Treatment principles Asymptomatic stable myeloma does not require treatment and is followed up regularly; those with progressive elevation of M protein in blood or urine or clinical symptoms must be treated. Patients younger than 70 years of age should undergo hematopoietic stem cell transplantation if possible. For most myeloma patients with effective treatment, the main indexes such as M protein tend to stabilize within a certain period of time and enter the plateau phase, immunotherapy and dynamic observation can be given. General treatment 1. Health education: ① Bone marrow aspiration is one of the essential tests for the diagnosis of this disease, which is harmless and can be performed in elderly patients; ② The development of this disease is not as aggressive as acute leukemia, and most patients can be controlled with effective treatment; ③ The chemotherapy regimen used for the treatment of this disease is relatively mild, and the gastrointestinal reactions such as nausea and vomiting are mild, and most patients can tolerate them; ④ If the disease is not diagnosed and treated in a timely manner, it may develop into a serious disease. If the disease is not treated in time and develops into serious bone disease or even paraplegia or uremia, it will bring great pain and economic burden to patients and their families. Therefore, family members and patients should cooperate with the medical staff for active treatment. 2., general treatment: ① without spinal osteolytic lesions can be appropriate activities, with spinal lesions should limit the amount of activity to avoid the occurrence of compression fractures. ② Appropriate protein supplementation (those with renal insufficiency should have a low protein, high calorie diet), vitamins, electrolytes, etc. ③ Pay attention to mouth rinsing and perineal cleaning during chemotherapy and intervals to prevent oral infection, perineal infection and perianal abscess. Chemotherapy I. Traditional chemotherapy regimen: Marfannan and cyclophosphamide are more effective in chemotherapy of myeloma cells, but the efficacy of single drug is not as good as combined chemotherapy. Marfan is often excreted by the kidneys and is likely to damage hematopoietic stem cells. Therefore, regimens containing this drug should be avoided in patients with renal lesions or in preparation for hematopoietic stem cell transplantation. The following chemotherapy regimens are commonly used: 1. VAD regimen: V (vincristine): 0.4mg/d, sedation, day 1~4; A (adriamycin) 9mg/m2.d, sedation, day 1~4; D (dexamethasone) 40mg/d, sedation or oral, day 1~4, day 9~12, day 17~20. Every 4 weeks for a course of treatment. It is mostly used for the treatment of relapsed, refractory myeloma with an efficiency of about 30%. This regimen is widely used because it can also be applied to patients with renal lesions, does not damage hematopoietic stem cells, and has an effective rate of 60% for patients with primary myeloma. 2.M2 regimen: vincristine 1.2mg/m2, sedation, day 1; carazolamide 20mg/m2, sedation, day 1; cyclophosphamide 400mg/m2, sedation, day 1; marfalan 8mg/m2.d, oral, day 1~4; prednisone 20mg/m2.d, day 1~14. Repeat 1 course of treatment at 5-week interval. The efficiency of patients with primary myeloma is 60%. 3. MP regimen: Marfalan (M) 5mg/m2.d, orally, days 1~7; prednisone (P) 40mg/m2.d, days 1~7. Previously this regimen was used as the gold standard regimen for the treatment of myeloma, but due to its weak intensity, it was only used in elderly and frail patients. The effectiveness rate is 55-60%. Velcade inhibits endogenous nuclear factor KB (NF-KB induces MM apoptosis) and downregulates the adhesion molecules expressed by MM cells and stromal cells, thus reducing cytokine inhibition of drug resistance. It is widely used in clinical practice because it can overcome high-risk factors such as renal insufficiency and cytogenetic abnormalities, and can achieve complete remission (CR) of about 30% with an overall efficiency of 60-90%, significantly prolonging patient survival. The main side effects are dizziness, constipation, numbness in hands and feet and other clinical manifestations. Bortezomib 1.3 mg/m2 intravenous d1, 4, 8, 11, age greater than 75 years, or peripheral neuropathy and other side effects are not easily tolerated, can be reduced to 1.0 mg/m2 intravenous d1, 4, 8, 11, or 1.3 mg/m2 intravenous injection, once a week, 4 times a course of treatment. 2, reaction stop (also known as thalidomide, T): has a regulatory immune and anti-angiogenic effect, for the treatment of this disease single drug efficiency of about 30%. The dose is 100-200 mg/d. 3.Ralidomide (R): It is a new generation of immune modulating and anti-neovascular effect after thalidomide. It is an oral formulation and can be used for induction, consolidation and outpatient maintenance treatment of MM. The dose is 10-25mg/day. Radiotherapy It is mainly used for local radiotherapy of isolated and extramedullary plasmacytomas. Immunotherapy 1. Interferon: α-interferon can improve the complete remission rate of chemotherapy and prolong disease-free survival of patients. The dose is: 3 million U, subcutaneous injection, every other day. It is best to use it for more than six months. During the injection, patients may have flu-like symptoms such as fever, which can be relieved by oral antipyretics. Easy to apply on an outpatient basis. 