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• #1 Waldenstrom macroglobulinemia // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/waldenstrom-macroglobulinemia

  Waldenstrom macroglobulinemia grows slowly. It might not cause symptoms for years. […] When they happen, Waldenstrom macroglobulinemia symptoms may include: Fatigue. Fever. Weight loss. Night sweats. Numbness in the hands or feet. Swollen lymph nodes. A feeling of pain or fullness under the ribs on your left side, which may be caused by an enlarged spleen. Easy bruising. Bleeding nose or gums. Headache. Shortness of breath. Changes in vision. Confusion.

• #2 Symptoms of WM – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/symptoms-of-wm/

  Waldenstrom’s macroglobulinemia (WM) is slow growing and may not cause signs and symptoms for many years. One in four people (25 percent) are asymptomatic – meaning without symptoms – when they are diagnosed. Often doctors discover WM when a person has blood tests done for some other reason. […] Even after diagnosis you may not be symptomatic for many years. The most common early symptoms of WM are weakness and fatigue due to anemia. Anemia is a condition in which you lack enough red blood cells to carry adequate oxygen to your body’s organs. Other common symptoms of WM typically include: Shortness of breath, Loss of appetite and weight loss, Fever, night sweats: Similar to other lymphomas, WM can cause fevers, even when you don’t have an infection, and drenching night sweats, Numbness or tingling (a “pins and needles” sensation) in your hands or feet. This is a condition called peripheral neuropathy, Swollen lymph nodes: You may feel little lumps under the skin around your neck, groin or armpits, Swollen abdomen: This can be due to an enlarged spleen or liver, making your abdomen look swollen.

• #3 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  Waldenstrm macroglobulinemia (WM) also known as lymphoplasmacytic lymphoma is a rare, slow-growing cancer that affects your blood cells. […] WM happens when B cells (immune cells) in your bone marrow (where blood cells get made) change into cancer cells. The cancer cells copy themselves and can crowd out your normal blood cells. This can lead to low numbers of red blood cells (anemia), white blood cells (neutropenia) and platelets (thrombocytopenia). […] The cancer cells also release an abnormal protein called immunoglobulin M (IgM). Too much IgM can thicken your blood, turning it into a syrup-like liquid. This is called hyperviscosity syndrome. The thickened blood doesnt flow easily through your bodys tiny blood vessels and can cause serious symptoms. […] One in 4 people diagnosed with WM dont have symptoms. They learn they have this condition while visiting their healthcare provider for other reasons. When WM does cause symptoms, they come on slowly. Symptoms include: Weakness and fatigue, Fever, Loss of appetite, Night sweats, Weight loss, Confusion, Enlarged liver, spleen or lymph nodes, Signs of peripheral neuropathy (tingling sensation in your fingers and toes), Signs of thickened blood (nosebleeds, bleeding gums, dizziness, headaches and blurred vision).

• #4 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  Sometimes, Waldenstrom macroglobulinemia (WM) isnt causing any symptoms when its first found. Instead, its found when the person has blood tests done for some other reason. WM found this way is sometimes called asymptomatic or smoldering WM. […] When WM does cause symptoms, some of them can be like those seen with other types of non-Hodgkin lymphoma (NHL). For example, weight loss, fever, night sweats, and swollen lymph nodes can be seen in many types of NHL. […] Other WM symptoms are caused by the large amounts of abnormal IgM antibody (M protein) made by the cancer cells: In hyperviscosity syndrome, too much of the M protein in the blood can cause it to become too thick. […] When the blood gets too thick, it has trouble moving through blood vessels. This can cause problems such as poor circulation to the brain, which can lead to symptoms like those from a stroke.

• #5 12 Top Waldenström’s Macroglobulinemia Symptoms & Signs | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/waldenstroms-macroglobulinemia/waldenstroms-macroglobulinemia-symptoms.html

  In some cases, people can have Waldenstrm’s macroglobulinemia for years without showing any symptoms. When signs appear, most are caused by low blood counts or thickened blood. Symptoms vary from person to person and may include: […] These symptoms do not always mean you have Waldenstrm’s macroglobulinemia. However, it is important to discuss any symptoms with your doctor, since they may also signal other health problems.

