What Is Waldenstrom's Macroglobulinemia?

There is abnormally increased lgM in the blood, which is macroglobulinemia. This disease is divided into primary and secondary, and the increase in unexplained monoclonal lgM is called primary macroglobulinemia (Waldenstrom macroglobulinemia). Monoclonal or polyclonal lgM secondary to other diseases The increase is called secondary macroglobulinemia. The clinical manifestations of primary macroglobulinemia are characterized by aging, anemia, bleeding tendency, and hyperviscosity syndrome. The diagnosis was based on the presence of a large amount of monoclonal lgM in the blood and lymphoid plasma cell infiltration in the bone marrow. The disease is a chronic process. Chemotherapy is not recommended when there are no clinical symptoms. Chemotherapy is used for progressive diseases.

Hu Ying

(Deputy Chief Physician)

Department of Hematology and Oncology, West District, Beijing Chaoyang Hospital, Capital Medical University

Macroglobulinemia is an abnormal increase in lgM in the blood. There are primary and secondary macroglobulinemia. Primary macroglobulinemia has a genetic predisposition. It is not certain whether it is related to environmental factors. Chronic antigenic stimulation caused by infection, autoimmune disease, or special occupational exposure is not clearly related to primary macroglobulinemia, and whether it is related to viral infection remains to be determined. Common symptoms include fatigue, weakness, weight loss, paroxysmal bleeding, and hyperviscosity syndrome.

Western Medicine Name: Macroglobulinemia
Affiliated Department: Internal Medicine-Hematology
Disease site: blood
The main symptoms: Fatigue, weakness, weight loss, paroxysmal bleeding and hyperviscosity syndrome

Main cause: Heredity
Multiple groups: male
Contagious: Non-contagious

Macroglobulinemia disease profile

Macroglobulinemia disease classification

The diseases that cause macroglobulinemia can be divided into three categories:

Benign monoclonal macroglobulinemia and cold agglutinin syndrome.

Plasma cell disease is primary macroglobulinemia, lgM type multiple myeloma and extramedullary plasma cell tumor.

B lymphocytic tumors are chronic lymphocytic leukemia and lymphoma.

Macroglobulinemia definition

Macroglobulinemia is a malignant proliferative disease derived from B lymphocytes that can differentiate into mature plasma cells. It has its unique clinical and pathological characteristics. It is mainly manifested by the infiltration of plasma cell-like lymphocytes in the bone marrow and the Clone lgM. It is a disease with the lymphomas defined by the revised European and American lymphoma and the World Health Organization classification system.

Causes of macroglobulinemia

Macroglobulinemia accounts for about 2% of all hematological tumors and is a rare disease. The Caucasian population has a higher incidence, and African descent accounts for only 5% of all patients with macroglobulinemia. There are a large number of reports of familial diseases, including macroglobulinemia and other B-lymphocyte proliferative diseases. This shows that genetic factors are important. The study observed 181 macroglobulinemia patients, about 20% of their first-degree family members suffered from macroglobulinemia or other B-cell diseases, and healthy relatives were also susceptible to other immunological diseases, with hypogammaglobulinemia Disease, hypergammaglobulinemia (especially polyclonal lgM), production of autoantibodies (especially for thyroid), and increased number of active B cells. Whether it is related to environmental factors is uncertain. Chronic antigenic stimulation caused by infection, autoimmune disease, or special occupational exposure is not clearly associated with macroglobulinemia. Whether it is related to a viral infection remains to be determined. There is also controversy about the correlation between HCV, HHV-8 and macroglobulinemia.

Macroglobulinemia Pathogenesis

Although several studies in genetics have a limited number of cases, they have also demonstrated that patients with macroglobulinemia often have chromosome numbers or structural abnormalities. Common abnormal numbers are 17, 18, 19, 20, 21, 22, X and Y chromosome deletions, and an increase in the number of chromosomes 3, 4, and 12 has also been reported. Deletion of 6q21-22 occurs in 40-90% of patients with macroglobulinemia, especially in patients with family history. This region may contain several tumor suppressor genes, of which BLIMP-1 is a major regulator of lymphoid plasma cell differentiation. However, there is no recombination of lgH switch genes in macroglobulinemia, and this finding can be used to identify macroglobulinemia and lgM myeloma mainly characterized by lgH switch recombination. Macroglobulinemia Bone marrow clonal B cells are differentiated from clones of small lymphocytes with large amounts of immunoglobulin deposits on the surface to lymphoplasmic cells, and mature plasma cells containing immunoglobulin in the cytoplasm. . Sometimes clonal B cells can be detected in peripheral blood B lymphocytes, the number of which is increased in patients with drug resistance or disease progression. These clonal blood cells have the special ability to automatically differentiate into plasma cells when cultured in vitro.