2. Interleukin-2: mainly used to remove residual lesions. Hematopoietic stem cell transplantation Patients under 50 years of age should actively undergo hematopoietic stem cell transplantation; 50-70 years of age should be treated with discretion and in principle, hematopoietic stem cell transplantation should be performed as much as possible; over 70 years of age should not be performed. 1.Autologous hematopoietic stem cell transplantation: It is a great progress in the treatment of multiple myeloma, and its efficacy is significantly better than that of conventional chemotherapy. And the efficacy of secondary transplantation is better. Autologous peripheral blood stem cell transplantation can be performed, which is cheap, easy to operate and has been widely used for fast hematopoietic recovery. 2.Genetic hematopoietic stem cell transplantation: It is the only method to cure the disease, but the associated mortality rate is high and is mainly used for young patients with suitable donors. Support and symptomatic management 1.Anti-infection: antibiotics against G+ bacteria and G- bacteria need to be selected, and the possibility of fungal infection should be noted. 2. Correction of bone pain and hypercalcemia: give bisphosphonates 60-90 mg/dose intravenously for at least 6 hours once a month. Reduce the dosage appropriately in renal insufficiency. 3, the treatment of renal insufficiency: should be low protein, high calorie diet; avoid colds and other infections; avoid the application of drugs damaging to the kidney; correct constipation, high calcium, etc., as early as possible to perform dialysis treatment. 4. Correction of anemia: severe cases can be treated with erythropoietin, 8000-10000u IH 3 times/week. Course and prognosis The natural course of the disease is 6-12 months, and the median survival is up to 3-5 years after chemotherapy with traditional drugs. With the application of new targeted drugs, the survival of MM patients has been extended to 5-10 years, and in some cases even more than 10 years. The causes of death are infection, bleeding and renal insufficiency. Prognosis is related to many factors. Advanced disease, renal insufficiency, high levels of naive plasma cells, high levels of β2 microglobulin and IL-6, high expression of CD56 or CD138, and P53 gene expression are all factors of poor prognosis. Second, radiotherapy: High-dose (40Gy-50Gy) can be used as radical treatment for localized lesions, extramedullary plasmacytoma, and focal bone destruction. Low-dose radiotherapy (10Gy-20Gy) is used for palliative treatment of spinal nerve root compression, local bone pain, pathological fracture. A single 8Gy irradiation can be given for small subcutaneous tumors or painful osteolytic lesions in small cells. Long bones with significant osteolytic destruction may be given 20Gy/5 times before fracture. There is no improvement in survival with hemi-body irradiation. There are applications of total body irradiation with high-dose chemotherapy as pretreatment for allogeneic or autologous hematopoietic stem cell transplantation. However, recent findings suggest that conventional total body irradiation does not further increase tumor cell killing, but has greater toxic side effects, increases treatment-related complications and mortality, and delays the recovery of immune function. In recent years low-dose total body irradiation has been used for allogeneic transplantation. Radiotherapy alone or in combination with chemotherapy as a non-clearing pretreatment regimen has fewer complications and mortality and controls the disease through the anti-tumor effects of the graft. In patients who are expected to undergo total irradiation for HSCT, do not give multiple local radiation to avoid affecting the mobilization of HSCT. Symptomatic supportive treatment Complications that occur during the course of multiple myeloma, such as hypercalcemia, renal insufficiency, infection, bleeding, fracture, spinal cord compression, and anemia should be detected early and treated promptly to improve the quality of survival. Patients should be encouraged to be moderately active, drink more water and take soda to alkalize the urine. Chronic anemia (often accompanied by renal failure) can be treated with subcutaneous erythropoietin injections of 5,000-10,000 u every other day or 40,000 u once a week. Early antibiotics should be administered in case of infection, avoiding nephrotoxic antibiotics. Colony growth stimulating factor (G-CSF) may be given in cases of neutropenia. Bone pain and fractures should be treated with diclofosfamide and local radiotherapy. In hypercalcemia, hydration diuretics, diclofenac, mitomycin, and adrenocorticosteroids should be given. Hemodialysis can rapidly reduce blood calcium. In case of acute renal failure, dialysis should be performed.