I The basics of multiple myeloma
1.What is multiple myeloma? What is the cause of the disease?
Multiple myeloma is a malignant proliferative tumor that originates from plasma cells in the blood system. Myeloma cells clonally proliferate in the bone marrow, causing osteolytic bone destruction; at the same time, myeloma cells secrete large amounts of monoclonal immunoglobulins, and excessive immunoglobulin light chains are excreted in the urine, which is called periproteinuria, and the large amount of monoclonal immunoglobulins inhibits the synthesis of normal polyclonal immunoglobulins, which easily causes infection. It is often accompanied by anemia, renal impairment and extramedullary plasmacytoma. Huang Zhongxia, Department of Hematology and Oncology, West Hospital, Beijing Chaoyang Hospital, Capital Medical University
The exact pathogenesis of myeloma is still unclear, but with the development of various biotechnologies, the understanding of the pathogenesis of myeloma has advanced. The pathogenesis of myeloma may be related to chromosomal abnormalities caused by gene mutations.
2. Is multiple myeloma contagious?
Although certain genetic abnormalities have been found in some myeloma patients, most of these abnormalities are acquired by mutations, so they are generally not contagious to others or their offspring.
3.What are the types of multiple myeloma? How are they differentiated?
According to the different monoclonal immunoglobulins secreted by multiple myeloma cells, multiple myeloma can be divided into the following 8 types: IgG, IgD, IgA, IgE, IgM, light chain, biclonal and non-secreting. IgG, IgA, light chain and IgD types are more common.
4.Is multiple myeloma fatal? How long can I live if I have it?
Multiple myeloma is still an incurable disease, but since autologous stem cell transplantation has been successfully applied to multiple myeloma patients, the efficacy and survival have been greatly improved. The successful use of immunomodulatory drugs, especially proteasome inhibitors in the 21st century, in myeloma patients since the late 1990s has significantly improved overall long-term survival.
Multiple myeloma is a heterogeneous disease and the response to treatment, the occurrence of complications and survival vary greatly from patient to patient. Survival is highly variable, from a few months in short cases to more than 10 years in long cases.
5.Who is prone to multiple myeloma?
The incidence rate of multiple myeloma in China is about 1/100,000, which is lower than that in western industrialized countries (about 4/100,000), and the age of onset is mostly between 50-60 years old, and those under 40 years old are less common.
Therefore, older people, especially those with a family history of tumor or tumor susceptibility factors (such as special occupations), are relatively more likely to develop multiple myeloma.
6. Do specific occupations cause multiple myeloma?
Ionizing radiation has been shown to be a risk factor for acute myeloid leukemia, but there is no evidence of a role for chronic low-dose radiation exposure in the development of multiple myeloma. With modern industrial protection and strict regulations, occupational radiation exposure is unlikely to significantly increase the incidence of multiple myeloma. Moderated studies of organic solvents, herbicides, and other chemical agents have also failed to find a role in the development of myeloma.
7. Pathogenesis of multiple myeloma
The diverse clinical manifestations of MM are caused by the uncontrolled proliferation and infiltration of malignant clonal plasma cells and their secretion of large amounts of monoclonal immunoglobulins: overproliferation of tumor cells in the bone marrow at the primary site, leading to suppression of bone marrow hematopoietic function; extensive infiltration of tumor cells may involve lymph nodes, spleen, liver, respiratory tract and other parts of the body, causing dysfunction of the affected tissues and organs: some factors secreted by tumor cells The presence of a large amount of monoclonal immunoglobulin secreted by tumor cells in the blood causes increased blood viscosity and dysfunction of coagulation factors, while the excretion of excessive light chains from the kidneys causes kidney damage and the deposition of light chains in tissues and organs causes amyloidosis damage, while the proliferation of normal polyclonal plasma cells and the synthesis of polyclonal immunoglobulin are inhibited, making the body less immune and susceptible to secondary infections.
Examination/diagnosis of multiple myeloma
1. How to diagnose multiple myeloma
The diagnosis should be made by combining the percentage of myeloma cells in bone marrow smear examination, the amount of M protein in blood or urine, osteolytic damage in X-ray examination and other indicators with the clinical manifestations of patients.
Generally, the diagnosis of multiple myeloma should be considered when there is an increase of plasma cells in bone marrow (>30%), the amount of M protein in blood or urine is greater than 35g/L or 1g/24h respectively, and there is osteolytic damage on X-ray.