• #6 Facts About Waldenström Macroglobulinemia | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/diseases/waldenstrom-macroglobulinemia/facts-resources.html

  Waldenstrm macroglobulinemia (WM) symptoms may be similar to symptoms caused by other conditions that are not related to cancer. Check with your physician if you feel concerned about any symptoms you have. […] Symptoms of WM may include: Weakness, Fatigue, Loss of appetite or unexplained weight loss, Swollen or enlarged lymph nodes or spleen, Peripheral neuropathy, such as numbness or tingling in your hands or feet, Unexplained fever, Heavy sweating (especially at night), Severe or widespread itchy skin. […] If IgM builds up in your blood, it may thicken your blood (a condition called hyperviscosity) and slow down the flow. This can lead to symptoms such as: Vision problems, Confusion, Dizziness, Loss of coordination, Headache, Nosebleeds or bleeding gums, Fatigue. […] In some people, the large proteins clump in cooler parts of the body like the tip of the nose, the ears and the fingers and toes blocking blood vessels and causing pain. […] Some people have no symptoms at the time of diagnosis. Instead, their disease is found when they have blood tests for another reason. This is called asymptomatic or smoldering WM.

• #7 Waldenstrom’s macroglobulinaemia (WM) – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/waldenstroms-macroglobulinaemia/

  Symptoms develop slowly with complaints of tiredness, weakness and possibly weight loss. The symptoms that a person with WM will experience can result from either the presence of the abnormal lymphocytes in the bone marrow or spleen or the result of increased antibody (IgM) in the person’s blood. […] As the numbers of abnormal lymphocytes increase, the spleen and lymph nodes “glands” will enlarge. The common lymph nodes affected are in the neck, armpits or in the groin. As the disease progresses further symptoms result from problems with blood cell production. Possible symptoms may include: anaemia, due to a lack of red cells, causing persistent tiredness, dizziness, paleness, or shortness of breath when physically active; frequent or repeated infections and slow healing, due to a lack of normal white blood cells; pain or discomfort under the ribs on the left side, due to an enlarged spleen; painless swelling of the lymph nodes (glands) in your neck, under your arms or in your groin. This is usually a result of lymphocytes accumulating in these tissues; excess antibody production leads to thickening of a person’s blood or hyperviscosity. This reduced blood circulation can lead to symptoms of headache, confusion, sleepiness and altered vision. Occasionally the antibody can damage a nerve, causing weakness. Increased antibodies can cause damage to a person’s kidneys.

• #8 What Are the Primary Clinical Manifestations of Waldenstrom’s Macroglobulinemia?

  https://www.icliniq.com/articles/blood-health/waldenstroms-macroglobulinemia

  Waldenstrom’s Macroglobulinemia (WM) presents a diverse array of clinical manifestations, reflecting both the sluggish nature of the disease and the systemic impact of elevated IgM levels. These manifestations can be grouped into several categories based on the underlying pathophysiology, including symptoms related to hyperviscosity, infiltration of organs by malignant cells, and immune dysregulation. […] Hyperviscosity syndrome is a hallmark of WM and occurs due to the excessive production of monoclonal IgM, leading to increased blood viscosity. This condition can cause a variety of neurological and ophthalmologic symptoms, such as: […] Headaches: Often described as persistent and severe, headaches are one of the most common symptoms of hyperviscosity. […] Visual Disturbances: Patients may experience blurred vision, double vision, or even vision loss due to retinal vein engorgement and hemorrhages caused by thickened blood.

• #9 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  Weakness: This is one of the most common symptoms of WM. It can be caused by anemia (too few red blood cells), which can happen when the WM cells crowd out normal cells in the bone marrow. […] Some people also feel weak when the blood thickens from the buildup of the abnormal protein. […] Fever, sweats, weight loss: WM, like other lymphomas, can cause fevers (without an infection), drenching night sweats, and weight loss (without trying). These are called B symptoms. […] Neuropathy: In some people with WM, the abnormal antibody can attack and damage nerves outside the brain. This can lead to numbness or a painful pins and needles sensation in the feet and legs, which is called neuropathy. […] In hyperviscosity syndrome, the thickened blood causes poor brain circulation, leading to problems like headache, confusion, and dizziness.

