What Is the Prognosis for Multiple Myeloma?

Multiple myeloma (MM) is a malignant plasma cell disease. Its tumor cells originate from plasma cells in the bone marrow, and plasma cells are cells that develop B lymphocytes to the final functional stage. Therefore, multiple myeloma can be classified as B lymphocytic lymphoma. Currently, it is classified by WHO as a type of B-cell lymphoma, called plasma cell myeloma / plasmacytoma. It is characterized by abnormal proliferation of bone marrow plasma cells accompanied by excessive production of monoclonal immunoglobulin or light chain (M protein). Very few patients can be unsecreted MM that does not produce M protein. Multiple myeloma is often accompanied by multiple osteolytic lesions, hypercalcemia, anemia, and kidney damage. Since the production of normal immunoglobulins is suppressed, various bacterial infections are prone to occur. The incidence is estimated to be 2 to 3 / 100,000, with a male to female ratio of 1.6: 1, and most patients are over 40 years old.

Basic Information

English name

multiple myeloma (MM)

Visiting department

Hematology

Multiple groups

Over 40, especially those over 60

Common causes

unknown

Common symptoms

Anemia, bone pain, renal insufficiency, infection, bleeding, neurological symptoms

Contagious

no

Multiple myeloma staging

Staging	Durie and Salmon staging criteria (1975)	ISS international prognostic staging criteria (2005)	Revised R-ISS international prognostic staging criteria (2015)
I	Meet the following 4 items: Hemoglobin> 100g / L Serum calcium is normal No bone destruction M protein level IgG <50g / L IgA <30g / L Urine light chain <4g / 24h	Serum 2 microglobulin <3.5mg / L Albumin 35g / L	Meet the criteria of ISS staging I; And lactate dehydrogenase are normal; And iFISH inspection is normal (need to comply with 3)
	Neither Phase I nor Phase III	Between Phases 1 and 3	Between R-ISS stages and
	Meet one or more of the following: Hemoglobin <85g / L Hypercalcemia Progressive osteolytic disease M protein level: IgG> 70g / L IgA> 50g / L Urine light chain> 12g / 24h	Serum 2 microglobulin 5.5mg / L	Meet the criteria of ISS Stage III; Or combined with increased lactate dehydrogenase; Or combined iFISH examination abnormality showed high risk, that is, chromosome 17p13 deletion, and / or t (4; 14) and / or t (14; 16) (subject to 2)
Subgroup standard	Normal renal function in group A (blood creatinine <2.0mg / dL) Kidney function abnormal in group B (blood creatinine 2.0mg / dL)		R-ISS: revised international prognostic staging; FISH: fluorescence in situ hybridization; iFISH: refers to the intermediate-term FISH after screening with CD138 (a marker for positive expression of myeloma cells) magnetic beads. The FISH after screening is detected compared to ordinary FISH The positive rate is high.

Clinical manifestations of multiple myeloma

Multiple myeloma begins slowly and has no obvious symptoms in the early stage, which is easy to be misdiagnosed. The clinical manifestations of MM are diverse, mainly including anemia, bone pain, renal insufficiency, infection, bleeding, neurological symptoms, hypercalcemia, amyloidosis, etc.

1. Bone pain, bone deformation and pathological fracture

Myeloma cells secrete osteoclast active factors and activate osteoclasts to dissolve and destroy bone. Bone pain is the most common symptom, mostly lumbosacral, sternum, and rib pain. Due to the destruction of bone by tumor cells, pathological fractures can occur, and multiple fractures can exist at the same time.

2. Anemia and bleeding

Anemia is more common and is the first symptom. It is mild in the early stage and severe in the later stage. Thrombocytopenia may occur at an advanced stage, causing bleeding symptoms. Skin and mucosal hemorrhage are more common, and in severe cases, visceral and intracranial hemorrhage can be seen.

3. Liver, spleen, lymph node and kidney disease

Swelling of liver and spleen, lymphadenopathy of neck, myeloma and kidney. Enlarged or abnormal masses require extramedullary plasmacytomas or amyloidosis.

4. Nervous system symptoms

Extramedullary plasmacytoma of the nervous system can appear limb paralysis, drowsiness, coma, diplopia, blindness, and vision loss.

