Clinical presentation of childhood leukaemia: a systematic review and meta-analysis.

OBJECTIVE: Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to diagnosis. DESIGN: We searched MEDLINE and EMBASE for all studies describing presenting features of leukaemia in children (0-18 years) without date or language restriction, and, when appropriate, meta-analysed data from the included studies. RESULTS: We screened 12 303 abstracts for eligibility and included 33 studies (n=3084) in the analysis. All were cohort studies without control groups. 95 presenting signs and symptoms were identified and ranked according to frequency. Five features were present in >50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%). An additional eight features were present in a third to a half of children: recurrent infections (49%), fatigue (46%), limb pain (43%), hepatosplenomegaly (42%), bruising/petechiae (42%), lymphadenopathy (41%), bleeding tendency (38%) and rash (35%). 6% of children were asymptomatic on diagnosis. CONCLUSIONS: Over 50% of children with leukaemia have palpable livers, palpable spleens, pallor, fever or bruising on diagnosis. Abdominal symptoms such as anorexia, weight loss, abdominal pain and abdominal distension are common. Musculoskeletal symptoms such as limp and joint pain also feature prominently. Children with unexplained illness require a thorough history and focused clinical examination, which should include abdominal palpation, palpation for lymphadenopathy and careful scrutiny of the skin. Occurrence of multiple symptoms and signs should alert clinicians to possible leukaemia.

The signs, symptoms and help-seeking experiences of neutropenic sepsis patients before they reach hospital: a qualitative study.

PURPOSE: Neutropenic sepsis (NS) is a medical emergency in which urgent treatment with antibiotics is known to improve outcomes, yet there are minimal data about what happens to patients with NS before they reach hospital. We aimed to examine the pre-hospital experiences of patients with NS, identifying its early presenting features and exploring the factors potentially delaying patients' arrival at hospital. METHODS: We conducted in-depth, qualitative interviews with 22 cancer patients admitted to hospital for treatment of NS and 10 patient carers. The setting was a tertiary referral centre in Southern England. RESULTS: Thirty seven percent of patients took over 12 h to present to hospital after symptom onset. The mean delay in presentation was 11 h (range 0-68 h). Thematic analysis of the interviews, using grounded theory, revealed wide-ranging, potentially modifiable factors delaying patients' presentation to hospital. For example, information provided to patients about NS from different sources was inconsistent, with 'mixed messages' about urgency triggering delays. All patients self-monitored their temperature and understood the implication of a fever but few appreciated the potential significance of feeling unwell in the absence of fever. Attempts to obtain treatment were sometimes thwarted by nonspecialists' failure to recognise possible neutropenia in a patient with apparently mild signs, and several patients with NS were discharged without treatment. Some patients denied their symptoms to themselves and others to avoid hospital admission; palliative patients seemed particularly prone to these attitudes, while their carers were keen to seek medical attention. CONCLUSIONS: This investigation of patients' and carers' experiences of NS identifies numerous strategies for improving patient education, support and pre-hospital management, all of which may reduce pre-hospital delays and consequently decrease morbidity and mortality from NS.

'Shouting from the roof tops': a qualitative study of how children with leukaemia are diagnosed in primary care.

OBJECTIVES: To investigate the prehospital presentation of paediatric leukaemia and identify the disease and non-disease related factors which facilitate or impede diagnosis. DESIGN: Thematic analysis of qualitative semistructured interviews. SETTING: One tertiary referral centre in Southern England. PARTICIPANTS: 21 parents and 9 general practitioners (GPs) of 18 children (<18-year-old) with a new diagnosis of acute leukaemia. RESULTS: The majority of children were first seen by GPs before the characteristic signs and symptoms of leukaemia had developed. In their absence, behavioural cues such as the child becoming apathetic or 'not themselves' often triggered parents to seek medical help. Most GPs were unclear about the nature and severity of the child's presentation: then, safety netting, thorough history-taking and examination, and reliance on contextual information about the parents or from prior hospital paediatrics experience were used to manage diagnostic uncertainty. The nature of the doctor-parent relationship helped and hindered the diagnostic pathway. GPs' prior perceptions of parents as being 'sensible' or 'worriers' influenced how gravely they treated parental concerns, with 'worriers' being taken less seriously. Some parents believed GPs failed to listen to their anxieties and discounted their expert knowledge of their child. Specific delay factors included lack of continuity of GP; some GPs' reluctance to take blood from children; and some parents feeling unable to voice effectively their concerns. CONCLUSIONS: The presentation of paediatric leukaemia in primary care differs from that described in many hospital studies, with greater diversity and intermittency of symptoms, and the frequent absence of 'red flags' of serious illness. A wide range of non-disease related factors potentially delay the diagnosis of paediatric leukaemia, including tensions in the doctor-patient relationship and the doctors' cognitive biases. The identification and attempted modification of these factors may minimise diagnostic delay more successfully than raising awareness of 'red flags' of disease.

Haemolytic uraemic syndrome in a patient with acute lymphoblastic leukaemia.

We describe a patient diagnosed with haemolytic uraemic syndrome (HUS) during long-term maintenance therapy for childhood acute lymphoblastic leukaemia (ALL). He rapidly developed renal failure, hypertension and profound thrombocytopenia. Despite suffering a large intracerebral haemorrhage, he made a full recovery without residual neurological or renal deficit. His case raises the question of whether ALL or its treatments predispose an individual to developing HUS.