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Multiple Myeloma

  Multiple myeloma (multiplemyeloma, MM) is the most common type of malignant plasma cell disease, also known as myeloma, plasma cell myeloma, or Kahler's disease. It was not until 1889, after Kahler's detailed report of cases, that multiple myeloma became widely understood and recognized by people. The characteristics of multiple myeloma are the malignant proliferation of monoclonal plasma cells and the secretion of a large amount of monoclonal immunoglobulins. The incidence rate is estimated to be 2-3/100,000, with a male-to-female ratio of 1.6:1, most patients are over 40 years old, and black patients are twice as many as white patients.

 

Table of Contents

1. What are the causes of multiple myeloma?
2. What complications can multiple myeloma easily lead to
3. What are the typical symptoms of multiple myeloma
4. How to prevent multiple myeloma
5. What laboratory tests should be performed for multiple myeloma
6. Diet taboos for patients with multiple myeloma
7. Conventional methods of Western medicine for the treatment of multiple myeloma

1. What are the causes of multiple myeloma?

  Multiple myeloma is a malignant tumor that results from the abnormal proliferation of plasma cells, leading to invasion of the bone marrow. It is a malignant plasma cell disease occurring in B lymphocytes. The etiology of multiple myeloma is not yet clear. In the dendritic cells of patients with multiple myeloma, a herpes virus related to Kaposi sarcoma was found, suggesting a certain association between the two. The virus encodes a homolog of interleukin-6 (IL-6). Human IL-6 can promote the growth of multiple myeloma and stimulate bone resorption. The specific cell of origin is not yet understood. Analysis of the immunoglobulin gene sequence and cell surface markers suggests that it originates from the post-germinal center cell malignant transformation.

2. What complications are prone to occur in multiple myeloma

  Multiple myeloma often causes the following complications;

  1. Fracture Pathological fracture, common in skull, pelvic, rib, vertebral bone fractures, etc.

  2. Hypercalcemia The incidence of hypercalcemia in myeloma patients in Europe and the United States can reach 30% to 60%, and clinical manifestations can include anorexia, nausea, vomiting, polyuria with thirst, and coma.

  3. Renal damage It is a common and important complication, and also one of the main causes of death in patients.

  4. Hypercoagulable syndrome The incidence rate in patients is 10%, usually manifested as vision decline, consciousness disorder, central nervous system disturbance, heart failure, etc.

  5. Hematological complications Anemia, hemorrhage, thrombosis.

  6. Infection Infection and fever may occur repeatedly during the course of the disease. Such as skin infection, pulmonary infection, etc.

  7. Amyloidosis It causes corresponding clinical manifestations, including tongue hypertrophy, parotid swelling, myocardial hypertrophy, cardiac enlargement, diarrhea, peripheral neuropathy, liver and spleen enlargement, etc.

  8. Neurological damage The incidence rate of neurological damage is 28.6% to 40%, including spinal cord compression, nerve root compression, etc.

3. What are the typical symptoms of multiple myeloma

  Multiple myeloma is a malignant tumor characterized by abnormal proliferation of plasma cells. Persistent, unexplained bone pain (especially in the back or chest), renal failure, recurrent bacterial infections (especially pneumococcal pneumonia) are the most common symptoms of multiple myeloma. Pathological fractures and vertebral compression are relatively common, the latter may lead to compression of the spinal cord and paraplegia. Due to widespread tubular cast formation, atrophy of renal tubular epithelial cells and interstitial fibrosis, renal failure (myeloma nephropathy) occurs. Some patients are mainly manifested by anemia, accompanied by fatigue and exhaustion, and a few patients have hypercoagulable syndrome. Lymph node and liver and spleen enlargement are not common.

4. How to prevent multiple myeloma

  The occurrence of multiple myeloma is related to environmental factors, diet, and other factors. Therefore, to prevent the occurrence of multiple myeloma, it is important to enhance physical fitness, actively treat chronic diseases, avoid contact with radiation and chemical toxins, and it is of great significance for the prevention and treatment of the disease.

  1. Avoid contact with carcinogens. If there is a history of contact or suspected symptoms, regular physical examinations should be arranged to achieve early detection and timely treatment.

  2. Participate in activities appropriately to reduce demineralization.

  3. Pay attention to personal hygiene, prevent infection, especially pay attention to the cleanliness of oral mucosa and skin, and prevent colds.