5. Multiple bacterial infections are common in multiple myeloma

Fungal and viral infections can also be seen. The most common are bacterial pneumonia, urinary tract infections, and sepsis. Viral zoster is also prone to occur, especially in patients with low immunity after treatment.

6. Impaired renal function

50% to 70% of patients have protein, red blood cells, white blood cells, casts, urine, chronic renal failure, hyperphosphatemia, hypercalcemia, hyperuricemia, and can form uric acid stones.

7. High viscosity syndrome

Dizziness, vertigo, and visual impairment can occur, and sudden syncope and disturbance of consciousness can occur.

8. Amyloidosis

Often occurs in the tongue, skin, heart, gastrointestinal tract and other parts.

9. Mass or Plasma Cell Tumor

Some patients can have a mass with a diameter ranging from a few centimeters to a few tens of centimeters. It can be a bony mass or a soft tissue mass. These pathological examinations are mostly plasmacytomas. It is generally believed that patients with soft tissue masses or plasmacytomas have a poor prognosis and short survival.

10. Thrombosis or infarction

Patients may have hemodialysis fistula infarction, deep vein thrombosis, or myocardial infarction. The cause is related to factors such as susceptibility to tumor thrombosis and hyperviscosity syndrome.

Multiple myeloma test

Biochemical routine inspection

Serum abnormal globulin is increased, while albumin is normal or decreased. Urocoagulin (also known as Urinary week protein) is half positive.

The patient's protein electrophoresis or M protein identification results will appear characteristically sharp "M peak" or "M protein". Therefore, in the routine biochemical examination, if the total amount of globulin increases or an abnormally high "M peak" appears in protein electrophoresis, you should go to the hematology department, except for the diagnosis of myeloma.

Blood test

Anemia is mostly positive cells, positive pigmentation, normal or low platelets.

3. Bone marrow examination

The abnormal increase in the number of plasma cells is 10%, which is a primitive or naive plasma cell with abnormal morphology.

4. X-ray examination of bones

Visible multiple osteolytic puncture-like osteoporosis or osteoporosis, pathological fractures.

For bone damage in patients with MM, CT, nuclear magnetic resonance (MRI), etc. are generally considered to have a better chance of finding lesions than X-ray examinations; the sensitivity of these imaging methods to bone lesions is: PET-CT> MRI> CT> X-ray.

5. Biological examinations such as chromosomes and fluorescence in situ hybridization (FISH)

Bone marrow chromosome 17p13 deletion and / or t (4; 14) and / or t (14; 16) abnormalities often indicate high risk. Fluorescence in situ hybridization (FISH), especially the use of CD138 (positive expression in most myeloma cells) magnetic beads purified FISH, iFISH test, can improve the positive rate of the test. This test has been used in the newly revised international prognostic staging system (R-ISS staging system) in 2015.

6. Serum free light chain inspection

It is more sensitive than ordinary blood or urine light chain tests, and has been defined by the International Myeloma Working Group (IMWG) experts as the strict standard for complete response (sCR). After treatment of MM patients, the serum free light chain changes from positive to negative, and the effect is strict and complete remission.

Multiple Myeloma Diagnosis

(I) MM criteria for diagnosis by the World Health Organization (WHO) (2001)

Main criteria

(1) Increase in bone marrow plasma cells (> 30%)

(2) Plasma cell tumor confirmed by tissue biopsy

(3) M-component: serum IgG> 3.5g / dL or IgA> 2.0g / dL, urine weekly protein> 1g / 24h.

2. Minor criteria

(1) Increase in bone marrow plasma cells (10% to 30%)

(2) M-component is present but its level is lower than the above level

(3) with osteolytic lesions

(4) The normal immunoglobulin is reduced by more than 50%: IgG <600mg / dL, IgA <100mg / dL, IgM <50mg / dL.

3. Diagnostic MM requirements

Have at least 1 primary standard and 1 secondary standard; Or have at least 3 secondary standards and must include (1) and (2) of them. Patients should have progressive symptoms associated with the diagnostic criteria.

