What is a bone marrow aspirate and why is it so painful?
Blood cells are manufactured in the bone marrow space and examination of these cells in myeloma is performed to identify an increase in the number of plasma cells which is one of the cardinal features used to confirm the diagnosis. In order to obtain these cells for examination the clinician needs to perform a bone marrow aspirate. The thin “skin” that coats the bone surface and carries the small nerves responsible for carrying sensation and pain, is anaesthetised using local anaesthetic. A special needle is then inserted into the bone. Marrow is withdrawn with a syringe attached to the needle, like a blood test. When we are born, most of our bones contain marrow, but as we get older the marrow in our limbs is replaced by fat and the majority of the marrow resides in the spinal vertebrae, ribs, pelvis and breast bone. Samples are normally taken from the pelvis or breastbone and only very rarely from the spine. Although aspiration is uncomfortable, the pain that people may experience is due to the pressure that is exerted when the doctor draws back on the syringe attached to the special needle. This should only be a transient pain that is relieved as soon as the pressure is released after 3-4 seconds. Often the doctor may take an additional small sample of bone (a trephine) inside the needle to give extra information about the state of the marrow. The maneuvering of the needle in the bone to break off the sample inside the needle may cause an unusual sensation but normally this only lasts a few extra seconds. Once the anaesthetic has worn off there may be an ache at the site of the aspirate, best treated using paracetamol, and it should have resolved after about 24 hours.
What are the most recent developments in thalidomide?
Thalidomide was first used in patients with myeloma about 3 years ago for patients with relapsed or refractory disease that was not responding to chemotherapy. Since the first report in the literature in 1999 there have been a number of studies which have confirmed the excellent results seen in the first study. More recently there has been a report of the use of thalidomide for patients who have not been previously treated with any chemotherapy with encouraging results. Thalidomide is a very important drug because it is not a chemotherapy drug and works in a different way. It has been known for 10 years that thalidomide interfered with new blood vessel formation and that this is an important mechanism for the survival and spread of solid tumours. It was only more recently however, that it became clear how important new blood vessel formation is in myeloma and other blood tumours. Although this may be an important mechanism in the anti-tumour activity of thalidomide, the effects of treatment are seen after only a few weeks of treatment, strongly suggesting that other mechanisms may be as, or more, important. It is now clear, however, that thalidomide also affects the secretion of factors that affect the survival and proliferation of myeloma cells by an effect directly on the myeloma cell itself, and indirectly via cells which have an immunological effect in controlling cell growth.
The main side effects of thalidomide are nerve damage, constipation, skin rashes, and somnolence. Most of these side-effects are manageable with simple medications, but in an attempt to reduce the side effects and improve the responses to this type of drug, the company that manufactures thalidomide have modified the structure of thalidomide and produced 2 new compounds. One of these agents, CC5013 (Revimid), has been used in patients in the United States and the other, CC4047 (Actimid), has been used in early clinical studies by ourselves at Guys & St Thomas’ Hospital, London. Early results are very encouraging and it is hoped that further studies will be undertaken in this country later in the year with both CC4047 and CC5013.
Further studies are needed to ascertain the optimum dose of thalidomide and when best to use it in the course of the disease. A number of studies are also being undertaken by the UK Myeloma Forum (UKMF) and Medical Research Council (MRC) looking at the use of thalidomide in combination with other chemotherapy agents in an attempt to optimise its benefits.
What is the difference between X-ray, MRI and CT, and how often should you have them?
- X-rays use radiation to produce an image on a piece of X-ray film like the negatives you get when you develop your holiday photographs.
- A CT uses the same kind of radiation as a plain X-ray but the information is fed into a computer to produce a cross-sectional image.
- MRI does not use radiation but instead employs magnetic fields and radio waves to produce a cross-sectional image similar to that of a CT.
Each of these techniques has their own limitations and the most appropriate investigation will depend upon what the doctor is looking to define. Hence CT scans are useful for identifying soft tissue ‘lumps’ or masses of myeloma and can be very helpful to define myeloma in the chest particularly if it is arising from the spine or ribs. MRI is better for identifying disease in the bone itself and may be positive when the plain X-ray skeletal survey is negative, which is helpful to know when making decisions on when to initiate treatment.
On other occasions, radiological investigations are performed in an attempt to identify a complication of the disease such as an infection. These may commonly involve the chest, and plain X-rays and CT scans are excellent for identifying infection in this site. MRI scans on the other hand are not useful in this site but may be more helpful for investigating the liver or spleen.
The choice of investigation therefore depends upon the clinical situation and should be tailored to the individual patient’s needs.
Dr. Schey is Consultant Haematologist at Guy’s Hospital, London, England