title: 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.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.
authors: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors: Stefan
authors: S
authors: Essig
authors: School of Public Health, University of Alberta, Edmonton, Alberta, AB, Canada.
authors: Qiaozhi
authors: Q
authors: Li
authors: School of Public Health, University of Alberta, Edmonton, Alberta, AB, Canada.
authors: Yan
authors: Y
authors: Chen
authors: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors: Johann
authors: J
authors: Hitzler
authors: Programs in Clinical Statistics and Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Wendy
authors: W
authors: Leisenring
authors: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors: Mark
authors: M
authors: Greenberg
authors: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Charles
authors: C
authors: Sklar
authors: Departments of Oncology and Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
authors: Melissa M
authors: MM
authors: Hudson
authors: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
authors: Gregory T
authors: GT
authors: Armstrong
authors: Departments of Epidemiology and Cancer Control and Psychology, St Jude Children's Research Hospital, Memphis, TN, USA.
authors: Kevin R
authors: KR
authors: Krull
authors: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
authors: Joseph P
authors: JP
authors: Neglia
authors: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Kevin C
authors: KC
authors: Oeffinger
authors: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
authors: Leslie L
authors: LL
authors: Robison
authors: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors: Claudia E
authors: CE
authors: Kuehni
authors: School of Public Health, University of Alberta, Edmonton, Alberta, AB, Canada.
authors: Yutaka
authors: Y
authors: Yasui
authors: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Electronic address: paul.nathan@sickkids.ca.
authors: Paul C
authors: PC
authors: Nathan
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004522:Educational Status; D004646:Emphysema / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D057187:Independent Living; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D017533:Marital Status; D008875:Middle Aged; D008881:Migraine Disorders / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011159:Population Surveillance; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality*; D012307:Risk Factors; D012678:Sensation Disorders / Q000453:epidemiology; D035781:Siblings; D011795:Surveys and Questionnaires; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult