Brief overview
- Symptoms: pain, especially in the back, anemia with symptoms such as fatigue, pallor, dizziness and difficulty concentrating, foamy urine, weight loss, increased susceptibility to infection, small skin hemorrhages
- Causes and risk factors: Genetic changes in plasma cells are thought to be the cause. Risk factors include environmental influences such as ionizing radiation or certain pollutants, advanced age, a weakened immune system and certain viral infections.
- Diagnosis: Diagnosis is made on the basis of typical symptoms, certain blood and urine values, an examination of the bone marrow and with the aid of imaging procedures.
- Treatment: The standard of care is high-dose chemotherapy followed by stem cell transplantation. If this is not an option, various drugs are available.
- Prevention: Since the cause of the disease is unknown, multiple myeloma and plasmacytoma cannot be specifically prevented.
What is a plasmocytoma?
A plasmocytoma is a special form of blood cancer in which so-called plasma cells multiply uncontrollably in the bone marrow. Other names for plasmocytoma are “Kahler’s disease” and “multiple myeloma”.
In everyday language, many people use the terms multiple myeloma and plasmocytoma synonymously, i.e. synonymously. Strictly speaking, however, they are not. Multiple myeloma refers to a form of disease in which the proliferating, malignant plasma cells are diffusely distributed in the bone marrow or soft tissue.
Plasmocytoma, on the other hand, is a special form of multiple myeloma. In this case, the proliferation of plasma cells occurs only locally. Thus, in plasmocytoma there is only one tumor focus in the entire organism (solitary plasmocytoma), whereas in multiple myeloma there are several.
Red and white blood cells are produced in the bone marrow. While the red blood cells (erythrocytes) are responsible for oxygen transport in the body, the white blood cells (leukocytes) serve the immune defense. There are various subgroups of leukocytes, such as granulocytes, T cells or B cells.
Plasma cells represent the most mature stage of B cells and are responsible for the production of antibodies. These are specialized proteins that are able to neutralize pathogens such as bacteria and viruses. A plasma cell and its daughter cells together form a so-called plasma cell clone. All cells belonging to the clone form a single, specific antibody.
In multiple myeloma, changes in the genetic material (mutation) occur in one of the many plasma cells. The degenerated plasma cell then begins to proliferate uncontrollably. It and all its descendants produce large amounts of a single monoclonal antibody. In some cases, there are only fragments of this antibody, the so-called kappa and lambda light chains. Physicians also refer to these antibodies and antibody fragments as paraproteins.
The antibodies formed by the degenerated plasma cells are usually functionless and do not fulfill their task in the immune defense. As a result, the immune system is weakened in multiple myeloma, making affected individuals much more susceptible to infection. Over time, the degenerate plasma cells crowd out more and more healthy cells in the bone marrow, causing various symptoms.
Frequency of multiple myeloma
What are the symptoms of multiple myeloma?
Whether and to what extent symptoms occur varies from patient to patient. At the beginning, multiple myeloma and plasmacytoma usually do not cause any symptoms. About a quarter of those affected have no symptoms at the time of diagnosis. However, acute courses with pronounced symptoms are also possible.
Bone pain
The first symptoms of multiple myeloma are usually bone pain. Patients particularly often complain of back pain. In addition, the plasma cells produce substances that cause the body to break down more bone tissue (often in the area of the spine). Therefore, the risk of bone fractures is increased in multiple myeloma and plasmacytoma.
Anemia
Increased susceptibility to infections
When the proliferating plasma cells also crowd out the healthy white blood cells, the body is no longer able to produce sufficient intact antibodies. This weakens the immune system, and infections with bacteria or viruses occur more easily.
Altered urine
If the plasma cells in multiple myeloma produce only light chains instead of complete antibodies, the kidneys excrete some of them. Sometimes, however, the so-called Bence-Jones proteins settle in the kidney tissue and damage it. Some affected individuals report foamy urine as a result.
Increased bleeding tendency
The formation of blood platelets (thrombocytes) is also impaired in multiple myeloma. Platelets are normally responsible for blood clotting. As a result of platelet deficiency, bruising and bleeding of the skin and mucous membranes occur more frequently.