  4. Pay attention to emotional adjustment in traditional Chinese medicine, prevent excessive emotions, and thus maintain the smooth flow of Qi and blood, yin and yang balance, and prevent the occurrence of diseases.

5. What laboratory tests are needed for multiple myeloma

  1. Bone marrow examination: A certain proportion of abnormal plasma cells (myeloma cells are mainly primitive plasma cells or immature plasma cells) or tissue biopsy confirms the presence of myeloma cells.

  2. Large amounts of monoclonal immunoglobulins (monoclonal immunoglobulins can appear as a narrow peak at the γ, β, or α2 region of serum protein electrophoresis, also known as M protein) or urine monoclonal immunoglobulin light chains (i.e., urine Bence-Jones protein) are found in serum tests.

  3. (1) Immunotyping: The patient's bone marrow is examined, and the expression of B cell markers such as CD10, CD19, CD20 monoclonal antibodies, CD38, and CD138 plasma cell markers is increased.

  (2) Cytogenetic examination: It is mostly manifested as 14q+, del(14), t(11;14).

  (3) β2-microglobulin: It can be elevated in blood or urine and is a factor of poor prognosis. Especially, the blood level is not affected by renal function.

6. Dietary preferences and taboos for multiple myeloma patients

  1. Turtle Soup:500 to 1000g of turtle, appropriate amount of mushrooms. Preparation method: After killing and cleaning the turtle, add it to the mushrooms with seasonings and simmer over low heat until tender. It can be eaten with meals. It has the effects of nourishing Yin and blood. It is suitable for patients with multiple myeloma who have been injured in both Qi and blood during chemotherapy.

  2. Longan Meat Porridge:15g of longan meat, 3 to 5 jujube fruits, 100g of glutinous rice. Preparation method: Cook all the above ingredients into porridge, and take it hot. Take one bowl in the morning and evening each time. The amount should not be too much each time. It has the effects of nourishing Qi and blood. It is suitable for multiple myeloma nephropathy with deficiency of both Qi and blood.

  3. Peach Blossom Fish Fillets:100g of crucian carp, 10g of peach kernel powder. Preparation method: After killing and cleaning the crucian carp, cook it with peach kernel powder and other seasonings such as oil and salt. It can be eaten with meals. It has the effects of promoting blood circulation and nourishing the kidney. It can inhibit excessive bone marrow proliferation and is suitable for multiple myeloma.

  4. Catfish and Black Bean Soup:Silver carp (barbless catfish) 1 to 2 pieces (about 500g), black beans 50 to 100g, jujube 6 to 10 pieces. Preparation method: After killing and cleaning the fish, add it to the water with black beans and jujube, and cook with oil and refined salt for seasoning. It can be eaten with meals. It can be consumed alternately with the Yellow Catfish and Yam Soup and taken regularly. It has the effects of nourishing blood, nourishing the kidney, regulating the middle, and invigorating the yang. It is suitable for multiple myeloma caused by insufficient spleen and kidney.

  5. Yellow Catfish and Yam Soup:Yellow catfish 1 to 2 pieces, yam 50 to 100g, ginger 2 slices. Preparation method: Kill and clean the yellow catfish, slice the yam, and cook with water, oil, salt, and other seasonings over low heat. It can be eaten with meals or used to cook rice with yellow catfish. Long-term consumption has the effects of sweet, warm, and replenishing the middle and benefiting blood. It is suitable for multiple myeloma caused by insufficient middle-jiao.

7. Conventional methods of Western medicine for the treatment of multiple myeloma

  1. Treatment

  1. Supportive therapy

  (1) Long-term bedridden patients are prone to bone demineralization, hypercalcemia, renal insufficiency. Encouraging patients to engage in appropriate and regular activities can help improve the above conditions. If bone pain limits activity, analgesics or local radiation can be used to achieve pain relief. Patients with lesions in the ribs, sternum, or thoracolumbar spine should use light, corrective supports for protection, which can alleviate pain and prevent pathological fractures. For patients with severe compression fractures of the thoracic and (or) lumbar spine and the possibility of spinal cord injury leading to paraplegia, activity should be restricted. Patients with osteolytic lesions in the thoracic and lumbar spine should sleep on a hard bed with soft padding to prevent excessive spinal curvature and fractures that may damage the spinal cord.