2.Clinical staging criteria of multiple myeloma
The clinical stage reflects the early and late course of the disease, and the early and late course of MM mainly depends on the total number of myeloma cells in the patient’s body (tumor load), when the number of tumor cells is limited, it does not cause clinical symptoms, and the patient may not notice it, which is called the pre-clinical stage, and this stage is usually 1 to 2 years, and the pre-clinical stage of a few cases can be 4 to 5 years or longer. When the total number of tumor cells is ≥1×1011, the clinical symptoms will begin to appear, and the disease will gradually worsen as the number of tumor cells increases.
3.Pathological typing of multiple myeloma
(1) IgG type: The most common type, accounting for about 50% of MM, with typical clinical manifestations of MM
(2) IgA type: IgA type accounts for about 15%-20% of MM, in addition to the general manifestations of MM, IgA easily aggregates into multimers and causes hyperviscosity, and is prone to hypercalcemia and hypercholesterolemia, etc.
(3) Light chain type: Its monoclonal immunoglobulin is monoclonal to κ chain or monoclonal to λ chain, while heavy chain is absent, this type accounts for about 15%-20% of MM, this type of tumor cells are often poorly differentiated, proliferate rapidly, bone destruction is common, and renal function damage is more severe.
(4) IgD type: It accounts for about 8% to 10% of MM. In addition to the general manifestations of MM, it is characterized by relatively young age of onset, extramedullary infiltration, and relatively frequent osteosclerotic lesions.
(5) IgM type: rare, accounting for only about 1% of MM, in addition to the general clinical manifestations of MM, because of its larger molecular weight (molecular weight 950000) and easy to form pentamers and increase blood viscosity, so prone to high viscosity syndrome is its characteristics.
(6) IgE type:, this type is rare
(7) biclonal or polyclonal type: this type is rare, accounting for less than 1% of MM
(8) non-secretory type: this type accounts for about 1% of MM, patients have significant proliferation of plasma (tumor) cells in the bone marrow, bone pain, bone destruction, anemia, reduced normal immunoglobulin, prone to infection and other typical clinical manifestations of MM, but no M component in the serum, no monoclonal light chain in the urine (urine this – week protein negative).
4.Differential diagnosis of multiple myeloma
The misdiagnosis rate of this disease is very high. Patients may be misdiagnosed as respiratory infection, nephritis, bone disease and delayed because of fever, urine change, back and leg pain. In elderly patients with renal damage along with skeletal pain or anemia that does not parallel renal insufficiency (renal anemia parallels the degree of renal insufficiency), tests for myeloma should be performed. Low back pain is one of the main symptoms of multiple myeloma and is often one of the main complaints of patients seeking medical attention, who may choose general surgery, orthopedic consultation. It is often misdiagnosed as lumbar strain, lumbar spine tuberculosis, osteoporosis and other diseases, which should be distinguished from reactive plasmacytosis, monoclonal immunoglobulinemia of undetermined significance (MGUS) and other M-protein producing diseases such as chronic infection, chronic liver disease and autoimmune diseases.
5.X-ray examination of multiple myeloma
X-ray examination is of great significance in the diagnosis of this disease. The following four types of X-ray manifestations of this disease can be seen: (1) diffuse osteoporosis: vertebrae, ribs, pelvis and skull are often obvious, also seen in the long bones of the limbs; (2) osteolytic lesions: multiple round or ovoid, with clear and sharp edges like chisel-like osteolytic lesions are the typical X-ray signs of this disease. (3) Pathological fracture: most commonly seen in the lower thoracic and upper lumbar vertebrae, mostly as compression fractures, followed by the ribs, clavicle, pelvis, and occasionally the bones of the extremities; (4) Osteosclerosis: this lesion is rare.
Treatment of multiple myeloma
1.The main treatment methods of multiple myeloma
Chemotherapy is the main treatment for this disease, and the application of new chemotherapeutic drugs and the improvement of medication methods are the key factors to improve the efficacy of this disease in recent years. For patients <65 years of age who are proposed for hematopoietic stem cell transplantation, the VD regimen (bortezomib + dexamethasone) is currently the standard induction therapy regimen prior to transplantation. Other bortezomib-based induction chemotherapy regimens PAD (bortezomib + adriamycin + dexamethasone), VDD (bortezomib + liposomal adriamycin + dexamethasone), and VTD (bortezomib + thalidomide + dexamethasone) have also shown good efficacy. Stem cell mobilization collection was performed for those who achieved partial remission or better outcome with 4 courses of induction therapy.
The VAD, TD, PAD, and DVD regimens are recommended for patients >65 years of age who cannot receive stem cell transplantation for reasons such as frailty or their own choice, and for those with blood Cr >176 mmol/L. For patients with blood Cr<176mmol/L, MPT (melphalan + prednisone + thalidomide), MPV (melphalan + prednisone + bortezomib) or MPR (melphalan + prednisone + thalidomide) are recommended as MP plus new drug regimens.
