Information Pathway. Myeloma tests and investigations. Paraprotein measurement



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Information Pathway Myeloma UK Broughton House 31 Dunedin Street Edinburgh EH7 4JG Tel: + 44 (0) 131 557 3332 Fax: + 44 (0) 131 557 9785 Myeloma Infoline 0800 980 3332 www.myeloma.org.uk Charity No. SC 026116 Myeloma tests and investigations In order to diagnose and monitor your myeloma, several tests and investigations need to be carried out. Tests and investigations are done to: Establish a diagnosis Help determine a treatment plan and monitor progress Detect myeloma and treatment related complications Detect early signs of relapse following treatment Myeloma is a very individual cancer and results from these tests can vary considerably from patient to patient. It is not enough just to make a diagnosis; it is critical to have an accurate picture of the myeloma in each patient before an appropriate treatment plan can be developed. This information sheet provides an overview of some of the tests that you are likely to have as a myeloma patient. Paraprotein measurement Paraprotein is the specific antibody that is produced by and is unique to an individual patient s myeloma cells. Measurement of paraprotein levels is important both in diagnosing myeloma and as an indicator of changes in it s activity. For this reason, paraprotein measurements are done regularly to see how well treatment is working and to check that the myeloma is remaining stable during periods when you are not receiving active treatment. Paraprotein levels will therefore fall with successful treatment and increase when the myeloma becomes active again. What tests are used to measure paraprotein? Paraprotein measurement can be made on either a blood and / or urine sample. A test called protein electrophoresis is carried out to measure the levels of paraprotein present. Immunofixation is a similar test to electrophoresis but it is more sensitive. This test may be carried out to investigate the results of an electrophoresis test in more detail and it can be used to identify the type of paraprotein the myeloma cells are producing. The different types of paraprotein are described in more detail in the Types of myeloma information sheet. You can get a copy of this information sheet from your doctor or nurse. Myeloma Awareness Week 21 28 June

Immunofixation is the international gold standard test for detecting low levels of paraprotein in blood and urine. Part of the definition of a complete response to myeloma treatment is that the blood and urine should both be negative for paraprotein when tested by immunofixation. Historically, free light chains (small, unbound parts of the paraprotein) could only be measured in urine but in 2003 a test became available to measure free light chains in blood. In this case a blood test called the Serum Free Light Chain Assay (SFLCA or Freelite test) can be used to measure free light chains in your blood. The value of this assay is that it can detect abnormal blood levels of free light chains derived from the myeloma cells at levels substantially below those when the free light chains first spill over into the urine. This test is particularly important in patients in whom there is no whole antibody paraprotein to monitor. This is termed light chain only or non-secretory myeloma. If you have no paraprotein detectable after treatment you are normally considered to be in complete remission. If your paraprotein has fallen and is still detectable and stable after treatment you are normally considered to be in partial remission, also called plateau phase. Complete remission is unusual except after high-dose therapy and stem cell transplantation. X-rays of skeleton As myeloma can thin the bones, one of the first investigations performed is often a skeletal survey. This is a series of X-rays used to detect any bone damage and includes X-rays of the spine, skull, chest, pelvis and the upper bones of the arms and legs. X-rays can show areas of thinning, lytic lesions (areas of bone damage) and fractures. Other methods used to image the bones If the skeletal survey using X-rays does not show up any area of damage, and myeloma bone disease is suspected, other imaging techniques can be used which provide more detail. These additional techniques include: Magnetic resonance imaging (MRI): this is the most commonly used imaging test after skeletal survey. MRI may be used if X-rays are inconclusive or more detailed testing is needed of an area such as the spine Computerised tomography (CT): CT scans can also be used to assess myeloma bone disease in certain situations e.g. assessing soft tissue involvement and radiotherapy planning. MRI is, however, considered preferable to CT scans when assessing bone FDG / PET scanning: whole body FDG / PET (fluoro-deoxyglucose positron emission tomography) is a relatively new, albeit less routine imaging technique in which a low-dose radioactive drug is injected. This drug collects at an area where there are myeloma cells and therefore highlights areas of the body where myeloma cells are present. It is not routinely used in myeloma but is applicable in certain situations where disease outside of the bone marrow is suspected and other imaging techniques have proven inconclusive What will bone imaging involve? X-rays, MRI and CT should be pain free for the patient. However, you may have to lie still for a period of time while the X-ray is carried out. FDG / PET scanning will involve the injection of a drug into the back of the hand or into the arm and although this may be uncomfortable for the patient, the injection is generally no more painful than a blood test. Information Pathway Myeloma tests and investigations 2

