Multiple Myeloma / Plasmocytoma - Causes, Symptoms and Therapy

Multiple myeloma and plasmocytoma: cancer of plasma cells

Multiple myeloma, also called Kahler's disease, is a malignant tumor disease that results from the degeneration of a single plasma cell. Their clones spread in the bone marrow, which is why the disease is also referred to as bone marrow cancer. The individual characteristics are very different, whereby the occurrence of only a single tumor represents the special form of the Plasmozytoms. Advancing medical knowledge has led to a variety of new treatment options and improved prognosis. Nevertheless, the disease is considered incurable.

contents

• Multiple myeloma and plasmocytoma: cancer of plasma cells
• A short overview
• definition
• symptoms
• causes
• diagnosis
• treatment
• Naturopathic treatment
• Current state of research

A short overview

The following overview summarizes the most important facts about the complex clinical picture of multiple myeloma or plasmocytoma. The following article also provides detailed and up-to-date information about the disease.

• definition: Multiple myeloma or a plasmocytoma is a malignant cancer of the group of low-grade non-Hodgkin's lymphomas. Starting from a single degenerate plasma cell, there is an uncontrolled proliferation of these cells, which infiltrate the bone marrow. Typical are many tumor foci, which spread in different places. Rarely, only a single tumor grows, then it is called a plasmocytoma.
• symptoms: Complaints do not always occur (at the onset of illness). Frequently, non-specific general symptoms such as bone pain, fever, weight loss or night sweats first appear. As a result of the diseased plasma cells, typical symptoms of anemia, increased susceptibility to infection, foaming urine (Bence-Jones proteinuria) and unusual bleeding often occur. More serious consequences and complications are possible.
• causes: The causes of the disease are unknown. There is a certain hereditary component, but also the body's own processes and potentially damaging environmental influences play a role in the development of cancer.
• diagnosis: Not infrequently it comes due to a lack or unspecific symptoms to chance findings in blood and urine tests. However, special diagnostic procedures are necessary to make a precise diagnosis. This includes accurate detection of light chain proteins in serum and urine, bone marrow biopsy, and diagnostic imaging.
• treatment: The disease is considered incurable, but medical advances have greatly improved prognosis and treatment options. Today's treatment concepts basically provide chemotherapy including so-called "new substances", high-dose therapies with stem cell transplantation and radiation.
• Naturopathic treatment: Alternative therapies offer many possibilities of supportive cancer therapy, in which the psyche and defenses are strengthened, metabolic processes are regulated and concomitants are diminished. Mistletoe therapy is used to improve the tolerability of chemotherapies.
• Current state of research: The clinical picture of multiple myeloma is the focus of many research activities. In particular, the developments in recent years give those affected by new drugs hope for better treatment options and prognoses.

Multiple myeloma causes an uncontrolled proliferation of degenerate plasma cells in the bone marrow. (Image: Giovanni Cancemi / fotolia.com)

definition

Multiple myeloma or plasmocytoma is a malignant cancer of the group of low-grade non-Hodgkin's lymphomas (malignant diseases of the lymphatic system). Affected here are the B lymphocytes, which belong to the cell group of leukocytes (white blood cells), or resulting from further cell differentiation plasma cells. Low grade (indolent) lymphomas are chronic in nature and grow relatively slowly. As a rule, the disease is not curable, but treatable.

Starting from a single degenerated plasma cell (myeloma cell) in the bone marrow, uncontrolled proliferations of identical plasma cells (clones) occur. These produce steadily monoclonal, unserviceable immune bodies (immunoglobulins), which are also known by the term "paraproteins". This leads to a weakened immune system and healthy blood-forming cells can be displaced in the bone marrow. Further possible consequences are anemia, reduction of platelets and increased bone loss (osteolysis).

The disease is rather rare, but is one of the most common bone and bone cancer in the western industrial nations. Most diagnoses are made in older age (70 years) and men carry a higher disease risk (3: 2). The increasing rate of diagnosis in recent decades is attributed to various factors.

