Waldenström’s macroglobulinemia – wikipedia

WM was first described by Jan G. Symptoms of blood cancer in hindi Waldenström (1906–1996) in 1944 in two patients with bleeding from the nose and mouth, anemia, decreased levels of fibrinogen in the blood (hypofibrinogenemia), swollen lymph nodes, neoplastic plasma cells in bone marrow, and increased viscosity of the blood due to increased levels of a class of heavy proteins called macroglobulins. Blood cancer reasons [3]

For a time, WM was considered to be related to multiple myeloma because of the presence of monoclonal gammopathy and infiltration of the bone marrow and other organs by plasmacytoid lymphocytes. Causes of blood cancer in hindi The new World Health Organization (WHO) classification, however, places WM under the category of lymphoplasmacytic lymphomas, itself a subcategory of the indolent (low-grade) non-Hodgkin lymphomas. Cancer and white blood cell count [4] In recent years, there have been significant advances in the understanding and treatment of WM. Blood cancer diagnosis [5] Signs and symptoms [ edit ]

Signs and symptoms of WM include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums.

Colon cancer blood in stool [6] Peripheral neuropathy occurs in 10% of patients. Blood cancer report sample Lymphadenopathy and enlargement of the spleen, and/or liver are present in 30–40% of cases. Ovarian cancer blood test [7] Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma. Blood test cancer markers Causes [ edit ]

Waldenström’s macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. What is blood cancer called The most common causes are a somatic mutation in MYD88 (90% of patients) and a somatic mutation in CXCR4 (27% of patients). Liver cancer blood test [8] An association has been demonstrated with the locus 6p21.3 on chromosome 6. Blood cancer symptoms in adults [9] There is a two- to threefold increased risk of WM in people with a personal history of autoimmune diseases with autoantibodies, and a particularly elevated risk associated with liver inflammation, human immunodeficiency virus, and rickettsiosis. Blood cancer in dogs [10]

There are genetic factors, with first-degree relatives of WM patients shown to have a highly increased risk of also contracting the disease. Cancer blood transfusion [11] There is also evidence to suggest that environmental factors, including exposure to farming, pesticides, wood dust, and organic solvents, may influence the development of WM. Blood transfusion for cancer patients [12] Genetics [ edit ]

Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component. High white blood cell count cancer [13] [14] A mutation in gene MYD88 has been found to occur frequently in patients. Cancer blood clots [15] WM cells show only minimal changes in cytogenetic and gene expression studies. Prostate cancer blood in urine Their miRNA signature however differs from their normal counterpart. Cancer and blood specialists of nevada It is therefore believed that epigenetic modifications play a crucial role in the disease. Symptoms of blood cancer in hindi [16]

Comparative genomic hybridization identified the following chromosomal abnormalities: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q. Blood cancer reasons [17] FGFR3 is overexpressed. Causes of blood cancer in hindi [18] The following signalling pathways have been implicated:

The protein Src tyrosine kinase is overexpressed in Waldenström’s macroglobulinemia cells compared with control B cells. Cancer and white blood cell count [28] Inhibition of Src arrests the cell cycle at phase G 1 and has little effect on the survival of WM or normal cells.

Bone marrow tumour cells express the following antigen targets CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%). Blood cancer diagnosis [39] Pathophysiology [ edit ]

Symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomenon or cryoglobulinemia. Colon cancer blood in stool Other symptoms of WM are due to the hyperviscosity syndrome, which is present in 6–20% of patients. Blood cancer report sample [40] [41] [42] [43] This is attributed to the IgM monoclonal protein increasing the viscosity of the blood by forming aggregates to each other, binding water through their carbohydrate component and by their interaction with blood cells. Ovarian cancer blood test [44] Diagnosis [ edit ]