• #10 Waldenström macroglobulinemia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/897

  Waldenstrm macroglobulinemia (WM) is a rare indolent B-cell lymphoma that most commonly occurs in older white men. […] Anemia (due to marrow infiltration), fatigue, and anorexia are the most common clinical features. […] Lymphadenopathy, splenomegaly, and hyperviscosity (which can lead to skin and mucosal bleeding, thrombosis, retinopathy with visual disturbances, and neurologic symptoms such as headache, dizziness, and vertigo) are uncommon, but they are important clinical manifestations that require urgent treatment. […] Clinical manifestations are most commonly related to bone marrow infiltration by malignant cells (e.g., anemia, thrombocytopenia, pancytopenia). […] They are less commonly related to organ infiltration (e.g., splenomegaly, hepatomegaly, and lymphadenopathy) and abnormal IgM properties and/or organ deposition (e.g., hyperviscosity syndrome, polyneuropathy, cryoglobulinemia, cold agglutinin hemolytic anemia, bleeding from the nose and gums, purpura, thrombosis [e.g., stroke, angina, myocardial infarction, pulmonary embolism, deep vein thrombosis], and kidney disease). […] WM can transform to aggressive high-grade lymphomas.

• #11 Waldenström macroglobulinaemia (WM) symptoms and diagnosis | Blood Cancer UK

  https://bloodcancer.org.uk/understanding-blood-cancer/lymphoma/waldenstrom-macroglobulinaemia/wm-symptoms-diagnosis/

  People with WM may also have certain symptoms known as B symptoms, which can include unexplained weight loss, heavy sweating and fever (high temperature). […] Large amounts of IgM in the blood can cause damage to your nerves, known as neuropathy. This can lead to pain or numbness, often in the legs and feet.

• #12 Waldenström macroglobulinemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/

  Waldenström macroglobulinemia usually begins in a person’s sixties and is a slow-growing (indolent) cancer. […] The most common signs and symptoms to first appear in people with Waldenström macroglobulinemia are weakness and extreme tiredness (fatigue) caused by a shortage of red blood cells (anemia). Affected individuals can also experience general symptoms such as fever, night sweats, and weight loss. Some people with Waldenström macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). […] Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy).

• #13 Waldenstrom Macroglobulinemia | Condition | UAMS Health

  https://uamshealth.com/condition/waldenstrom-macroglobulinemia/

  The overgrowth of B cell lymphocytes in Waldenstroms inhibits the growth of normal cells, resulting in low numbers of red blood cells, white blood cells, and platelets, which can lead to fatigue, frequent infections and excessive bruising or bleeding. […] Symptoms of Waldenstroms can include: Fatigue, Bleeding of the gums, Nose bleeding, Blurred or decreased vision, Dizziness, headache, confusion, Easy bruising of the skin, Numbness or tingling in the hands or feet, Weight loss, Fever and night sweats, Swollen lymph nodes, Heart palpitations, Swelling in the feet and legs, Abdominal pain. […] It is possible for a person to be asymptomatic and yet, based on high levels of IgM, be diagnosed with Waldenstroms. Sometimes Waldenstroms produces few symptoms and develops slowly.

• #14 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  Sometimes, Waldenstrom macroglobulinemia (WM) isnt causing any symptoms when its first found. Instead, its found when the person has blood tests done for some other reason. WM found this way is sometimes called asymptomatic or smoldering WM. […] When WM does cause symptoms, some of them can be like those seen with other types of non-Hodgkin lymphoma (NHL). For example, weight loss, fever, night sweats, and swollen lymph nodes can be seen in many types of NHL. […] Other WM symptoms are caused by the large amounts of abnormal IgM antibody (M protein) made by the cancer cells: In hyperviscosity syndrome, too much of the M protein in the blood can cause it to become too thick. […] When the blood gets too thick, it has trouble moving through blood vessels. This can cause problems such as poor circulation to the brain, which can lead to symptoms like those from a stroke.