Myeloma cells in the bone marrow affect the blood formation and the vital functions of the individual blood components. (Image: xtaska / fotolia.com)

history

The first description of the disease goes back to the English physicians William Macintyre (1792-1857) and Henry Bence Jones (1813-1873), who examined the first known patient case of Thomas Alexander McBean. For the first time, Bence Jones was able to detect unusual proteins in the patient's urine, which are now known as Bence-Jones proteins. If nowadays a finding of these so-called light-chain proteins (Bence-Jones proteinuria), this points to a malignant multiplication of B lymphocytes and thus often to a multiple myeloma.

In 1873, the Russian surgeon Dr. J. von Rustizky the concept of multiple myeloma and thus describes the presence of multiple plasma cell lesions in the bone. Furthermore, very similar symptoms have been described by other physicians, some of whose names stand for synonymous names of the same disease. For example, in 1889 the Austrian internist Otto Kahler published a detailed clinical description of multiple myeloma under the name "Kahler's disease". Huppert, Bozzolo, Ramón and Cajal, Wright and Weber also made a name for themselves by early investigations into the symptoms of this disease.

Synonyms and terminology

The terms multiple myeloma and plasmocytoma are often used interchangeably but refer to two different clinical pictures. Based on the degeneration of a single plasma cell, their clones multiply and spread in the bone marrow. Typical are many tumor foci that spread diffusely (multiple myeloma). On the other hand, if there is only one focal area, it is the special and rare form of the so-called (solitary) plasmocytoma. Other less common synonyms include Kahler's disease (Kahler's disease) after Otto Kahler and Huppert's disease after Karl Hugo Huppert.

Distinguish from the clinical picture of multiple myeloma are preclinical conditions, such as so-called asymptomatic (smoldering) multiple myeloma and monoclonal gammopathy of unclear significance, which is a benign condition. Relatively large overlaps exist also with the Lymphoplasmozytischem lymphoma, which underlies the Waldenström macroglobulinemia (Morbus Waldenström).

Pathological changes in B lymphocytes and plasma cells can cause different diseases. A multiple myeloma with a single tumor focus is a plasmocytoma. (Image: fancytapis / fotolia.com)

symptoms

Often the first complaints are rather unspecific and varied. Not infrequently, sufferers are initially symptom-free and at the time of diagnosis. General symptoms, which may even occur in the early stages of the disease, mainly include bone pain (back, ribs, hips, extremities) and the so-called B symptoms fever, weight loss and night sweats.

The bone pain is usually caused by the infestation and the increasing spread of the tumor cells, caused by nerve irritation and the pressure on surrounding nerves. Even (small) spontaneous fractures, which can be caused by a dissolution of the bone substance (osteolysis), cause pain.

The infiltration of the bone marrow and the excessive production of the monoclonal plasma cells and paraproteins may cause further discomfort in the course of the disease. For a multiple myeloma characteristic signs are the following:

• Symptoms of anemia such as chronic fatigue, shortness of breath during exercise, headache, irritability and paleness.
• An increased susceptibility to infections (especially urinary tract infections), due to the lack of healthy white blood cells (leukopenia) and functional antibodies.
• A foaming urine, as a sign of Bence-Jones proteinuria and the increased excretion of light chain proteins.
• Unusual bleeding (nosebleeds, heavy menstrual bleeding) and a tendency to blue spots (hematoma) due to disorders in blood formation (lack of platelets).

Unspecific bone pain may be a first sign of bone marrow cancer. (Image: Vasyl / fotolia.com)

In the advanced stage of the disease, the function of the kidneys may be impaired by the amount of proteins produced and the calcium excessively released during osteolysis (hypercalcaemia).