  (2) Anemia should be improved or corrected, transfusing red blood cells to maintain hemoglobin concentration above 80g/L to improve the general condition of the patient, enabling them to tolerate chemotherapy. Subcutaneous or intravenous injection of erythropoietin (erythropoietin, EPO) helps to improve anemia. When thrombocytopenia causes bleeding, concentrated platelet suspension can be transfused. When the hypercoagulable syndrome is severe, plasma exchange can be used to quickly remove the abnormal large amount of immunoglobulin, reduce plasma viscosity, and alleviate symptoms. Hypercalcemia is treated with intravenous injection of calcitonin (calcitonin) 5-10U/(kg·d), intravenous infusion of pamidronate disodium (Bonin, Actada) 60-90mg/d, and oral prednisone (60mg/d) can effectively reduce blood calcium. For patients with hyperuricemia, oral allopurinol (allopurinol) 300-600mg/d can effectively reduce blood uric acid levels. Dehydration is caused by factors such as increased urine calcium leading to polyuria, renal tubular dysfunction leading to polyuria, and hypercalcemia leading to vomiting. In treatment, on the one hand, fluid replacement is given to achieve urine output of 1500-2000ml/d, and on the other hand, hypercalcemia is treated in a timely manner. For patients with renal insufficiency, treatment is handled according to the principles of renal insufficiency treatment.

  ① If hemoglobin is below 60g/L, transfuse red blood cells; ② Hypercalcemia: isotonic saline hydration, prednisone: 20mg, oral, 3-4 times a day; ③ Hyperuricemia: allopurinol: 0.2mg, oral, 3 times a day; ④ Hypercoagulability: plasma exchange therapy; ⑤ Renal failure: hemodialysis; ⑥ Infection: combined use of antibiotics for treatment, and penicillin and gamma globulin prophylactic injection are effective for patients with recurrent infections.

  Patients with this disease are prone to concurrent infections, and attention should be paid to preventing colds, maintaining oral hygiene, and using effective antibiotics against the pathogen once infection occurs, in order to control the infection early. Intramuscular injection of human blood gamma globulin is difficult to achieve effective prevention of infection, and the role of intravenous infusion of high-dose human blood gamma globulin in the prevention and treatment of infection in this disease is still under study.

  2. Chemotherapy

  Chemotherapy is the main treatment method for this disease, and the application of new chemotherapy drugs and the improvement of medication methods are key factors for the improvement of efficacy in recent years.

  As monotherapy, alkylating agents such as Lomustine (milrafan, levophenylalanine mustard), cyclophosphamide, nitrogen mustard (formylsarcosine, N-methyl), procarbazine (methylbenzhydrazine), carmustine (bis-chloroethyl nitrosourea, BCNU), lomustine (chloroethylcyclohexyl nitrosourea, CCNU), vincristine, doxorubicin (adriamycin), etoposide (teniposide, VP16) and others have efficacy.

  (1) Regimen: The most long-used and effective regimen is the combination chemotherapy regimen.

  ①MP regimen: Lomustine (Melfal) 8mg/m2, taken orally from the 1st to the 4th day (or 4mg/m2, taken orally from the 1st to the 7th day); Prednisone 60 to 80mg, taken orally from the 1st to the 7th day; 4 weeks as a course of treatment, the efficacy rate of MP is about 50%, with a median survival period of 24 to 30 months, 80% of patients die within 5 years.

  ②M2 regimen: Carmustine (BCNU) 0.5mg/kg, administered intravenously on the 1st day; Cyclophosphamide 10mg/kg, administered intravenously on the 1st day; Lomustine (Melfal) 0.25mg/kg, taken orally from the 1st to the 4th day; Prednisone 1mg/kg, taken orally from the 1st to the 7th day, 0.5mg/kg, taken orally from the 8th to the 14th day; Vincristine 0.03mg/kg, administered intravenously on the 21st day; 5 weeks as a course of treatment.

  ③VBMCP regimen: Vincristine 1.2mg/m2, administered intravenously on the 1st day; Carmustine (BCNU) 20mg/m2, administered intravenously on the 1st day; Lomustine (Melfal) 8mg/m2, taken orally from the 1st to the 4th day; Cyclophosphamide 400mg/m2, administered intravenously on the 1st day; Prednisone 40mg/m2, taken orally from the 1st to the 7th day, 20mg/m2, taken orally from the 8th to the 14th day; 5 weeks as a course of treatment.

