Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort

Stefan Essig, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Qiaozhi Li, School of Public Health, University of Alberta, Edmonton, Alberta, AB, Canada.
Yan Chen, School of Public Health, University of Alberta, Edmonton, Alberta, AB, Canada.
Johann Hitzler, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Wendy Leisenring, Programs in Clinical Statistics and Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Mark Greenberg, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Charles Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Melissa M. Hudson, Departments of Oncology and Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
Gregory T. Armstrong, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.Follow
Kevin R. Krull, Departments of Epidemiology and Cancer Control and Psychology, St Jude Children's Research Hospital, Memphis, TN, USA.
Joseph P. Neglia, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Kevin C. Oeffinger, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Leslie L. Robison, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
Claudia E. Kuehni, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Yutaka Yasui, School of Public Health, University of Alberta, Edmonton, Alberta, AB, Canada.Follow
Paul C. Nathan, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Electronic address: paul.nathan@sickkids.ca.

Abstract

BACKGROUND: Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. METHODS: We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. FINDINGS: We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. INTERPRETATION: 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. FUNDING: National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

Publication Title

The Lancet. Oncology

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