Among the rather rare complications is the hyperviscosity syndrome, whereby the fluidity of the blood is reduced by the high protein content so that it can cause dizziness, angina, thrombosis or other serious consequences. When the light-chain proteins bind to other proteins, amyloid proteins can form, which in rare cases can cause myeloma-associated AL amyloidosis (light chain amyloidosis). Deposits of proteins in various tissues and organs (especially the kidneys, heart, gastrointestinal tract, liver and nerves) can severely impair their function.

causes

The causes are still largely unknown, not least because multiple myeloma has very heterogeneous genetic and clinical characteristics. A variety of different chromosomal abnormalities discovered so far in the context of the disease appear to significantly affect the course of the disease. There is a certain hereditary component, but it is not a hereditary disease.

In the development and spread of multiple myeloma, the body's own processes such as the growth and differentiation of cells, interactions of cells and the immune system play a crucial role.

In addition, it is being discussed whether various harmful and potentially carcinogenic environmental factors, such as radiation or pesticides, favor the development of multiple myeloma.

diagnosis

Often, several months pass between the first symptoms of the disease and the diagnosis. In about 20 percent of those affected also incidental findings of blood and urine tests to determine the disease. For example, a very high rate of erythrocyte sedimentation or a high level of protein in the blood or urine are the first indications of the presence of multiple myeloma. Sufferers of bone pain may also be a possible indication. In any case, in addition to a detailed history and physical examination special diagnostic procedures must be performed.

The detection of light chain proteins in the blood serum and urine provides an important disease information and often leads to a chance finding. (Image: Elnur / fotolia.com)

Laboratory tests of blood and urine samples

After a large blood picture, protein electrophoresis of the serum and urine serves as the first screening method for the detection of a monoclonal protein. Further tests are followed by the precise determination of the type of protein (immuno-fixation electrophoresis) and the measurement of free light chains in the serum. The urine (24-hour urine collection) should always be examined, since the light chain proteins are excreted with intact kidney function and are thus undetectable in the serum. Important in the diagnosis is the precise distinction between the precursors and forms of multiple myeloma.

Bone marrow examination

An important part of further diagnostics is a bone marrow biopsy. As a rule, a sample of the bone marrow is obtained from the posterior iliac crest, which is subsequently used for histological examinations. In this case, the altered cancer cells can be detected, as well as infiltration patterns (diffuse or nodular) and the degree of infiltration.

Radiological examinations

Imaging procedures are used in the initial diagnosis as well as in investigations of the course of the disease. First, conventional radiographs are taken, with the pathological involvement of multiple myeloma predominantly visible on the skull and spine. The radiographs then show typical honeycomb and egg-shaped osteolysis. A finding of multiple osteolyses in the cranial vault, also called shotgun skulls. If the picture of osteoporosis shows, it is a diffuse infiltration. The latter is radiologically indistinguishable from age-related osteoporosis.

Computed tomography is also used in order to be able to detect, above all, low pronounced bone resolutions. Magnetic resonance imaging is mainly used for the evaluation of tumors in the area of ​​the spine and outside the bone (extraosseous).

The radiograph shows typical osteolyses and other kinds of bone damage. (Image: RFBSIP / fotolia.com)

One speaks of a (symptomatic) multiple myeloma in the true sense only if more than 10 percent of monoclonal plasma cells were found in the bone marrow and according to the so-called CRAB criteria of the International Myeloma Working Group (IMWG) at least one secondary organ damage, or a proof accordingly extended SLiM criteria. The CRAB criteria include hypercalcaemia, renal insufficiency, anemia and bone dissolution, while the SLiM criteria relate to the ratio of light chain proteins as well as the amount of plasma cells in the bone marrow and their apparent accumulation in magnetic resonance imaging.

The most important criteria for a plasmocytoma are the detection of less than ten percent monoclonal plasma cells in the bone marrow and a single radiologically detectable disease focus, with a simultaneous lack of altered protein in the blood serum and urine.

treatment

Previously, the need for therapy after the staging of Durie and Salmon was determined. According to recent medical findings, the necessity of an (immediate) therapy after the diagnosis is determined by means of the criteria of the IMWG.

The disease is considered incurable, but in recent years, great medical advances have greatly improved prognosis and treatment options. Aim of every treatment is the stabilization of the patients, the alleviation of the symptoms and a prolongation of life by a possible long-lasting remission (pushing back the illness).