2.Reactivation analogues for multiple myeloma
Reactivation is a non-cytotoxic drug used in the treatment of multiple myeloma in recent years, and has become one of the important therapeutic drugs for myeloma. Its anti-tumor mechanism is not fully understood, but mainly includes the following aspects: 1 Inhibits angiogenesis 2 May directly inhibit the growth of myeloma cells and bone marrow stromal cells 3 Alters adhesion factors and thus impairs the adhesion molecules of myeloma cells to stromal cells 4 Further affects the relationship between tumor microenvironment by inhibiting cytokines such as IL-6 and TNF-α 5 Stimulate T lymphocytes (mainly CD8+ cells) to regulate the immune system.
3. Issues to be noted in the treatment of multiple myeloma
(1) Asymptomatic myeloma or D-S stage 1 patients can be observed and reviewed every three months.
(2) Patients with symptomatic myeloma or myeloma without symptoms but with myeloma-related sexual organ failure should be treated early.
3）.Age <65 years old, suitable for autologous stem cell transplantation, and avoid alkylating agents and nitrosoureas.
(4) Those who are suitable for clinical trials should be considered for entry into clinical trials.
4.Common treatment prescriptions for multiple myeloma
(1) Treatment Supportive therapy plays an important role in the treatment of this disease and should not be neglected.
（The application of new chemotherapeutic drugs and the improvement of medication methods are the key factors to improve the efficacy of this disease in recent years.
(3) Radiation therapy Radiation therapy is suitable for the treatment of isolated bone plasmacytoma and extramedullary plasmacytoma that are not suitable for surgical resection, and is also an effective treatment to reduce severe local bone pain.
(4) Surgery When osteolytic lesions occur in the thoracic or lumbar spine, making the patient bedridden and possibly leading to paraplegia due to compression fractures, resection of the diseased vertebra and artificial vertebral body replacement and fixation can be performed.
(5) Hematopoietic stem cell transplantation Although chemotherapy has achieved remarkable efficacy in this disease, it has failed to cure the disease. At present, allogeneic hematopoietic stem cell transplantation is the only effective means to cure multiple myeloma.
5.Cautions for chemotherapy of multiple myeloma
1. Gastrointestinal reaction is the most common symptom. Most chemotherapeutic drugs will cause varying degrees of nausea, vomiting and poor nutrition, and some will cause abdominal pain, diarrhea and even intestinal mucosal necrosis and perforation. Therefore, give high-calorie, high-protein, high-vitamin, light and easy-to-digest diet as the principle. Those who vomit intensely should be instructed to increase the amount of oral fluid, and if necessary, intravenous rehydration.
2.Observation of chemotherapy drug rehydration: attention should be paid to the protection of blood vessels, drug extravasation is strictly prohibited, and 0.9% NS is used to flush the tube before each drip, and NS is also needed to flush the tube after use.
3, bone marrow suppression is the most serious adverse reactions, should closely observe the patient’s skin, oral cavity, gums, and other bleeding points, but also observe the color and amount of urine and stool, whether there is bleeding, and monitor the blood routine 2 times a week (according to the patient’s condition).
4, to pay attention to the side effects of drugs, some chemotherapy drugs can cause peripheral neuritis, numbness in the hands and feet, and even cause myocardial and cardiac conduction damage, should be regularly monitored electrocardiogram.
5.Since the side effects of chemotherapy drugs are generally large and can affect the patient’s confidence in treatment, nurses should work together with family members to care for the patients, give them more successful cases or communicate with them from time to time, and keep abreast of the patient’s needs to reduce the patient’s psychological burden and increase their confidence in treatment.
6.The efficacy standard of multiple myeloma
The efficacy criteria of multiple myeloma include 1 strict complete remission (sCR), 2 complete remission (CR), 3 near complete remission (nCR), 4 very good partial remission (VGPR), 5 partial remission (PR), 6 stable disease, progression, 7 relapse after remission, etc.
7. Treatment of refractory multiple myeloma
The treatment of refractory multiple myeloma is complex, and its therapeutic strategies include the development of chemotherapy regimens without cross-resistance to cytotoxic drugs and the search for new drugs that affect the proliferation, apoptosis, microenvironment and signaling pathways of myeloma cells. The former drugs or regimens more successfully used in refractory relapsed myeloma include drugs such as fludarabine and desoxorubicin or regimens composed of them, while the latter include proteasome inhibitors such as bortezomib, which currently represent the new generation of clinical treatment for refractory relapsed myeloma and have led to a new breakthrough in the treatment of myeloma. The most appropriate management plan for refractory relapse must be based on the individual patient’s situation, such as the time of relapse, age, previous treatment, bone marrow functional status and other clinical conditions.