  ④VMCP/VBAP regimen: Vincristine 1mg/m2, administered intravenously on the 1st day; Lomustine (Melfal) 6mg/m2, taken orally from the 1st to the 4th day; Cyclophosphamide 125mg/m2, taken orally from the 1st to the 4th day; Prednisone 60mg/m2, taken orally from the 1st to the 4th day; 3 weeks as a course of treatment; Vincristine 1mg/m2, administered intravenously on the 1st day; Carmustine (BCNU) 30mg/m2, administered intravenously on the 1st day; Doxorubicin (Adriamycin) 30mg/m2, administered intravenously on the 1st day; Prednisone 60mg/m2, taken orally from the 1st to the 4th day; 3 weeks as a course of treatment, alternating use of the two regimens.

  (2) Currently, the VAD regimen or high-dose Lomustine (Melfal) (HDM) regimen is commonly used to treat refractory cases.

  ①VAD regimen: Vincristine 0.4mg/24h continuously infused intravenously for 4 days, Doxorubicin (Adriamycin) 10mg/(m2·24h) continuously infused intravenously for 4 days, Dexamethasone 40mg, taken orally, from the 1st to the 4th day, from the 9th to the 12th day, from the 17th to the 20th day, and on the 25th day as a course of treatment. This regimen has an efficacy rate of 45% to 66% for refractory cases, with a median survival period of 11 to 16 months. The main side effect is secondary infection caused by high-dose dexamethasone. For refractory cases confirmed to have high expression of multidrug resistance genes, MDR reverse agents, such as Verapamil (Inderal) 40 to 80mg taken orally, 3 times a day, or Cyclosporine 4mg/kg, administered intravenously, 2 times a day, from the 1st to the 3rd day, 2.5mg/kg administered intravenously, 2 times a day, from the 4th to the 5th day, or 1:3 taken orally, Cyclosporine (CsA) 5mg/(kg·d).

  ② High-dose phenylalanine mustard (melphalan) regimen: phenylalanine mustard (melphalan) 50-100 mg/m2, intravenous injection, on the first day. The efficacy rate of this regimen is about 40%, and the main side effect is bone marrow suppression, which needs to be paid attention to.

  (3) In addition to the aforementioned VAD, VAD plus MDR reverser, and HDM regimen, for refractory cases, the CBV (cyclophosphamide, carmustine (BCNU), etoposide) regimen or EDAP (etoposide, dexamethasone, doxorubicin, cisplatin) regimen can also be chosen. Both regimens have an efficacy rate of about 40%. There are reports that the macrolide antibiotic clarithromycin (clarithromycin) 500 mg, twice a day, is effective for the disease, and may also be effective for cases resistant to chemotherapy. Oral thalidomide (sedative) is gradually increased from 200 mg/day to 400-800 mg/day, and the medication duration is more than 6 weeks, with an efficacy rate of about 30%. Side effects include drowsiness, constipation, fatigue, peripheral neuropathy, etc.

  3. Interferon and other biological response modifiers

  Interferon is a cytokine with multiple functions, including antiviral activity, influencing (inhibiting or stimulating) cell growth, and regulating immunity. The effect of interferon on cell growth (including tumor cells) is often manifested as inhibition. At the same time, interferon also activates natural killer cells, activates cytotoxic T cells, and stimulates B cells to synthesize immunoglobulins, among other regulatory immune functions. Therefore, it is used in the treatment of tumors, including this disease. Interferon alpha is administered subcutaneously at a dose of (3-5) × 10^6 U, three times a week, for at least 6 weeks. The efficacy rate of monotherapy in initially treated patients is 10%-20%, mostly partial remission. If combined with chemotherapy, whether it is superior to chemotherapy alone is still controversial. Although many reports confirm that the combination of chemotherapy and interferon alpha can improve the response rate and prolong the duration of remission, some reports suggest that the addition of interferon alpha has no effect on efficacy. As for refractory cases, all reports agree that interferon alpha is difficult to be effective. For maintenance treatment after complete remission from chemotherapy, although some studies hold a negative attitude, most studies confirm that the application of interferon alpha [(3-5) × 10^6 U subcutaneously, three times a week, long-term injection] as maintenance therapy can achieve the effect of prolonging the duration of remission. This controversy awaits further research clarification.

