Multiple myeloma is a mclassant blood disease that affects plasma cells. These cells are a specialized form of blood cells that produce immunoglobulin (protein) to help fight infection.
Multiple myeloma develops when these plasma cells grow out of control. The pathological proliferation of plasma cells infiltrates in the bone marrow and in some cases in other organs. Population of myeloma cells can affect the bone tissue causing pain and in some cases spontaneous fracture called pathologic fracture.
Cancerous plasma cells crowd out normal plasma cells and thereby impair their functions. As the number of myeloma cells increases, fewer red blood cells, white blood cells, and platelets (playing an important role in blood clotting) are made. Additionally, as the number of the normal plasma cells helping the organism to fight infections is decreased, the resistence to infections is lowered. The immune deficiency in people with multiple myeloma increases their risk of infections.
Multiple myeloma is often found in elderly people, most often in people older than 60 years of age. Rarely, the disease strikes people younger than 40 years (less than 2 % of all myeloma patients). Multiple myeloma occurs more frequently in man than in woman. It represents approximately 1% of all cancers and, in mclassant blood diseases, it represents 10% of all cases. The incidence of myeloma is 2 - 4 case per 100 000 inhabitants.
Myeloma is not hereditary and not a clear outcome of an increased incidence in close relatives of a myeloma patient was proven. There are, however, very rare families with several cases of multiple myeloma. The significance of this rare phenomenon remains unclear.
The exact cause of multiple myeloma is not known. The research have been evaluating the combination of different influences, factors that are still not precisely defined. Generally, individuals who develop multiple myeloma have no clear risk factors. Myeloma may be the result of several factors acting together. These factors are called risk factors.
As most frequent risk factors are mentioned: some of genetic factors, exposure to radiation and lifelong accumulation of some of the chemical insults.
Myeloma symptoms depend on the stage of the disease.
The main symptoms include bone pain, anemia and symptoms related to renal failure. Bone pain is due to the dissolution of bone tissue by myeloma cells resulting in lytic lesions. In some cases, a spontaneous fracture may therby occur. Anemia (low level of red blood cells) is associated with impaired functions of normal blood stem cells. Insufficient production of red cells causes fatigue and shortness of breath, especially when practicing sports. In some patients, the pathologic protein called light chain protein is present in urine. It may provoke kidney damage; if the damage is severe renal failure may develop. The clinic signs of renal failure include loss of appetite, malaise and decreased urine output. Some patients suffer from frequent infections due to low levels of immunoglobulin.
However, these mentioned symptoms are not necessarily proof of multiple myeloma. The symptoms could be an indication of another illness and that is why an immediate medical care is needed.
Multiple myeloma, diagnosed at an early stage, is less dramatic because the disease can be more effectively treated. Nonetheless, there is no a standard plan of MM detection and people suspecting some risk of developing the disease should discuss the problem they are worrying about with a doctor.
A physical exam and complete medical history are usually the first steps in diagnosing multiple myeloma, the doctors ask about the family medical history, medication history and exposure to risk factors, for example radiations. An overall physical examination assesses the other possible signs of the illness.