Bone marrow biopsy aspiration and trephine biopsy This will be performed in virtually all patients to confirm a diagnosis of myeloma. Local anaesthetic is used and two types of specimens are obtained. A liquid specimen, which is called the bone marrow aspirate and a small solid core of bone and bone marrow which is called a trephine biopsy. The purpose of this test is to determine the total number of plasma cells present in the marrow and to determine whether they are normal or abnormal. Plasma cell numbers are typically expressed as a percentage of total bone marrow cells and: Normal bone marrow has less than 5% abnormal plasma cells Bone marrow in myeloma patients may have between 10% and 90% abnormal plasma cells in their bone marrow This test may also be carried out at the beginning and end of treatment to measure the change in the number of plasma cells present in the bone marrow. Increasingly the myeloma cells are also sent for genetic testing as there are a number of genetic abnormalities which may help guide treatment. After treatment, assessing the marrow aspirate with sensitive tests to detect the presence or absence of very small numbers of residual myeloma cells can help assess the quality of response. Blood tests Throughout your treatment, you will have regular blood tests. As mentioned, blood samples are used to measure the level of paraprotein and / or free light chains present in the blood. This is a direct measure of the activity of your myeloma and is used to assess response to treatment. Numerous other blood tests are also performed to monitor the effects of your myeloma and potential adverse effects of treatment. Full blood count Part of every blood sample is normally used to count the make-up of some of the important cells in your blood: Red blood cells which transport oxygen (this is usually expressed as the haemoglobin level in the blood) White blood cells which help fight infection Platelets which help the blood to clot These cell counts are important because: The red blood cell count tells your doctor if you are anaemic The white blood cell count tells your doctor if you are at a higher than normal risk of infection The number of platelets tells your doctor whether you are at risk of bleeding or bruising more easily than normal Kidney function Kidney function can be affected by certain unique features associated with myeloma and also by the effects of some of its treatments. Information Pathway Myeloma tests and investigations 3

Blood tests are used to help measure the levels of urea and creatinine which are waste products that are normally filtered out by the kidney. High levels of urea and creatinine in the blood indicate poor kidney function. Calcium measurement Calcium is a mineral which is normally found in the bone. In patients with active myeloma bone disease, calcium is released from the bone into the blood stream. This can lead to higher levels of calcium in the blood. Blood tests can be used to measure and monitor the level of calcium present in your blood. Albumin measurement Albumin is a type of protein that normally makes up most of the protein found in the blood, but in myeloma, hormones (or cytokines) produced by the myeloma suppress the albumin production in the liver. Blood tests can be used to measure and monitor the level of albumin present in your blood. Beta 2 microglobulin A blood test can also be useful to detect levels of a molecule called beta 2 microglobulin (ß2M). ß2M is one of the most important indicators of both the level and activity of the myeloma and therefore is crucial in determining the prognosis of individual cases. Normal blood test results Blood tests Test name Normal range* Units Notes Full blood count Urea, electrolytes and creatinine White cell count 4.0 11.0 x 10 9 /L A low count makes you less able to fight infections Red cell count (men) Red cell count (women) Haemoglobin (men) Haemoglobin (women) 4.5 6.5 x 10 12 /L A low red cell count is anaemia, which can cause fatigue 3.9 5.6 x 10 12 /L 13.5 18.0 g/dl A low haemoglobin level, also called anaemia, can cause fatigue 11.5 16.0 g/dl Platelets 150 400 x 10 9 /L A low count makes you bruise or bleed easily Urea 2.5 6.7 mmol/l Measure of kidney function Creatinine 70 150 µmol/l Measure of kidney function Calcium (total) 2.12 2.65 mmol/l Raised by myeloma bone disease Proteins Albumin 35 50 g / L Often lowered in myeloma because of presence of paraprotein Total protein 60 80 g / L Often raised in myeloma because of amount of paraprotein Paraprotein 0 g / L Abnormal protein found in several conditions, including myeloma Table 1: Average normal blood test results Information Pathway Myeloma tests and investigations 4

