title: Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records.
abstract: BACKGROUND
  Leukaemia is the eleventh commonest UK cancer. The four main subtypes have different clinical profiles, particularly between chronic and acute types.
  
  
  OBJECTIVE
  To identify the symptom profiles of chronic and acute leukaemia in adults in primary care.
  
  
  METHODS
  Matched case-control studies using Clinical Practice Research Datalink records.
  
  
  METHODS
  Putative symptoms of leukaemia were identified in the year before diagnosis. Conditional logistic regression was used for analysis, and positive predictive values (PPVs) were calculated to estimate risk.
  
  
  RESULTS
  Of cases diagnosed between 2000 and 2009, 4655 were aged ≥40 years (2877 chronic leukaemia (CL), 937 acute leukaemia (AL), 841 unreported subtype). Ten symptoms were independently associated with CL, the three strongest being: lymphadenopathy (odds ratio [OR] 22, 95% confidence interval [CI] = 13 to 36), weight loss (OR 3.0, 95% CI = 2.1 to 4.2), and bruising (OR 2.3, 95% CI = 1.6 to 3.2). Thirteen symptoms were independently associated with AL, the three strongest being: nosebleeds and/or bleeding gums (OR 5.7, 95% CI = 3.1 to 10), fever (OR 5.3, 95% CI = 2.7 to 10), and fatigue (OR 4.4, 95% CI = 3.3 to 6.0). No individual symptom or combination of symptoms had a PPV >1%.
  
  
  CONCLUSIONS
  The symptom profiles of CL and AL have both overlapping and distinct features. This presents a dichotomy for GPs: diagnosis, by performing a full blood count, is easy; however, the symptoms of leukaemia are non-specific and of relatively low risk. This explains why many leukaemia diagnoses are unexpected findings.
authors.affiliation: University of Exeter Medical School, Exeter.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Shephard
authors.affiliation: North Wales Centre for Primary Care Research, Bangor University, Wrexham.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Neal
authors.affiliation: Department of Primary Care Health Sciences, University of Oxford, Oxford.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Rose
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Walter
authors.affiliation: University of Exeter Medical School, Exeter.
authors.forename: Willie
authors.initials: W
authors.lastname: Hamilton
mesh_terms: D000208:Acute Disease / Q000401:mortality*; D000367:Age Factors; D016022:Case-Control Studies; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011320:Primary Health Care / Q000706:statistics & numerical data; D011787:Quality of Health Care; D012196:Review Literature as Topic; D018570:Risk Assessment; D015996:Survival Rate; D006113:United Kingdom / Q000453:epidemiology
keywords: acute lymphoblastic leukaemia; acute myeloid leukaemia; chronic leukaemia; diagnosis; primary health care