  (1) Interleukin-6 (IL-6) is an important cytokine that induces B cell differentiation and stimulates the growth of B cell-plasmacyte, which is required for the in vitro culture of human myeloma cells. The levels of IL-6 in the bone marrow and serum of myeloma patients are significantly elevated, indicating that IL-6 plays an important role in the pathogenesis of the disease. Therefore, studies have applied anti-IL-6 monoclonal antibody therapy for the disease, with preliminary reports showing some efficacy, but further research is needed to confirm this.

  (2) Bone pain is one of the main symptoms of this disease. Pamidronate disodium (Bonine, Actada) reduces bone pain and osteolytic lesions by inhibiting osteoclast activity. The dosage is 60-90mg, intravenous infusion, once a month, and can be repeated. Recently, the application of OAF inhibitors (SD-7784, Statins) in the treatment of osteolytic lesions has entered clinical trials.

  4. Radiation therapy

  Radiation therapy is applicable to the treatment of solitary osteoplastic plasmacytoma and extramedullary plasmacytoma that is not suitable for surgical resection, and it is also an effective treatment method to alleviate severe local bone pain. In addition, for patients with recurrent or resistant diseases who are ineffective to chemotherapy, partial body irradiation or partial body irradiation combined with combined chemotherapy is used, with an efficacy rate of about 50%. The radiation dose is generally 625cGy for the upper body or 850cGy for the lower body. In recent years, due to the progress of bone marrow transplantation, total body irradiation is often used as one of the pretreatment measures before transplantation and is no longer used alone.

  5. Surgical treatment

  When osteolytic lesions occur in the thoracic or lumbar spine, causing the patient to be bedridden and possibly leading to paraplegia due to compression fractures, vertebral resection and artificial vertebral body replacement and fixation can be performed. Successful surgery will enable the patient to avoid paraplegia, restore activity to some extent, and improve the quality of life.

  6. Hematopoietic stem cell transplantation

  Although chemotherapy has achieved significant efficacy in this disease, it has not cured the disease. Therefore, since the 1980s, bone marrow transplantation combined with high-dose chemotherapy and total body irradiation has been tried to cure the disease, and allogeneic, syngeneic, and autologous bone marrow (including peripheral blood stem cells) transplantation have all been applied in the clinical treatment of this disease.

  The purpose of pretreatment before bone marrow transplantation is to clear tumor cells in the patient's body and suppress the patient's immune function to make the bone marrow easy to engraft. For this disease, high-dose phenylalanine mustard (Melfalan) 140-200mg/m2 (-2 days) and total body irradiation (TBI) 850cGy (-1 day) are commonly used as pretreatment, and carmustine (BCNU) 120mg/m2 (-8 days), etoposide (Teniposide) 250mg/m2 (-8 days, -6 days), phenylalanine mustard (Melfalan) 140mg/m2 (-2 days) and TBI 850cGy (-1 day) are also used as pretreatment. Recent summary studies believe that using phenylalanine mustard (Melfalan) 200mg/m2 alone as pretreatment has a relatively good effect.

  ① Allogeneic bone marrow transplantation: A report from the Center for Research in Seattle, USA, states that 7 patients with this disease received allogeneic bone marrow transplantation from their identical twin brothers, among whom 2 cases have survived without disease for 8 and more than 15 years respectively (1994). Sweden reported 6 cases of allogeneic bone marrow transplantation, among which 3 cases have survived for more than 6 years, indicating that bone marrow transplantation may cure this disease;

  ② Allogeneic bone marrow transplantation: The European Bone Marrow Transplantation Organization reported 90 cases, the Seattle group in the United States reported 50 cases, Italy reported 27 cases, and Canada reported 17 cases of patients with this disease who underwent allogeneic bone marrow transplantation. The results were similar: the 4-year survival rate was about 30%, and the 10-year survival rate was about 20%, but the transplantation-related mortality rate was as high as 40% to 50%. The infusion of donor T lymphocytes depleted of CD8 in patients with relapse after allogeneic bone marrow transplantation may produce graft-versus-tumor effect (GVL) and allow some patients to regain remission. It is currently generally believed that allogeneic bone marrow transplantation has a certain efficacy and may cure some patients, but this therapy has certain risks, especially the incidence of graft-versus-host disease (GVHD) and the mortality rate associated with bone marrow transplantation are relatively high. Therefore, attention should be paid to selecting appropriate cases for allogeneic bone marrow transplantation. Most scholars advocate that patients with poor prognosis who are younger than 55 years old and have HLA-matched related marrow donors should strive to undergo bone marrow transplantation as soon as possible. For patients with the above conditions but good prognosis, bone marrow transplantation should be delayed until the first recurrence.