IV Symptoms of multiple myeloma
1 Clinical manifestations of multiple myeloma
The clinical manifestations of multiple myeloma are diverse.
(1) Bone damage is one of the characteristic clinical manifestations of multiple myeloma, manifested as bone pain, osteolytic damage, diffuse osteoporosis or pathological fracture
(2) Anemia and hemorrhagic tendency. Anemia usually occurs slowly and the symptoms of anemia are not obvious, and hemorrhagic tendency is not uncommon, mostly manifested as mucosal oozing and skin purpura.
(3) Infections, respiratory system infections such as pharyngeal and pulmonary infections are common
(4) Renal damage, half of the patients have proteinuria, hematuria, and tubular urine at an early stage
(5) Hyperviscosity syndrome, manifested as headache, dizziness, tinnitus, blurred eyes, visual impairment, skin purpura, nasal bleeding, numbness of hands and feet, and ulcers in the lower limbs that do not heal easily, etc.
2.Early symptoms of multiple myeloma
Bone pain is often the early and main symptom, among which lumbosacral pain is the most common, followed by chest pain, pain in limbs and other parts of the body. Early pain is mild and easily misdiagnosed as rheumatism, rheumatoid arthritis, costochondritis, etc. In half of the patients, renal damage, such as hematuria, proteinuria, and tubular urine, occurs early. In addition, respiratory and urinary tract infections are more common.
3.Characteristics of non-secretory multiple myeloma
Nonsecretory Multiple Myeloma (NSMM) is a variant of multiple myeloma. Since the first case of NSMM was reported in 1958, there have been uninterrupted case reports, but overall the disease is still relatively rare, accounting for about 1% to 5% of multiple myeloma. Non-secretory multiple myeloma can be divided into two subtypes: one is a mutation in the gene of immunoglobulin synthesis in tumor cells, which cannot synthesize immunoglobulin, called unformed or non-productive type; the other is a disorder in the secretion function of tumor cells, which can synthesize immunoglobulin but cannot secrete it out of tumor cells, called synthetic but non-secretory or productive type multiple myeloma. The clinical manifestations, treatment and prognosis of both subtypes are the same. However, the renal function is less impaired.
V Diagnostic/treatment misconceptions of multiple myeloma
I. Ways to reduce misdiagnosis of multiple myeloma
Bone pain is the most common symptom of MM. X-ray or CT examination should be performed promptly for such patients, and serum protein electrophoresis and urine M protein and light chain examination should be improved if there is bone destruction. For patients with bone pain accompanied by anemia or recurrent infection and increased erythrocyte sedimentation rate, the possibility of malignant tumor bone metastasis, tuberculosis or MM should be considered. If there are osteolytic lesions or extensive osteoporosis, high concentration of immunoglobulin or monoclonal light chain, and morphologically abnormal plasma cells >15% in bone marrow, and two of the three items are positive, MM can be diagnosed by excluding other diseases.
Why multiple myeloma is easily misdiagnosed
The clinical manifestations of MM are complex and diverse, and patients are often diagnosed with a certain systemic lesion, so clinicians do not know enough about it and neglect the differential diagnosis, and it is easy to be misdiagnosed as a common disease or multiple diseases. Subjective assumptions about pathological fractures, biased thinking, lack of a holistic view of the condition, isolation of a clinical symptom or medical examination, ignoring other manifestations, resulting in misdiagnosis. Misdiagnosis is caused by over-reliance on medical and technical examinations without comprehensive analysis of clinical manifestations. Bone marrow aspiration is decisive for the diagnosis of MM, but some physicians ignore the focal and nodal distribution characteristics of MM bone marrow lesions (especially in the early stage), and are satisfied with the benign results of one or two bone marrow aspirations, and blindly exclude the diagnosis of MM.
Third, nausea and vomiting: it is actually multiple myeloma
Multiple myeloma mainly infiltrates the soft tissues of bone marrow, and it can produce abnormal monoclonal immunoglobulins, causing bone destruction, anemia, renal impairment and abnormal immune function. Its wide variety of clinical first symptoms may be related to the different degrees of maturation of myeloma cells and the time and extent of infiltration into blood, bone marrow and kidney tissues. In a small number of patients, the common clinical manifestations of myeloma may not be seen, and nausea and vomiting may be the first symptoms, which are of course very rare but should not be ignored. Therefore, in clinical practice, bone marrow aspiration should be performed whenever middle-aged or elderly patients with anemia and proteinuria, and sometimes multiple sites should be punctured. This will enable early diagnosis, enable patients to receive timely treatment and improve their prognosis.
