The following signs and symptoms should be investigated.

Most patients are asymptomatic when they are diagnosed. Often CLL is recognised after lymphocytosis is found during a routine blood test performed for other reasons. Symptoms can include (Hallek et al. 2018):

• painless swelling of lymph nodes that may fluctuate in size but don’t completely resolve (within six to 12 weeks) – this can affect any lymph nodes but often occurs around the neck
• unexplained weight loss of more than 10 per cent of body weight within the past six months
• fever without signs of infection (rarely)
• severe night sweats without signs of infection (uncommon)
• extreme fatigue (prevents person from working or doing their usual activities)
• frequent infections or first onset of herpes zoster reactivation. Other signs include (Binet et 1981; Rai et al. 1975):
• lymphadenopathy – 50 to 90 per cent of patients experience enlarged lymph nodes (cervical, supraclavicular and axillary are the most common areas)
• splenomegaly – 25 to 55 per cent of cases
• hepatomegaly – 15 to 25 per cent of

Suggestive laboratory abnormalities

If any of the following abnormalities are found, CLL should be investigated as a possible underlying cause:

• hypogammaglobulinemia – present in a quarter of patients at initial diagnosis and becomes more common as the disease progresses (Parikh et 2015)
• autoimmune haemolytic anaemia
• immune

The presence of multiple signs and symptoms, particularly in combination with other underlying risk factors, indicates an increased risk of CLL.

General practitioner examinations and investigations should include:

• history and physical exam including careful palpation of all lymph node areas, spleen and liver
• full blood count and manual film examination
• flow cytometry to confirm clonal nature of lymphocytes
• urea, electrolytes, uric acid and creatinine
• liver function tests
• serum immunoglobulin levels and direct antiglobulin test (Coombs’ test). Tests that are not usually required:
• lymph node biopsy is generally not necessary to diagnose CLL, even if lymphadenopathy is present clinically or on imaging
• routine imaging is not recommended – imaging should only be performed when there are concerns around local symptoms, compression or very bulky nodes to exclude a local complication such as hydronephrosis or vascular compression.

Any patient with symptoms suspicious of CLL can be referred for specialist assessment as first line. If the diagnosis of CLL is confirmed or the results are inconsistent or indeterminate, referral to a haematologist for ongoing management is warranted.

Patients should be enabled to make informed decisions about their choice of specialist and health service. General practitioners should make referrals in consultation with the patient after considering the clinical care needed, cost implications (see referral choices and informed financial consent on page 9), waiting periods, location and facilities, including discussing the patient’s preference for health care through the public or the private system.

Referral for suspected or diagnosed CLL should include the following essential information to accurately triage and categorise the level of clinical urgency:

• important psychosocial history and relevant medical history
• family history, current symptoms, medications and allergies
• results of current clinical investigations (imaging and pathology reports)
• results of all prior relevant investigations
• notification if an interpreter service is

The following clinical prioritisation criteria are used to triage patients with CLL.

According to the CLL International Working Group guidelines, updated in 2018, CLL is diagnosed when there are more than 5.0 × 109/L B lymphocytes in the peripheral blood for at least three months and clonality is confirmed by demonstrating immunoglobulin light-chain restriction on flow cytometry (Hallek et al. 2018). Lower levels of clonal B-cell lymphocytosis may suggest the related disorder known as monoclonal B-cell lymphocytosis and should also be referred to a specialist.

Referral to a specialist should take place once significant lymphocytosis and/or a leukaemic cell population is identified.

In most cases, CLL is diagnosed incidentally based on minor peripheral blood lymphocytosis in patients who are either well or have minimal symptoms. In these typical cases, urgent referral and work-up are not required to prevent physical deterioration. However, the differential diagnosis of CLL can be very stressful for patients, so a timely referral to enable clarity and reassurance is an important consideration.

It is also important to assess for uncommon but more medically urgent cases.

Cases that require prompt referral to a specialist within 72 hours are:

• severe/(symptomatic) thrombocytopenia or anaemia such as haemoglobin under 70 g/L or platelets under 50 × 109/L, or
• bulky (> 5 cm) or locally compressive

The specialist should then assess the patient within 72 hours, or sooner if medically urgent based on specific circumstances.

In more typical cases where referral is less urgent, it will be important for the general practitioner to provide reassurance and clearly explain the slow-growing nature of CLL, noting that typically intervention is not needed for several years, and up to one-third of patients may never require treatment (Scarfò et al. 2016). This is in contrast to acute forms of leukaemia.

Many services will reject incomplete referrals, so it is important that referrals comply with all relevant health service criteria.

If access is via online referral, a lack of a hard copy should not delay referral.

The specialist should provide timely communication to the general practitioner about the consultation and should notify the general practitioner if the patient does not attend appointments.

Aboriginal and Torres Strait Islander patients will need a culturally appropriate referral. To view the optimal care pathway for Aboriginal and Torres Strait Islander people and the corresponding quick reference guide, visit the Cancer Australia website. Download the consumer resources – Checking for cancer and Cancer from the Cancer Australia website.