Other tests that are commonly used to diagnose multiple myeloma include:
Basic testing (performed in all patients) - x-ray survey, densitometry
Complement testing (not necessarily performed) - CT (Computer Tomography), NMR (Nuclear Magnetic Resonance)
New applications - MIBI (radionuclide scintigraphy), PET (Positron Emission Tomography)
| X-ray | Densitometry | CT | NMR | MIBI | PET | |
| Significance | Lytic lesion, osteoporosis and pathologic fracture detection | Assessment of the density of bone tissues and osteoporosis detection Follow-up of bisphosponate treatment | Non-standard forms of MM, spinal cord or nerve roots compression by metastatic cancer are suspected | Spinal cord or nerve roots compression suspected; bone pain and unclear finding on x-ray survey | Detection and follow-up of myeloma lytic lesions, not revealed on x-ray films | Detection of myeloma lytic lesions not revealed on other imaging tests, detection of another tumour |
| When is it performed | Entrance testing, before transplantation, check-up once per year or as needed | Entrance testing, check-up once a year | Mostly individual | Within 2 days | It is still not clearly defined | Mostly individual |
| Preparation | None | None | 6 h before exam. empty stomach, 1 h before exam Dithiaden 1 tbl., before CT administration of contrast agent | None | During exam, |
no exercising 48 h before exam., no sugar, rice, potatoes, pasta, cheese 24 h before exam. only water 6 h before exam. |
| Examination duration | 20 min | 45 min | 15 min | 1-2 hours | 3-4 hours | 45 min |
| Wait times | Mostly immediate | Immediate | Within 2 weeks, in acute cases immediate | Within 1 month, in acute cases immediate | Mostly immediate | 1 week |
| Results availability | Within 1 day | Within 1week | Within1 - 3 days, in acute cases immediate | Within 1-3 days, in acute cases immediate | Within 1 week | Within 2 days |
| Remark | Comparison with previous films is important | Comparison with previous measures is important | In iodine allergy, it is recommended to be performed in hospital | Metallic implanted device except titanium is contraindication, pacemaker | Comparison with previous findings is important | Comparison with previous films is important |
Many patients with cancer demand a diagnostic assessment by another doctor in such a situation. There are many reasons for providing it, especially if the patient is not satisfied with medical decisions, is the tumour is classified as a rare disease and if there are different treatment options.
There are many ways how to get another assessment.
Every general practitioner should be able to refer to a relevant specialist, such as to a surgeon, clinical oncologist, radiologist-oncologist. These specialists may work in a team or in the scope of oncology centres or programs.
The patient can get contacts to specialists in local health care institution, neighbouring hospital, medicine schools or from other people who are affected with the same type of tumour.
Deciding which therapy to pursue depends upon patient´s overall health and the stage of the disease.
Some of the patients are diagnosed accidentally at the time they have no symptoms. These patients are called asymptomatic patients. Instituting a therapy appears to be justified only when progression of the disease is evident in laboratory, x-ray or other tests. The clinical trials has not shown therapy benefit for asymptomatic patients.
Examinations of paraprotein levels with a median follow-up of 2-6 months are required in asymptomatic patients. Additionally, the progression of the disease has to be monitored with regular x-ray survey and bone marrow biopsies. This medical approach is described as watch-and-wait. As soon as the radiography displays bone affection, the therapy should be instituted immediately.
The treatment of multiple myeloma consists of several modalities often referred to as "complex" therapy. This means the combination of cytostatics (antitumour affects), radiotherapy (radiation therapy), intensive support care (bisphosponates - preserving bone mass; analgesics) and orthopaedic treatment (conservative and surgery). The treatment is predominantly ambulatory, unless the type of therapy demands the hospitalization or complications emerge.
1. Anti-cancer treatment (chemotherapy) - targeted at myeloma cells
2. Supportive care - manages the symptoms but it doesn´t have an effect on myeloma cells.
The goal of anti-cancer treatment is to eliminate or minimize all clinically or laboratory detectable symptoms.
The anti-cancer treatment involves a standard chemotherapy or high-dose chemotherapy with stem cell transplant. The treatment option depends on the patient´s age and overall health condition. Drugs are delivered through intravenous infusion or orally as a pill. Cytostatics may form different combination chemotherapy regimens repeated evenly (mostly with 1 month interval). The overall duration of induction therapy depends on patient´s response. Predominantly, it is administered in 6-8 cycles (6-8 months). During remission phase, the therapy using cytostatics may be replaced by maintenance therapy. The maintenance therapy consists mostly of different immunomodulatory agents or its combinations. When relapse of the disease occurs, a cytotoxic chemotherapy is instituted.