  ③ Autologous bone marrow transplantation: Due to the difficulty in ensuring the complete clearance of tumor cells in patients' bodies with the current pre-treatment regimen, and the lack of effective in vitro purification methods for bone marrow, the recurrence rate after autologous bone marrow transplantation is relatively high, and the efficacy is limited. Although there are reports confirming that autologous bone marrow transplantation can improve the remission rate, there is no definitive conclusion on whether it can extend the remission period. The improvement of efficacy in this disease depends on the improvement of the pre-treatment regimen and the progress of in vitro bone marrow purification research;

  ④ Autologous peripheral blood stem cell transplantation: The advantage of using this method to treat the disease is that only a small number of tumor cells are present in the peripheral blood of patients with this disease. It is usually performed in the early stage of bone marrow hematopoietic function recovery after chemotherapy, in combination with the application of G-CSF and other cytokines to mobilize bone marrow hematopoietic stem cells into peripheral blood for collection and storage. After the patient receives high-dose chemotherapy and TBI, it is then reinfused into the patient. The efficacy reported by different medical centers varies, and it is generally believed that autologous peripheral blood stem cell transplantation may be superior to simple chemotherapy in terms of both remission rate and disease-free survival period, but it is inevitable that relapse will occur. Research on this therapy is currently being actively carried out.

  7. CD20 monoclonal antibody therapy

  Rituximab (MabThera) 375mg/m2 for multiple myeloma, once a week for 4 weeks, a total of 4 times for one cycle, an interval of 6 months for the second cycle, a total of 6 cycles. On the 35th day of administration of rituximab (MabThera), 0.25mg/kg of phenylalanine mustard (Mustargen) is given orally from the 1st to the 4th day, 100mg of prednisone is given orally from the 1st to the 4th day, and repeated every 4 to 6 weeks.

  The criteria for efficacy judgment: The important indicators for judging the efficacy of this disease are: the serum M protein and/or urine Bence-Jones protein decreased by more than 50%, the plasma cell tumor with the two largest diameters reduced by more than 50%, and the improvement of osteolytic bone damage, secondary criteria, the reduction of plasma (tumor) cells in the bone marrow

  II. Prognosis

  Factors related to the prognosis of the disease include: clinical stage (including renal function), immunoglobulin typing, differentiation degree of plasma (tumor) cells, serum β2-microglobulin level, serum lactate dehydrogenase level, and plasma cell marker index. The median survival of clinical stage IA can reach 5 years, while the median survival of clinical stage IIIB is less than 2 years. The type of immunoglobulin also affects the prognosis, with the light chain type having a poorer prognosis, and the IgA type also being inferior to the IgG type. Poorly differentiated plasma (tumor) cells have a poorer prognosis than well-differentiated plasma (tumor) cells. β2-microglobulin (β2-microglobulin, β2-M) is a low molecular weight (11800) protein and is the light chain part of the HLA-A, B, C tissue compatibility antigen complex. The normal serum β2-M content

  The course of the disease varies greatly among different patients. According to the analysis of the above prognostic factors, patients with the disease can be divided into low-risk group, medium-risk group, and high-risk group. There is currently no universally recognized, unified classification standard. The following classification criteria are for reference only. The low-risk group is at stage I at diagnosis, such as β2-M5 years; the medium-risk group is at stage II at diagnosis, β2-M≥2.7mg/L or PCLI≥1%, the median survival of this group is about 3 years; the high-risk group is at stage III at diagnosis, β2-M≥2.7mg/L, and PCLI≥1%, the median survival of this group is about 1.5 years. In terms of the overall condition of the disease, under the current conditions of chemotherapy as the main treatment, the median survival of patients with the disease is 30 to 36 months. The main causes of death in patients are infection, renal failure, systemic failure or multi-organ failure due to progression of myeloma, and a few patients die due to gastrointestinal or intracranial hemorrhage. About 5% of patients transform into acute leukemia, most of which are acute plasma cell leukemia, but can also be acute monocyte leukemia, acute granulocyte-monocyte leukocyte, or acute granulocytic leukemia.

 

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