General signs of disease
Causes and risk factors
The starting point for a multiple myeloma or plasmacytoma is a degenerate plasma cell that multiplies exponentially. Plasma cells belong to the B-lymphocytes, a subgroup of white blood cells. Their most important task is the production of antibodies. Degenerated plasma cells, on the other hand, produce altered, mostly functionless antibodies (paraproteins).
The cause of the degeneration of plasma cells is changes in the genetic material. It is not yet fully understood why this occurs. However, there are certain risk factors that are suspected of promoting multiple myeloma. These include, for example:
- Environmental factors such as ionizing radiation and certain chemicals and pesticides.
- An older age
- A benign precursor of multiple myeloma, called “monoclonal gammopathy of unknown significance” (MGUS)
- A weakened immune system
- Certain viral infections
Investigations and diagnosis
It is advisable to consult a doctor in the event of any symptoms that may indicate a plasmocytoma or multiple myeloma. The first clues to the disease are already provided to the doctor by typical symptoms such as bone pain, a higher susceptibility to infections, foamy urine or weight loss.
However, many of the symptoms are non-specific and also occur in other diseases. With the help of various examinations, it is possible for the physician to confirm his suspicion and to differentiate multiple myeloma from other clinical pictures.
Blood and urine tests
Checking blood levels is a quick way to get initial indications of multiple myeloma or plasmacytoma. The degenerate antibodies can be detected in the blood by an elevated total protein level. With special tests, the characteristic monoclonal antibodies can also be detected directly.
If bone is affected, elevated calcium levels are found in the blood count: bone consists largely of calcium. If multiple myeloma accelerates bone resorption, the released calcium is distributed in the blood and can be measured.
Bone marrow aspiration
If multiple myeloma or plasmocytoma is suspected, the physician performs a bone marrow puncture. Under local anesthesia, a needle is used to remove bone marrow from a suitable bone, usually the iliac crest. He then examines the bone marrow sample under the microscope. In healthy individuals, the proportion of plasma cells is usually no more than five percent. People with multiple myeloma, on the other hand, often have higher levels.
In addition, after a bone marrow puncture, it is possible to examine the degenerated cells for certain chromosomal changes. This is important because the type of mutation influences the course of the disease.
Imaging procedures
Computed tomography (CT) and magnetic resonance imaging (MRI) are additional imaging examination methods used in multiple myeloma. They are more sensitive and allow even more precise identification of the extent to which the skeletal system has already been affected by the multiple myeloma or plasmacytoma. They can also be used to detect tumor sites outside the bone marrow.
Disease stages
If the physician determines during the examinations that multiple myeloma or plasmacytoma is present, it is important to determine the stage of the disease. In multiple myeloma and plasmacytoma, doctors distinguish between three stages. Which stage an affected person is in depends on the level of certain blood values and whether a high-risk mutation is present. In general, the lower the stage, the less advanced the tumor and the better the prognosis.
Treatment
Multiple myeloma and plasmocytoma are still not considered curable. However, it is now possible to achieve long disease-free periods thanks to improved treatment options. The goal of therapy is to prolong life, quickly alleviate symptoms, and avoid complications.
Is it always necessary to treat multiple myeloma?
In multiple myeloma or plasmocytoma, therapy is not necessary in all cases. Especially in people who do not yet have any symptoms, it is initially sufficient to examine them closely and monitor the course of the disease. Experts refer to this strategy as “watch and wait”.
- Elevated blood calcium levels
- Impaired kidney function (renal insufficiency)
- Anemia
- Bone lesions
- A proportion of at least 60 percent clonal plasma cells in the bone marrow
- An altered ratio of kappa and lambda light chains in the blood
- More than one tumor focus greater than five millimeters in size on MRI
In addition to the SLiM-CRAB criteria, other reasons for therapy in some cases include:
- Pain
- Fever, night sweats and weight loss (the so-called B-symptomatology)
- Recurrent severe infections
- Altered blood flow characteristics, for example due to increased protein content
In addition, the doctor considers how high the risk is that the symptoms and organ functions will worsen without treatment.
Chemotherapy and stem cell transplantation
However, high-dose chemotherapy is very aggressive. It kills not only the tumor cells, but also all blood-forming cells. After high-dose chemotherapy, the body is therefore no longer able to produce blood cells: neither the red blood cells necessary for oxygen transport nor the white blood cells essential for immune defense.