High-dose chemotherapy with stem cell transplant procedure:
This procedure is the most commonly used pattern. It can be, nevertheless, modified according to the response to the treatment and to the actual condition of the patient.
High-dose therapy in conjunction with allogenic stem cell transplant is rarely performed for treatment of myeloma. The stem cells used for the transplant are from a donor whose blood cells closely match the patient´s one. Nevertheless, this type of transplant remains very risky.
Radiotherapy (radiation treatment) is an integral part of myeloma treatment process. Radiotherapy kills off the myeloma cells in the bone and shrinks the cancer. This helps to reduce bone pain. The treatment duration is usually 5 days a week, during one or more weeks.
The goal of supportive care is to improve comfort and quality of life of the patient. Supportive care has no effect on myeloma cells but helps to minimize troublesome symptoms provoked by anti-cancer treatment. These medical approaches may be resumed in two procedures:
Long-term specialized bone treatment by means of bisphosponates. These drugs bind to a bone areas destroyed by myeloma cells, slow down the dissolution of bone mass and reduce pain. After an acute phase of the disease, administrating of vitamin D and calcium together with bisphosponates is recommended to boost its effect.
Medical response is an evaluated (measurable) outcome of the treatment. It is evaluated in regular intervals with common examinations (usually the same as in diagnosing - serum and urine analysis to detect the level of paraprotein, bone marrow analysis, x-ray survey) that permit to check up the symptoms and compare them with the previous results. According to the overall outcome, the medical response may be classified in several categories with precisely defined criteria.
Complete response - CR requires that the patient complies with all three criteria
In patients that comply only with some of the critaria of the complete remission and that meet the bellow-defined conditions, the response is said to be partial.
Partial response - PR requires that the patient complies with all three criteria
In patients that comply only with some of the critaria of partial remission and that meet the bellow-defined conditions, the response is said to be minimal.
Minimal response - MR requires that the patient complies with all three criteria
Patients that have complied with some of the criteria of partial response and meet the criteria of minimal response are classified as patients with minimal medical response.
No change - NC: the disease complies with none of the defined criteria but doesn´t progress.
Plateau: the term plateau is used for the phase of the disease where the concentrations of immunoglobulin remain stable or vary not more than by 25% for a minimum of 3 months.
Medical response to transplantation
Relapse (occurs when a person is affected again by symptoms of a disease that affected them in the past)
Relapse after complete response requires that the patient complies with at least one criterion
Progressive disease: this term is used to determine the condition where the complete response was not achieved. At least one criterion is than met:
Clinical trials are research studies involving new anti-cancer drugs. Physicians investigate clinical outcomes to assess the efficacy of a new treatment and its side effects. If a clinical trial results appear promising, they are compared with the most widely used treatment to state whether the new treatment is more efficient or has less side effects. Patients that participate in clinical trials may benefit from state-of-the-art treatment methods before they are authorized by the relevant national institutions. Furthermore, participation in clinical trial can help understand mclassant diseases and, thereby, help yourself and future patients.
Oncology research gives people hope. Physicians and researchers worldwide are now given further information about the causes of multiple myeloma and they investigate the ways how to prevent this disease. At the same time, the trials evaluating detection alternatives are carried out.
Ongoing trials are testing high-dose chemotherapy with stem cell transplant targeted at gain in life expectancy. This treatment option is considered to be the most effective but the most demanding.
The growing interest in so-called immunomodulatory drugs having the ability to influence immune response in organism and inhibit angiogenesis (an important process for cancer cell growth) has now opened the field for research. These drugs are a form of biological treatment and their mechanism of action is different from classical chemotherapy. Its precise indication in the treatment of multiple myeloma is being evaluated. This class of novel drugs involves thalidomide, bortezomib (Velcade), Revlimid and Actimid.
Information about newly formed Patient support group are available on www.mnohocetnymyelom.cz or you can contact us on these e-mail addresses: imareschova@fnbrno.cz, katrin.acil@seznam.cz, r.hajek@fnbrno.cz.