Table 1 provides a summary of some of the average normal ranges for some of the blood tests that have been described. It should be noted that the results presented in the table are for average ranges and that each hospital laboratory has its own normal range of values. Explanation of units g/dl how many grams there are in a decilitre (100 millilitres) of blood g/l x 10 9 /L x 10 12 /L mmol/l µmol/l *mole how many grams there are in a litre of blood how many thousand million cells there are in a litre of blood how many million million cells there are in a litre of blood how many thousandths of a mole* there are in a litre of blood how many millionths of a mole there are in a litre of blood a standard measurement for the weight of any chemical Please note that doctors do not use a litre of blood to make these measurements; they just take a small sample (a few millilitres) and then multiply the results. The future On completion of a wide range of tests, your doctor should have a clear and in-depth picture of the specific characteristics of your myeloma. With this information the doctor can determine the stage of the myeloma and develop a treatment plan. The different stages of myeloma are described in more detail in the Staging of myeloma information sheet. You can get a copy of this information sheet from your doctor or nurse. Research into myeloma and its treatments is advancing all the time. In the future it is likely that it will be possible to look at an individual s genetics to diagnose and treat myeloma. This will result in the best possible treatment being identified for each patient and will help to improve the response to treatment. Other information available from Myeloma UK Myeloma UK has a range of Essential Guides, Infoguides and Infosheets available covering many areas of myeloma, its treatment and management. To order your free copies call our Myeloma Infoline on 0800 980 3332. This information is also available on our website at www.myeloma.org.uk To talk to someone about any aspect of myeloma, call our Myeloma Infoline on 0800 980 3332. The Myeloma Infoline is open from Monday to Friday, 9am to 5pm and is free to phone from anywhere in the UK. From outside the UK, call +44 (0) 131 557 9988 (charged at normal rate). About Myeloma UK Myeloma UK is the only organisation dealing exclusively with myeloma and its related disorders in the UK. Our broad and innovative range of services cover every aspect of myeloma from information and support to improving standards of treatment and care through research, education, campaigning and raising awareness. Information Pathway Myeloma tests and investigations 5

Our strategy is to take an integrated approach to systematically address the barriers and challenges that are slowing down myeloma research and the development of, and access to, new treatments, optimal care, information and support. We receive no government funding and rely almost entirely on voluntary donations and fundraising activities. With Myeloma UK you can Call our Myeloma Infoline on 0800 980 3332 for information, practical advice, emotional support and a listening ear Get free Infopacks, Infoguides and Infosheets about myeloma Learn about myeloma from experts and meet others affected by myeloma by attending Patient and Family Myeloma Infodays Subscribe to our newsletter Myeloma Matters Visit our website www.myeloma.org.uk Join a Myeloma Support Group Author: Anne-Marie Haughey Research and Clinical Information Writer, Myeloma UK Issue date: August 2010 Myeloma UK Broughton House, 31 Dunedin Street, Edinburgh EH7 5JG Tel: + 44 (0) 131 557 3332 Fax: + 44 (0) 131 557 9785 Email: myelomauk@myeloma.org.uk www.myeloma.org.uk Charity no. SC 026116 Information Pathway Myeloma tests and investigations 6