Today, different methods and substances are available for the treatment. Depending on the patient case, it is decided individually which therapeutic measures are appropriate. The age, the general state of health, the expression of corresponding complaints and various risk factors are taken into account in the decision-making.

Possible treatment concepts basically include chemotherapy including so-called "new substances", high-dose therapies with stem cell transplantation and radiation.

Most sufferers receive chemotherapy, often supplemented with the addition of new substances and other forms of therapy (stem cell therapy). (Image: RFBSIP / fotolia.com)

The chemotherapies are intended to kill myeloma cells and thus to suppress the disease throughout the body (systemically). Certain cytostatic drugs, so-called alkylating agents (for example melphalan), have proved to be particularly effective. By a very high dosage of the chemotherapeutic agents a complete remission could already be achieved in relatively many cases. However, side effects can be expected with any chemotherapy and high dose therapy usually leads to severe bone marrow impairment. To counteract this injury, high dose chemotherapy is often combined with the administration of growth factors or stem cell transplantation. For this, the body's own cells (autologous) or stem cells from a donor (allogeneic) come into question.

In principle, irradiation can only be performed on certain body regions (local). With the help of radiation degenerate cells lose their ability to divide to stop tumor growth. Radiation therapy is used primarily for the treatment of bone pain.

Newer substances may be used under certain conditions either in combination with other therapies or as an alternative treatment. These drugs include so-called immune modulating substances (thalidomide, pomalidomide, lenalidomide), proteasome and histone deacetylase inhibitors (bortezomib and panobinostat) and the antibodies elotuzumab and daratumumab. Furthermore, interferon and bisphosphonates are also used. Not all novel drugs have been tested sufficiently for their effect and therefore not yet officially approved.

The treatment of concomitant symptoms may be important in therapy and must be individually clarified with the attending physicians.

Naturopathic treatment

Strengthening the body's own self-healing powers can positively influence the course of the disease and reduce the side effects of chemotherapy. Numerous methods from the field of naturopathy can be used.

In a concomitant biological cancer therapy, various procedures and natural remedies are combined to achieve a strengthening of the psyche and the body, a regulation of the metabolism and an activation of the defense. Mistletoe therapy in particular has been proven to improve the body's resistance and general quality of life, as well as the specific reduction of fatigue, nausea and depressive moods (side effects of chemotherapy). In addition, an additional naturopathic treatment for infection control, for example by means of microbiological therapies, be considered.

The list of all possible natural remedies for the supportive treatment of cancer, even in the case of a multiple myeloma or a plasmocytoma, is long and should be discussed in individual cases with expert experts.

A surprising therapeutic success could previously be attributed to the ginger plant turmeric (turmeric). In the Far Eastern medicine, the active ingredient curcumin from the plant turmeric (Curcuma longa) for a long time as antioxidant, antiseptic and anti-inflammatory. In general, turmeric is healthy and often curative. This has been confirmed by many scientific studies. Now, according to a case report published in April 2017 in the British Medical Journal, the drug curcumin is said to have great potential for remission of multiple myeloma.

Natural remedies can help with cancer therapy. New hope in a multiple myeloma is put into the action of turmeric (curcumin). (Image: Madeleine Steinbach / fotolia.com)

Current state of research

The clinical picture of multiple myeloma is the subject of much international research. There are also several study groups and competence networks in Germany, which are driving research on new forms of therapy and diagnostic procedures and enabling basic research. Thus, especially in recent years, the prognosis of those affected has been significantly improved by new drugs and treatment options.

Researchers have recently made a breakthrough that leaves a message of hope for sufferers: drug kills cancer cells without side effects. As the Pharmazeutische Zeitung reported, a gradual (complete) approval of new drugs is expected in the coming years. (jvs, cs; Updated on 14/01/2019)

Further specialist information:
German Cancer Society - Multiple Myeloma
Myeloma Germany e.V.
Working Group Multiple Myeloma
Myeloma Group Rhine-Main
Guideline Multiple Myeloma