This is why a so-called autologous stem cell transplantation is required: the patient receives his or her own stem cells, which were obtained from the patient’s blood before the chemotherapy. They colonize the bone marrow and ensure that the formation of immune and blood cells is restarted.
Therapy with other drugs
Not everyone with multiple myeloma can undergo the burdensome high-dose chemotherapy followed by stem cell transplantation. In addition, this combined treatment does not work for all sufferers, so relapses do occur. In this case, treatment usually involves the use of drugs. These belong to different drug classes.
- Cytostatic drugs such as melphalan or bendamustine inhibit the growth of tumor cells.
- High-dose glucocorticoids (dexamethasone, prednisolone) sometimes cause a rapid reduction in tumor mass.
- Proteasome inhibitors (PI) such as bortezomib and carfilzomib inhibit the so-called proteasome, an enzyme complex that is important for the breakdown of proteins. If the proteasome is blocked, old, functionless proteins accumulate in the cells. This is associated with great stress and leads to the death of the cancer cells.
- Histone deacetylase inhibitors affect the activity of genes important for tumorigenesis and tumor cell survival.
Various biotechnologically produced therapeutic antibodies are also used in multiple myeloma. They bind to certain structures on the surface of the cancer cells. On the one hand, this makes it easier for the immune system to recognize and destroy the cancer cells. On the other hand, the antibodies initiate a chain of reactions inside the tumor cell that ultimately kills the cell.
The available active ingredients are often used in combination with each other. The physician decides which combination of active ingredients is best for each individual patient.
Radiation therapy
- Osteolyses that increase the risk of bone fracture
- Tumor foci located outside the bone marrow
- Pain in the skeleton
Supportive therapy
Especially if the bone is affected, multiple myeloma or plasmacytoma is sometimes extremely painful. Effective painkillers are usually used in this case. Sometimes radiation therapy is also suitable in this case. In this case, individual tumor foci are irradiated in order to inhibit cell growth.
In addition, the doctor may prescribe so-called bisphosphonates. These inhibit bone resorption and have a stabilizing effect on the bones. In this way, the number of bone fractures can be reduced and pain alleviated. Since the calcium level in the blood sometimes falls below the normal value during bisphosphonate treatment (hypocalcemia), it may be advisable to take calcium and vitamin D. They reduce the risk of hypocalcemia. They reduce the risk of hypocalcemia.
A special diet is usually not required for multiple myeloma or plasmocytoma. However, there are restrictions after stem cell transplantation, as the body does not protect itself effectively against infections during this time. Therefore, it is helpful for affected individuals to avoid foods that may be highly contaminated with germs. These include, for example:
- Raw and fresh dairy products
- Molded cheese
- Raw meat (for example, ground pork or tartar)
- Raw fish
- Fresh (unheated) fruits and vegetables
- Nuts, almonds, sprouted grains and cereal products
Comprehensive information on suitable and unsuitable foods and the correct preparation can be obtained by affected persons after stem cell transplantation from the specialist staff in the hospital.
Course of the disease and prognosis
Prognosis and life expectancy in multiple myeloma
A complete cure is only possible in very few cases of multiple myeloma and plasmacytoma. However, the prognosis has improved significantly in recent years due to new and effective therapies. As recently as the 1980s, the average life expectancy for multiple myeloma was only up to two years. Today, patients survive for an average of five to ten years after diagnosis.
However, life expectancy depends largely on the tumor stage. For example, the five-year survival rate in stage 1 with the currently available therapy options is 82 percent. This means that 82 percent of those affected will live for at least five years after diagnosis. In stage 2, it is 62 percent, and in stage 3 it is still 40 percent. In addition to a high tumor stage, advanced age and certain high-risk mutations are considered unfavorable prognostic factors.
End stage and cause of death
In the final stage of multiple myeloma, the tumor cells have already spread very widely. Patients often die because not enough healthy blood cells are produced in the bone marrow. This results in an increased risk of infection. Infections and the resulting complications are considered the most frequent cause of death in multiple myeloma.
Prevention
Since the cause of multiple myeloma or plasmacytoma is not known, the disease cannot be specifically prevented. There is also no special program for the early detection of multiple myeloma. Therefore, the disease often comes to light rather by chance during an examination that was performed for other reasons.