A diagnosis of Waldenström’s macroglobulinemia depends on a significant monoclonal IgM spike evident in blood tests and malignant cells consistent with the disease in bone marrow biopsy samples. Blood test cancer markers [45] Blood tests show the level of IgM in the blood and the presence of proteins, or tumor markers, that are the key symptoms of WM. What is blood cancer called A bone marrow biopsy provides a sample of bone marrow, usually from the back of the pelvis bone. Liver cancer blood test The sample is extracted through a needle and examined under a microscope. Blood cancer symptoms in adults A pathologist identifies the particular lymphocytes that indicate WM. Blood cancer in dogs Flow cytometry may be used to examine markers on the cell surface or inside the lymphocytes. Cancer blood transfusion [46]

Additional tests such as computed tomography (CT or CAT) scan may be used to evaluate the chest, abdomen, and pelvis, particularly swelling of the lymph nodes, liver, and spleen. Blood transfusion for cancer patients A skeletal survey can help distinguish between WM and multiple myeloma. High white blood cell count cancer [46] Anemia is typically found in 80% of patients with WM. Cancer blood clots A low white blood cell count, and low platelet count in the blood may be observed. Prostate cancer blood in urine A low level of neutrophils (a specific type of white blood cell) may also be found in some individuals with WM. Cancer and blood specialists of nevada [45]

Chemistry tests include lactate dehydrogenase (LDH) levels, uric acid levels, erythrocyte sedimentation rate (ESR), kidney and liver function, total protein levels, and an albumin-to-globulin ratio. Symptoms of blood cancer in hindi The ESR and uric acid level may be elevated. Blood cancer reasons Creatinine is occasionally elevated and electrolytes are occasionally abnormal. Causes of blood cancer in hindi A high blood calcium level is noted in approximately 4% of patients. Cancer and white blood cell count The LDH level is frequently elevated, indicating the extent of Waldenström’s macroglobulinemia–related tissue involvement. Blood cancer diagnosis Rheumatoid factor, cryoglobulins, direct antiglobulin test and cold agglutinin titre results can be positive. Colon cancer blood in stool Beta-2 microglobulin and C-reactive protein test results are not specific for Waldenström’s macroglobulinemia. Blood cancer report sample Beta-2 microglobulin is elevated in proportion to tumor mass. Ovarian cancer blood test Coagulation abnormalities may be present. Blood test cancer markers Prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen tests should be performed. What is blood cancer called Platelet aggregation studies are optional. Liver cancer blood test Serum protein electrophoresis results indicate evidence of a monoclonal spike but cannot establish the spike as IgM. Blood cancer symptoms in adults An M component with beta-to-gamma mobility is highly suggestive of Waldenström’s macroglobulinemia. Blood cancer in dogs Immunoelectrophoresis and immunofixation studies help identify the type of immunoglobulin, the clonality of the light chain, and the monoclonality and quantitation of the paraprotein. Cancer blood transfusion High-resolution electrophoresis and serum and urine immunofixation are recommended to help identify and characterize the monoclonal IgM paraprotein.

The light chain of the monoclonal protein is usually the kappa light chain. Blood transfusion for cancer patients At times, patients with Waldenström’s macroglobulinemia may exhibit more than one M protein. High white blood cell count cancer Plasma viscosity must be measured. Cancer blood clots Results from characterization studies of urinary immunoglobulins indicate that light chains ( Bence Jones protein), usually of the kappa type, are found in the urine. Prostate cancer blood in urine Urine collections should be concentrated.

Bence Jones proteinuria is observed in approximately 40% of patients and exceeds 1 g/d in approximately 3% of patients. Cancer and blood specialists of nevada Patients with findings of peripheral neuropathy should have nerve conduction studies and antimyelin associated glycoprotein serology.