• #15 About Waldenström’s macroglobulinaemia (WM) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/lymphoma/non-hodgkin/types/waldenstroms-macroglobulinaemia

  Waldenstrms macroglobulinaemia (WM) usually develops over a long period of time. Some people have no symptoms. It can be discovered when blood tests are done for some other reason. […] Symptoms can be caused by lymphoma cells building up in the bone marrow. The lymphoma cells take up space, which makes it difficult for the bone marrow to make enough normal blood cells. […] The most common symptoms are: feeling weak and tired (fatigue), looking very pale or feeling breathless because of a lack of red blood cells (anaemia), repeated infections because of a lack of healthy white blood cells (which help fight infection), bruising or bleeding easily, heavy, drenching night sweats, weight loss. […] Some people have symptoms caused by high levels of IgM in the blood. The blood becomes thicker and more slow-moving than normal. This can cause: headaches, confusion, nosebleeds, blurred vision.

• #16 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  Waldenstrm macroglobulinemia (WM) also known as lymphoplasmacytic lymphoma is a rare, slow-growing cancer that affects your blood cells. […] WM happens when B cells (immune cells) in your bone marrow (where blood cells get made) change into cancer cells. The cancer cells copy themselves and can crowd out your normal blood cells. This can lead to low numbers of red blood cells (anemia), white blood cells (neutropenia) and platelets (thrombocytopenia). […] The cancer cells also release an abnormal protein called immunoglobulin M (IgM). Too much IgM can thicken your blood, turning it into a syrup-like liquid. This is called hyperviscosity syndrome. The thickened blood doesnt flow easily through your bodys tiny blood vessels and can cause serious symptoms. […] One in 4 people diagnosed with WM dont have symptoms. They learn they have this condition while visiting their healthcare provider for other reasons. When WM does cause symptoms, they come on slowly. Symptoms include: Weakness and fatigue, Fever, Loss of appetite, Night sweats, Weight loss, Confusion, Enlarged liver, spleen or lymph nodes, Signs of peripheral neuropathy (tingling sensation in your fingers and toes), Signs of thickened blood (nosebleeds, bleeding gums, dizziness, headaches and blurred vision).

• #17 Waldenström’s macroglobulinaemia – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/897

  Waldenstrm’s macroglobulinaemia (WM) is a rare indolent B-cell lymphoma that most commonly occurs in older white men. […] Anaemia (due to marrow infiltration), fatigue, and anorexia are the most common clinical features. […] Lymphadenopathy, splenomegaly, and hyperviscosity (which can lead to skin and mucosal bleeding, thrombosis, retinopathy with visual disturbances, and neurological symptoms such as headache, dizziness, and vertigo) are uncommon, but they are important clinical manifestations that require urgent treatment. […] Clinical manifestations are most commonly related to bone marrow infiltration by malignant cells (e.g., anaemia, thrombocytopenia, pancytopenia). […] They are less commonly related to organ infiltration (e.g., splenomegaly, hepatomegaly, and lymphadenopathy) and abnormal IgM properties and/or organ deposition (e.g., hyperviscosity syndrome, polyneuropathy, cryoglobulinaemia, cold agglutinin haemolytic anaemia, bleeding from the nose and gums, purpura, thrombosis [e.g., stroke, angina, myocardial infarction, pulmonary embolism, deep vein thrombosis], and kidney disease). […] WM can transform to aggressive high-grade lymphomas.

• #18 Waldenström’s Macroglobulinemia | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/waldenstroms-macroglobulinemia.html

  Waldenstrm’s macroglobulinemia is a type of lymphoma. It is a low-grade, or indolent, form of the cancer, meaning it spreads slowly and is usually controlled easily when diagnosed early. […] In Waldenstrms, the body produces too much of a protein called immunoglobulin M (IgM). When this protein builds up, the blood can become thick. This makes it difficult for the blood to move through the blood vessels. […] Waldenstrm’s macroglobulinemia cells can grow in the liver, spleen and lymph nodes, causing them to swell. They also can grow in the bone marrow, crowding out normal cells. When this happens, levels of red blood cells (which carry oxygen through the body) or white blood cells (which help the body fight infection) may fall. Levels of platelets, a type of blood cell needed to stop bleeding, also may fall.