Clinical manifestations of macroglobulinemia

More common in men, with an average age of 63 years. Common symptoms are weakness, weakness, weight loss, paroxysmal bleeding, and hyperviscosity syndrome. Physical examination can reveal lymphadenopathy, hepatosplenomegaly, purpura and mucosal bleeding, peripheral sensory neuropathy, Raynaud's phenomenon. Anemia is the most common clinical manifestation, and 80% of patients have anemia at the time of diagnosis. There are many reasons for anemia, including inhibition of hematopoietic function, accelerated destruction of red blood cells, and blood loss. Hemorrhage mostly manifests as nasal and oral mucosal hemorrhage, skin purpura, and visceral or cerebral hemorrhage may occur in advanced stage. Hemorrhage is caused by the formation of a complex between monoclonal lgM and multiple clotting factors or covering the surface of platelets, which affects the function of clotting factors and platelets. Hyperviscosity syndrome occurs when serum viscosity is above 4 times normal. Common symptoms include headaches, visual impairment, abnormal mental states such as confusion or dementia, and changes in consciousness can progress to coma, ataxia, or nystagmus. Congestive heart failure. Ophthalmoscope examined salivary changes in retinal veins, retinal hemorrhage, and papillary optic edema. Nervous system changes can include peripheral neuropathy, but also limited central nervous system damage. Peripheral neuropathy is the most common. The sensation and dyskinesia of the limbs are symmetrical. The sensory disorder is often more severe than the dyskinesia, and the symptoms of the lower limbs often appear first, and they are often heavier than the upper limbs. The incidence of renal insufficiency in this disease is significantly lower than in multiple myeloma, and this week's proteinuria is rare. Amyloidosis is seen in some patients.

The laboratory found that serum lgM was elevated (usually> 30mg / ml). Monoclonal lgM had light chains in 75% of the cases. Other immunoglobulins in the serum were normal or decreased. Most patients had elevated serum viscosity, but only 20%. With hyperviscosity syndrome, 80% of patients have normal cell normal pigment anemia at diagnosis, and most patients have no significant decrease in white blood cell and platelet counts at diagnosis. Tumorous B cells are monoclonal and express B-cell surface antigens (such as CD19, CD20, CD24). Tumorous B cells also often express CD5, CD10 (CALLA), CD11b, and CD9. Bone marrow biopsies are common: lymphocytes, plasma cell-like lymphocytes, or plasma cell infiltration. The prothrombin time is prolonged, and the prothrombin time and the activated partial thromboplastin time may be prolonged. Although proteinuria is common this week, only 3% of patients exceed 1g / 24h, which is of little significance. About 60% of patients with macroglobulinemia have elevated b2-microglobulin (3 mg / l). ^[1]

Macroglobulinemia diagnosis and identification

It is mainly distinguished from lgM multiple myeloma. Macroglobulinemia is mainly lymphocytes or plasma-like lymphocytes, while lgM multiple myeloma is plasma cells, and myeloma cells (primitive plasma cells, naive plasma cells, heterotypic cells) can be seen. Plasma cell). MM mainly expresses the marker of plasma cells CD38 + CD138 +, while lgM MM mainly expresses CD19 + CD20 + CD22 +. Multiple osteolytic lesions are common in MM, while macroglobulinemia is generally free of osteolytic lesions. Hypercalcemia and renal insufficiency are more common in MM and less common in macroglobulinemia. With the development of cell biology and molecular biology, analysis of MM often has t (4,14) by G band and FISH detection, ( 11,14) (14,16), 13q- and other chromosomal abnormalities, while macroglobulinemia rarely has chromosomal abnormalities.

Macroglobulinemia Treatment

The second International Symposium on Macroglobulinemia made alkylating agents (such as nitrobutyric acid mustard), nucleoside analogs, and the monoclonal antibody merawa as the ideal choice for the initial treatment of macroglobulinemia. It is particularly emphasized that when selecting first-line treatment, it is necessary to choose drugs based on whether there is blood cell reduction, whether to control the disease as soon as possible, age, and whether autotransplantation should be individualized. If autotransplantation is needed, alkylating agents or nucleoside analogs should be used with caution.

Macroglobulinemia alkylating agent as the main treatment

Take nitrobutyric acid mustard (continuous dosing regimen is onconamin 0.1mg / kg daily, intermittent dosing regimen is 0.3mg / kg, combination 7 days, once every 6 weeks). The dosage is usually adjusted according to the number of platelets and white blood cells. The main dose limiting toxicity is myelosuppression. Multiple alkylating agents have no advantage over single-drug therapy.

Macroglobulinemia nucleoside analogues

Cladribine (0.1mg / kg × 7d) or fludarabine (25mg / m2 × 5d) administered every 28 days can be used as palliative treatment or remedial treatment after the disease progress with alkylating agent. The response rate of nucleoside analogues was higher than that of alkylating agents. The main toxicity is bone marrow suppression, which increases the risk of infection.

Macroglobulinemia monoclonal antibody

A number of retrospective and prospective studies have shown that with the standard measurement of meloxa (ie, 375mg / m2 injection, once a week for 4 weeks) in the treatment of newly treated and treated patients, about 27%-35% of patients achieved a major remission . In addition, for patients with minimal efficacy, hemoglobin, platelet elevations, and enlarged lymph nodes and spleen shrinkage after treatment with meluvox. The main side effects are fever, chills, headaches, and rarely bone marrow suppression. Therefore, for those who are suitable for stem cell transplantation and high-dose chemotherapy, Metrology has become ideal. Metrology has a slow onset of action, averaging over 3 weeks. Merohua is an effective drug without bone marrow suppression, so it can be combined with chemotherapy.

Relapsed and refractory patients can re-use first-line drugs, or new targeted treatment drugs thalidomide, lenalidomide, bortezomib.

Macroglobulinemia Prognosis

Macroglobulinemia is a disease that progresses slowly with inertia, and its prognosis varies widely. Despite reports of 95% or even 10-year survival of 55%, median studies have reported median survival of only 5-7 years. Merlini et al studied 215 patients. The latest results show that factors such as serum b2-MG, hemoglobin, albumin, and age play a decisive role in the prognosis of patients with macroglobulinemia. The most common causes of death were progressive lymphoproliferation (about 50%), infection, and heart failure. A few patients died of cerebrovascular accidents, renal failure, or gastrointestinal bleeding.