D. Beware: physical signals of multiple myeloma
Multiple myeloma often starts with low back pain and generalized bone pain, mainly lumbar spine compression fracture. Renal function impairment and anemia are common clinical symptoms, in addition, various clinical symptoms such as fever, excessive urination, weakness, nausea, vomiting and diarrhea can also be seen. When you feel unwell, you should go to the hospital in time for a preliminary examination to rule out the possibility of multiple myeloma.
Five, a sneeze and fracture alert multiple myeloma
Multiple myeloma is a plasma cell proliferative malignancy with a high incidence in the elderly. The most common complication of multiple myeloma is fracture, and patients often have bone pain as an early clinical symptom. Multiple myeloma can cause severe bone destruction. Moreover, most patients with multiple myeloma are elderly and have their own osteoporosis, which makes them more prone to fractures. Patients who work with heavy or heavier physical effort can easily cause severely damaged bones to break and fractures to occur. When sneezing, it may cause impact on the osteoporotic bones and lead to fracture. If you feel pain in your bones after sneezing and it persists without relief, you should be alert to bone problems and rule out the possibility of multiple myeloma.
VI. Multiple myeloma: reducing the rate of misdiagnosis is primary
Multiple myeloma occurs in middle-aged and elderly patients, accounting for 1% of all malignant tumors and 10% of hematologic tumors, and its incidence is increasing year by year as the population ages. Because of the diverse clinical manifestations of multiple myeloma, when clinical symptoms such as bone pain, back pain, anemia and weakness appear, patients often go to orthopedics, nephrology and neurology, but rarely first consult in hematology, thus misdiagnosis often occurs, and the initial misdiagnosis rate is as high as 70%. As multiple myeloma is a difficult disease to cure and extremely dangerous, early diagnosis and early treatment are important to prolong the survival of patients and are important measures to improve the effectiveness of multiple myeloma treatment.
Seven, the elderly back pain caution against multiple myeloma
Multiple myeloma cells infiltrate and secrete osteoclast-activating factor, leading to osteolytic damage, and more than 2/3 of patients have bone pain as the main first symptom, commonly in the chest and low back, which is aggravated by activities; the involved bones
More than 2/3 of patients have bone pain as the first symptom, commonly in the chest and low back, which worsens with activity. The symptoms of low back pain in the elderly should not be ignored as osteophytes or intervertebral disc disease, but should be examined in time to prevent multiple myeloma from being missed.
VIII. Where multiple myeloma is hidden
Patients with multiple myeloma cells when malignant plasma cells accumulate in large numbers in the bone marrow and become focally distributed. The malignant cells trigger the activation of osteoclasts, accompanied by the destruction of the bone cortex on the outside of the bone, triggering symptoms of bone pain, or they may infiltrate into tissues outside the bone marrow or near the bone, forming extramedullary plasmacytomas. After the treatment of multiple myeloma, a large number of malignant cells are killed and osteoblasts can repair the bone destruction site, but the repair process is slow, so the effect of bone treatment can be judged by taking X-rays once every 6 months.
Nine, the elderly bone pain alert multiple myeloma
Multiple myeloma cells will infiltrate and destroy bone tissue, forming osteolytic damage. After the bone is destroyed, sensory nerves in the periosteum will transmit signals to the brain, and people will feel pain. Bone pain is the most common first symptom of multiple myeloma, commonly in the chest and low back, and worsens with activity. Since multiple myeloma mostly occurs in the elderly, elderly people who feel pain in their bones should be alerted to the occurrence of multiple myeloma and seek timely medical examination.
X. Multiple myeloma disrupts the blood system
Multiple myeloma cells proliferate and infiltrate abnormally in the bone marrow, resulting in a reduction of normal hematopoietic space and inhibition of normal hematopoiesis; some factors secreted by myeloma cells also inhibit hematopoiesis, resulting in a decrease in the production of red blood cells, white blood cells and platelets, which can lead to anemia, bleeding and infection. In patients with multiple myeloma, renal function is reduced and erythropoietin secretion is decreased, which also affects the production of red blood cells. The abnormal monoclonal globulin (M protein) secreted by myeloma cells can wrap around the platelet surface and affect platelet function. Increased M-protein secretion and decreased secretion of normal immunoglobulins are also responsible for the occurrence of infections.