• #19 Waldenstrom Macroglobulinemia | Lymphoma Research Foundation

  https://www.lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/wm/

  Waldenstrm macroglobulinemia (WM), which is a subtype of lymphoplasmacytic lymphoma, is a rare indolent (slow-growing) B-cell lymphoma that occurs in less than two percent of patients with non-Hodgkin lymphoma (NHL). […] Lymphoma cells in the bone marrow grow and block normal cells, making it difficult for the bone marrow to produce normal amounts of red and white blood cells. This can result in anemia (low levels of red blood cells), neutropenia (low levels of white blood cells called neutrophils), and thrombocytopenia (low levels of platelets). […] Patients with WM have a high level of a protein called immunoglobulin M (IgM) in their blood, which can cause hyperviscosity (thickening of the blood).

• #20 Waldenström macroglobulinemia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/897

  Waldenstrm macroglobulinemia (WM) is a rare indolent B-cell lymphoma that most commonly occurs in older white men. […] Anemia (due to marrow infiltration), fatigue, and anorexia are the most common clinical features. […] Lymphadenopathy, splenomegaly, and hyperviscosity (which can lead to skin and mucosal bleeding, thrombosis, retinopathy with visual disturbances, and neurologic symptoms such as headache, dizziness, and vertigo) are uncommon, but they are important clinical manifestations that require urgent treatment. […] Clinical manifestations are most commonly related to bone marrow infiltration by malignant cells (e.g., anemia, thrombocytopenia, pancytopenia). […] They are less commonly related to organ infiltration (e.g., splenomegaly, hepatomegaly, and lymphadenopathy) and abnormal IgM properties and/or organ deposition (e.g., hyperviscosity syndrome, polyneuropathy, cryoglobulinemia, cold agglutinin hemolytic anemia, bleeding from the nose and gums, purpura, thrombosis [e.g., stroke, angina, myocardial infarction, pulmonary embolism, deep vein thrombosis], and kidney disease). […] WM can transform to aggressive high-grade lymphomas.

• #21 Waldenstrom’s Macroglobulinemia | University of Iowa Health Care

  https://uihc.org/health-topics/waldenstroms-macroglobulinemia

  Waldenstrom’s macroglobulinemia is a rare disorder that causes the production of abnormal B-lymphocytes, white blood cells. Symptoms are due to accumulation of abnormal lymphocytes in the bone marrow or the abnormal protein in the blood. The former causes anemia, low white blood count or low platelets. These cells also produce too much macroglobulin, a protein that both thickens the blood and coats the platelet cells. The thickened blood may clot in the fingers and toes, causing numbness, or in the brain, causing dizziness and confusion. The covered platelet cells may not work right, resulting in bleeding and easy bruising. […] The following symptoms will require prompt attention: […] easy bruising […] bleeding for no apparent reason […] unusually heavy or prolonged bleeding […] severe headache or visual changes

• #22 Symptoms of WM – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/symptoms-of-wm/

  There are several complications of WM that can happen to some people and may cause symptoms. These complications include: Hyperviscosity syndrome: With WM, your body produces abnormally high levels of the antibody IgM. Having high levels of IgM in your blood makes it thick – or viscous – impairing blood flow, especially through small blood vessels. […] Some of the more common symptoms of hyperviscosity syndrome are: Headache, Dizziness, Confusion, Bleeding from the nose and gums, Changes in vision, such as blurriness, double-vision or blind spots. […] Symptoms of cold agglutinin disease may include: Dark urine, Fatigue, Shortness of breath, Jaundice (yellow skin and eyes), Painful fingers and toes when exposed to the cold. […] Cryoglobulinemia can cause symptoms such as: Blueness and/or pain of your hands or feet in cold temperatures, Purplish or red-brown skin lesions (called purpura), Skin ulcers and gangrene, Swollen ankles and legs, Joint pain. […] Symptoms of amyloidosis may include: Fatigue and weakness, Shortness of breath, Irregular heartbeat, Swollen tongue, Difficulty swallowing, Foamy urine, Diarrhea, Joint pain.

• #23 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  Sometimes, Waldenstrom macroglobulinemia (WM) isnt causing any symptoms when its first found. Instead, its found when the person has blood tests done for some other reason. WM found this way is sometimes called asymptomatic or smoldering WM. […] When WM does cause symptoms, some of them can be like those seen with other types of non-Hodgkin lymphoma (NHL). For example, weight loss, fever, night sweats, and swollen lymph nodes can be seen in many types of NHL. […] Other WM symptoms are caused by the large amounts of abnormal IgM antibody (M protein) made by the cancer cells: In hyperviscosity syndrome, too much of the M protein in the blood can cause it to become too thick. […] When the blood gets too thick, it has trouble moving through blood vessels. This can cause problems such as poor circulation to the brain, which can lead to symptoms like those from a stroke.

