusted risk vs siblings for osteoporosis/osteopenia (odds ratio [OR] = 5.5, P = .0089), growth hormone deficiency (OR = 13.9, P = .0012), cataracts (OR = 5.0, P = .0032), and short stature (OR = 3.9, P < .0001), but not for second malignant neoplasm, congestive heart failure/cardiomyopathy, stroke/cerebrovascular disease, grade 1 or 2 hypothyroidism, obesity, or neurocognitive deficits. 

General Health Status and Sociodemographic Outcomes

Survivors were at increased risk of poor functional status vs siblings (OR  = 1.9, P = .041), but no differences were found in general health, mental health, or activity limitation or in the sociodemographic measures of household income, education level, married status, independent living, or insurance coverage.

The investigators concluded, “The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted.”

Paul C. Nathan, MD, of The Hospital for Sick Children, Toronto, is the corresponding author for The Lancet Oncology article.

The study was funded by the National Cancer Institute, American Lebanese-Syrian Associated Charities, and Swiss Cancer Research. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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