(II) MM diagnostic criteria by the International Myeloma Working Group (IMWG) (2003)

Symptomatic MM

(1) M-protein in blood or urine

(2) clonal plasma cells or plasma cell tumors in the bone marrow

(3) Relevant organ or tissue damage (end organ damage including hypercalcemia, kidney damage, anemia or bone damage)

2. Asymptomatic MM

(1) M-protein 30g / L

(2) and / or clonal plasma cells in bone marrow 10%

(3) No related organ or tissue damage or asymptomatic

IMWG experts believe that asymptomatic MM patients, even if diagnosed with MM, can closely observe patients before they develop terminal organ damage such as hypercalcemia, kidney damage, anemia, or bone damage; once hypercalcemia, Kidney damage, anemia, or bone damage is one of the end organ damages that has to start treatment.

Differential diagnosis of multiple myeloma

Certain chronic diseases (such as rheumatic system disease, chronic tuberculosis infection, kidney disease, chronic liver disease, etc.) or lymphoma can cause reactive plasmacytosis and unclear monoclonal monoclonal globulinemia (MGUS), which needs to be performed with MM Differential diagnosis; In addition, some severe osteoporosis or hypophosphatemic bone disease or metastatic cancer need to be distinguished from MM's bone destruction.

Multiple myeloma treatment

Treatment principle

(1) In general, asymptomatic MM patients do not require treatment; symptomatic myeloma does not start treatment.

(2) 80% of high-risk asymptomatic patients can be converted to MM within 2 years, which can be treated early.

High-risk asymptomatic MM is defined as: abnormal plasma cells in the bone marrow 60%; creatinine clearance <40 ml / min; serum free light chain ratio 100; evidence of the following active lesions on bone imaging: Resonance (MRI) 1 bone lesion; PET-CT was positive; low-dose CT of the whole body revealed bone lesions> 5m.

2. General treatment

(1) Transfusion of red blood cells with hemoglobin below 60g / L or subcutaneous injection of erythropoietin if necessary.

(2) Hypercalcemia isotonic saline hydration, prednisone, calcitonin, bisphosphonate drugs, primary disease treatment.

(3) Hydration of hyperuricemia , allopurinol is taken orally.

(4) Hyperviscosity treatment of primary disease, temporary plasma exchange if necessary.

(5) Renal failure treatment of primary disease, hemodialysis if necessary.

(6) Infection Combined with antibiotics, it is effective for patients with recurrent infections and regular preventive gamma globulin injections.

3. chemotherapy

Commonly used drugs include: targeted drugs are currently mainly proteasome inhibitors (bortezomib, carfilzomib) and immunomodulators (thalidomide, lenalidomide, or pomalidomide); Chemotherapy drugs include melphalan, doxorubicin and cyclophosphamide; glucocorticoids such as dexamethasone and prednisone.

Commonly used chemotherapy regimens are: proteasome inhibitors / immunomodulators + glucocorticoids; or proteasome inhibitors / immunomodulators + conventional chemotherapy drugs + glucocorticoids; or traditional chemotherapy drugs + glucocorticoids (belonging to traditional chemotherapy Program).

It has been proven that the efficacy of the new drugs containing proteasome inhibitors / immunomodulators is significantly better than traditional chemotherapy. Therefore, patients with MM should be treated with a new drug containing proteasome inhibitors / immunomodulators as much as possible.

(1) Patients who are suitable for autologous transplantation adopt a joint scheme without Melphalan to avoid damage to hematopoietic stem cells;

(2) Patients who are not suitable for autologous transplantation. For elderly patients older than 65 years, the traditional medicine can be combined with a malafrain-containing scheme.

4. Hematopoietic stem cell transplantation

All eligible patients are recommended for autologous hematopoietic stem cell transplantation, and some young and high-risk patients may consider allogeneic hematopoietic stem cell transplantation as appropriate.

5. Radiotherapy

For localized myeloma, local bone pain, and those with spinal cord compression symptoms.

Multiple myeloma prognosis

Factors affecting the prognosis of MM are:

1. Some chromosomal abnormalities: for example, chromosome 13 is deleted, 17p13 is deleted, and 14q32 is ectopic.

2. Plasma cell marker index.

3. 2-microglobulin levels.

4. Serum albumin levels.

5. Serum creatinine levels.

6. Older age: over 75 years old.

7. Plasma lactate dehydrogenase levels.

8. Multiple extramedullary plasmacytomas.

9. Plasma soluble IL-6 receptor levels.

10. C-reactive protein levels.