• #24 Facts About Waldenström Macroglobulinemia | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/diseases/waldenstrom-macroglobulinemia/facts-resources.html

  Waldenstrm macroglobulinemia (WM) symptoms may be similar to symptoms caused by other conditions that are not related to cancer. Check with your physician if you feel concerned about any symptoms you have. […] Symptoms of WM may include: Weakness, Fatigue, Loss of appetite or unexplained weight loss, Swollen or enlarged lymph nodes or spleen, Peripheral neuropathy, such as numbness or tingling in your hands or feet, Unexplained fever, Heavy sweating (especially at night), Severe or widespread itchy skin. […] If IgM builds up in your blood, it may thicken your blood (a condition called hyperviscosity) and slow down the flow. This can lead to symptoms such as: Vision problems, Confusion, Dizziness, Loss of coordination, Headache, Nosebleeds or bleeding gums, Fatigue. […] In some people, the large proteins clump in cooler parts of the body like the tip of the nose, the ears and the fingers and toes blocking blood vessels and causing pain. […] Some people have no symptoms at the time of diagnosis. Instead, their disease is found when they have blood tests for another reason. This is called asymptomatic or smoldering WM.

• #25 What is Waldenström’s macroglobulinaemia? : University College London Hospitals NHS Foundation Trust

  https://www.uclh.nhs.uk/our-services/find-service/cancer-services/waldenstroms-macroglobulinemia-1/what-waldenstroms-macroglobulinaemia

  WM often develops over a long period of time and many people have no symptoms at all. This means that sometimes the condition is found by chance while having investigations for another condition or on a routine blood test. […] Symptoms of WM can be: tiredness, a tendency to develop infections, a tendency to bruise or bleed easily, fevers, night sweats, weight loss. […] If there is a large amount of IgM protein in the bloodstream in WM, this can make the blood thicker and more slow-flowing than normal. This is called hyperviscosity. […] This can cause symptoms such as: nosebleeds, blurring or loss of vision, dizziness or headaches, drowsiness, poor concentration or confusion, shortness of breath due to heart or lung failure. […] The IgM protein can also affect the small nerves in the hands and feet and this can cause neuropathy (numbness or tingling) affecting the fingers and toes.

• #26 What Are the Primary Clinical Manifestations of Waldenstrom’s Macroglobulinemia?

  https://www.icliniq.com/articles/blood-health/waldenstroms-macroglobulinemia

  Waldenstrom’s Macroglobulinemia (WM) presents a diverse array of clinical manifestations, reflecting both the sluggish nature of the disease and the systemic impact of elevated IgM levels. These manifestations can be grouped into several categories based on the underlying pathophysiology, including symptoms related to hyperviscosity, infiltration of organs by malignant cells, and immune dysregulation. […] Hyperviscosity syndrome is a hallmark of WM and occurs due to the excessive production of monoclonal IgM, leading to increased blood viscosity. This condition can cause a variety of neurological and ophthalmologic symptoms, such as: […] Headaches: Often described as persistent and severe, headaches are one of the most common symptoms of hyperviscosity. […] Visual Disturbances: Patients may experience blurred vision, double vision, or even vision loss due to retinal vein engorgement and hemorrhages caused by thickened blood.

• #27 Waldenstrom’s macroglobulinaemia (WM) – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/waldenstroms-macroglobulinaemia/

  Waldenstrom’s macroglobulinaemia (WM) is an uncommon type of blood cancer. WM (lymphoplasmacytic lymphoma) is a disorder that has features in common with indolent non-Hodgkin lymphoma and with myeloma. WM more closely resembles indolent lymphoma in its progression as a disease. […] In WM, abnormal lymphoma and plasma cells produce excess amounts of a particular antibody (or immunoglobulin) called IgM. The “M” in IgM stands for macroglobulin and is where the naming macroglobinaemia is derived from. Over time IgM builds up in the bone marrow, spleen and blood, causing it to become thicker and blood flow to various body organs may be impaired. This complication occurs in approximately 10-30% of people with this disease. Symptoms may include changes in vision, headaches, hearing loss, abnormal bleeding and confusion. People can also experience lethargy and fatigue, and are at increased risk of infection.

