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Myeloma and plasmacytoma: symptoms and treatment

Myeloma and plasmacytoma

Multiple myeloma is a cancer of the plasma cells (derivative cells of the lymphoid system and normally a part of the bone marrow mix of cells - their normal function is to make antibodies against various specific foreign protein antigens). Specifically, each patient’s plasmacytoma/myeloma has arisen from one malignant clone, testified by the fact that the immunoglobulin/antibody secreted from that myeloma is identical from each cell; indeed, this is the best evidence in the subject of Oncology that cancer does have a single cell/clone origin. Where the clone of cells remains localised to one site we refer to the disease as plasamacytoma, whereas, when there are many lesions due to spread of the malignancy to multiple bones and marrow, we refer to the disease as multiple myeloma. 


In 56% of cases of myeloma, the immunoglobulin is IgG, it is IgA in 27%, IgD in 1.5% and IgM in 0.2%. In 17% of cases, there is no whole immunoglobulin secreted but a Bence Jones protein (a part of the immunoglobulin molecule, specifically the light chain part) is detectable in the urine. The myeloma is then termed IgG myeloma, IgA myeloma etc.


Incidence of myeloma and plasmacytoma

Incidence and predisposing factors

Multiple myeloma is a disease caused by a malignant clone of plasma cells; the lineage of bone marrow cells that physiologically have the function of making antibodies (the immune serum proteins that attach to specific foreign proteins and allow their immune destruction). There are several types of antibody, all of them immunoglobulins (Ig A,D,E,G, and M) but only IgA,D,G, and M, need to be considered in this context.


Multiple myeloma accounts for 1% of cancer in the UK with 3000 cases per year, with a slightly higher incidence in the Afro-Caribean population. There is a slight male preponderance of the disease. The mean age of clinical presentation is 70 years and the incidence seems to be slightly increasing in recent years.


The photo shows a cluster of malignant plasma cells from a bone marrow sample, taken from a patient with myeloma and viewed (after staining of a smear on a microscope slide) under the high power of a microscope.


Symptoms of myeloma and plasmacytoma

The most common cause of presentation to the doctor is bone pain, usually pain in the spine where the disease has weakened the vertebra and caused painful and sometimes collapsed vertebrae, pinching or crushing the exiting nerve roots from the spinal canal. Sometimes, the collapsed vertebrae may compromise the integrity of the spinal canal itself causing pressure on the spinal cord and leading to weakness in the legs, which is a serious development that is always taken very seriously. 


Alternatively, as most of the marrow containing bones are 'softened' by the myeloma process, the patient may present with a fracture of a long bone (e.g. the upper arm bone or leg bone), following minor trauma.


Other less common presentation symptoms relate to anaemia due to the disease 'over-running' the bone marrow (and an increased bleeding tendency may have the same origin) or kidney failure (a well recognised secondary phenomenon in this disease).


Metabolic complications account for the minority of cases and include a very high serum calcium (hypercalcaemia) or a hyperviscosity state due to an excess circulating IgM, both these events causing drowsiness and general ill health. The excess of IgM occurs in a variant disease called Waldenstrom’s macroglobulinaemia.


Lastly and very importantly, these patients are very immune deficient and are at high risk of infection. Indeed, they may present with a serious infection.


Treatment of myeloma and plasmacytoma

Some patients with early or smouldering myeloma can be watched carefully without therapy and their long term survival will not be jeopardised if the careful watch policy is assiduously carried out such that disease progression is picked up early and treatment instituted at the appropriate time. The reason for this is that the usual types of chemotherapy for this disease are not curative and the life prolonging properties of chemotherapy are as useful at a time when the patient is symptomatic as early in the course of the disease (see below).


The choice of drug therapy in myeloma is based on the patient's age, performance status and renal function - all of which influence the decision as to whether the patient is suitable for autologous stem cell therapy; a procedure that follows very high dose chemotherapy, itself used as apart of curative chemotherapy in appropriate patients. Where such high dose chemotherapy will never be utilised (e.g. due to old age and frailty) then simple chemotherapy with alkylating agents such as melphalan, coupled with steroids or thalidomide is often used first but in patients who will later be harvested of their blood/marrow stem cells for the high dose procedure, the doctor will try to avoid alkylating agent chemotherapy. Thalidomide (or one of its derivative drugs e.g. lenalidomide), coupled with steroids or other agents is commonly utilised. Particular care is needed when the patient has presented in renal failure, first reversing the factors that are conspiring to worsen the renal condition (e.g. high uric acid, calcium,dehydration, infection etc).


Chemotherapy is usually continued until the patient has achieved a 'plateau' phase (this is when the immunoglobulin marker has achieved a partial remission and remained at this level for 3 months). Following this maximal response to therapy the patient either proceeds to high dose chemotherapy plus the autograft (nowadays with peripheral blood stem cells) or a careful watch policy. The former is the more aggressive approach and reserved for those who are fit enough to withstand the procedure (the potential advantage of which is the hope of eradication of the disease).  In patients who have disappearance of their serum immunoglobulin marker following this procedure, there is a real hope of long disease-free life. In other patients, there follows a period of watchful waiting, until the marker rises or some other event (e.g. bone fracture due to local progression) prompts further therapy. At this time, the patient is treated again, perhaps with the same therapy if first remission was lengthy, or alternative drugs (combinations of active cytotoxic drugs or immuno-modulatory drugs such as thalidomide or bortezomib) will be brought into the therapy. Steroids are also useful.


In this context, the use of bisphosphonate therapy should be discussed. The bisphosphonates are an interesting group of compounds, which attach to bone and make it less likely to be broken down by any disease process, particularly here the bony absorption by myeloma. It is now standard practice to give bisphosphonate therapy (either intravenous pamidronate or oral clodronate) in the maintenance period, so long as the renal function is good.


Lastly it should be stated that local radiotherapy has a very important role in the therapy of multiple myeloma in controlling bony pain. The patient, who comes with low back pain or limb pain because of destructive plasmacytoma in the particular bone, will be most quickly out of pain if he receives local radiotherapy to that bone. Radiotherapy has an important and potentially curative role in the therapy of isolated plasmacytoma.


In the photo, the left panel shows a side view of the neck of a patient with myeloma. The bones are so thin that it is hardly possible to make out the cervical vertebrae and one of them has crush fractured. In the right panel we see the same side view of the cervical spine after therapy. Firstly, the bones are now stronger (more radio-opaque and hence more visible on the x-ray), this is due to drug therapy and local radiotherapy to the neck/cervical spine and secondly a spinal stabilisation operation has been performed and we can see the metal stabiliser in situ.


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