2. Symptoms of blood cancer in hindi Evidence of anemia, constitutional symptoms, hyperviscosity, swollen lymph nodes, or enlargement of the liver and spleen that can be attributed to an underlying lymphoproliferative disorder. Blood cancer reasons [47] Prognosis [ edit ]

Current medical treatments result in survival of some longer than 10 years; in part this is because better diagnostic testing means early diagnosis and treatments. Causes of blood cancer in hindi Older diagnosis and treatments resulted in published reports of median survival of approximately 5 years from time of diagnosis. Cancer and white blood cell count [1] Currently, median survival is 6.5 years. Blood cancer diagnosis [48] In rare instances, WM progresses to multiple myeloma. Colon cancer blood in stool [49]

The International Prognostic Scoring System for Waldenström’s Macroglobulinemia (IPSSWM) is a predictive model to characterise long-term outcomes. Blood cancer report sample [50] [51] According to the model, factors predicting reduced survival [52] are:

The IPSSWM has been shown to be reliable. Ovarian cancer blood test [55] It is also applicable to patients on a rituximab-based treatment regimen. Blood test cancer markers [53] An additional predictive factor is elevated serum lactate dehydrogenase (LDH). What is blood cancer called [56] Treatment [ edit ]

There is no single accepted treatment for WM. Liver cancer blood test [57] There is marked variation in clinical outcome due to gaps in knowledge of the disease’s molecular basis. Blood cancer symptoms in adults Objective response rates are high (> 80%) but complete response rates are low (0–15%). Blood cancer in dogs [5] Recently, Yang et al. Cancer blood transfusion showed that the MYD88 L265P mutation induced activation of Bruton’s tyrosine kinase, the target of the drug ibrutinib. Blood transfusion for cancer patients Among previously treated patients, ibrutinib induced responses in 91% of patients, and at 2 years 69% of patients had no progression of disease and 95% were alive (Treon et al., New England Journal of Medicine 2015). High white blood cell count cancer Based on this study, the Food and Drug Administration approved ibrutinib for use in WM in 2015. Cancer blood clots [58]

WM patients are at higher risk of developing second cancers than the general population, but it is not yet clear whether treatments are contributory. Prostate cancer blood in urine [61] Watchful waiting [ edit ]

In the absence of symptoms, many clinicians will recommend simply monitoring the patient; [62] Waldenström himself stated “let well do” for such patients. Cancer and blood specialists of nevada But on occasion, the disease can be fatal, as it was to the French president Georges Pompidou, who died in office in 1974. Symptoms of blood cancer in hindi Mohammad Reza Shah Pahlavi, the Shah of Iran, also suffered from Waldenström’s macroglobulinemia, which resulted in his ill-fated trip to the United States for therapy in 1979, leading to the Iran hostage crisis. Blood cancer reasons [63] First-line [ edit ]

In 2002, a panel at the International Workshop on Waldenström’s Macroglobulinemia agreed on criteria for the initiation of therapy. Causes of blood cancer in hindi They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, and anemia due to bone marrow infiltration. Cancer and white blood cell count Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia were also suggested as indications for therapy. Blood cancer diagnosis [65]

Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Colon cancer blood in stool [66] Corticosteroids, such as prednisone, may also be used in combination. Blood cancer report sample Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease. Ovarian cancer blood test [67] Ibrutinib is another agent that has been approved for use in this condition.

When primary or secondary resistance invariably develops, salvage therapy is considered. Blood test cancer markers Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients. What is blood cancer called [72] Drug pipeline [ edit ]

As of October 2010, there have been a total of 44 clinical trials on Waldenström’s macroglobulinemia, excluding transplantation treatments. Liver cancer blood test Of these, 11 were performed on previously untreated patients, 14 in patients with relapsed or refractory Waldenström’s. Blood cancer symptoms in adults [73] A database of clinical trials investigating Waldenström’s macroglobulinemia is maintained by the National Institutes of Health in the US. Blood cancer in dogs [74] Patient stratification [ edit ]

Patients with polymorphic variants ( alleles) FCGR3A-48 and -158 were associated with improved categorical responses to rituximab-based treatments. Cancer blood transfusion [75] Epidemiology [ edit ]

WM is a rare disorder, with fewer than 1,500 cases occurring in the United States annually. Blood transfusion for cancer patients [1] The median age of onset of WM is between 60 and 65 years, with some cases occurring in late teens. High white blood cell count cancer [1] [7] Research [ edit ]

One recent investigation showed that a population of cells, lacking both B-cell and plasma cell markers, has characteristics of cancer-initiating cells in Waldenström’s macroglobulinemia. Cancer blood clots [77] See also [ edit ]