• #28 Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies

  https://www.mdpi.com/1422-0067/23/19/11145

  Waldenströms macroglobulinemia is an indolent, B-cell lymphoma without a known cure. […] Approximately 75% of WM patients have symptoms at the time of diagnosis and anemia is common, as WM cell growth in the bone marrow progresses. Hyperviscosity syndrome, caused by abnormal IgM secretion and accumulation in the blood, occurs in 10–30% of patients and may be life-threatening. […] WM has an associated precursor disease, monoclonal gammopathy of undetermined significance (MGUS) of IgM type. IgM MGUS is defined by a serum concentration of 3 g/dL or less of IgM paraprotein, the absence of proliferation of plasma cells, and a population of 10% or less of bone marrow plasma cells. MGUS can progress to WM, and typically does so at a rate of 1% per year, indicating the importance of understanding IgM MGUS.

• #29 Waldenström Macroglobulinemia: Possible Effects – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/waldenstrom-macroglobulinemia-possible-effects/

  This is the third part of our series about the condition based on our patient booklet Fast Facts for Patients: Waldenstrm Macroglobulinemia. This article addresses some of the possible effects of Waldenstrm macroglobulinemia (WM). […] The effects of WM vary from person to person. You may experience some or none of these effects. […] Symptoms include bleeding from the nose and mouth, headaches, blurred or loss of vision and dizziness. These symptoms are more likely to occur if your IgM level is over 40 g/L. Your doctor will recommend treatment if you have symptoms. […] The symptoms are varied, but may include headaches, seizures, weakness of the facial or limb muscles, double vision, personality change and memory loss. […] The affected areas have poor blood circulation, especially when it is cold: color changes and ulcers may develop as the skin breaks down.

• #30 Diagnosis and Risk Stratification in Waldenström Macroglobulinemia in: Journal of the National Comprehensive Cancer Network Volume 22 Issue 7 (2024)

  https://jnccn.org/abstract/journals/jnccn/22/7/article-e247024.xml

  Waldenstrm macroglobulinemia (WM) is a B-cell lymphoma characterized by the presence of bone marrow lymphoplasmacytic infiltration and circulating monoclonal immunoglobulin M protein. The clinical presentation of WM is variable, ranging from gradually progressive cytopenias, organomegaly, fatigue, B symptoms, and peripheral neuropathy to the more emergent presentation with symptomatic hyperviscosity, cryoglobulinemia, hemolytic anemia associated symptoms, acquired von Willebrand disease or acquired hemophilia associated bleeding. Approximately 1 in 5 patients with WM are asymptomatic at diagnosis and classified as having smoldering WM, not requiring WM-directed therapy. […] Fatigue, the most common presenting feature, is largely attributable to anemia, but in the setting of high levels of circulating cytokines, it can be disproportionately more pronounced than the degree of anemia. Cytopenias may result from increasing marrow LPL involvement, but are manifestations of autoimmune phenomena, rarely, or can result from splenomegaly, with hypersplenism. Peripheral neuropathy is noted in up to 20% of patients, most commonly due to IgM binding to myelin-associated glycoprotein (anti-MAG) and less commonly due to anti-sulfatide or anti-ganglioside antibodies or to deposition of amyloid in nerves.

• #31 What Are the Primary Clinical Manifestations of Waldenstrom’s Macroglobulinemia?

  https://www.icliniq.com/articles/blood-health/waldenstroms-macroglobulinemia

  Fever: Although less common, unexplained fevers may be a part of the symptom complex in WM. […] Peripheral neuropathy is a significant and often debilitating manifestation of WM. It is typically characterized by: […] Numbness and Tingling: Patients may report a „pins and needles” sensation, usually starting in the extremities and progressing over time. […] Weakness: Muscle weakness, particularly in the hands and feet, can make mobility and daily tasks difficult. […] Pain: Neuropathic pain, described as burning or shooting, may also be present and can be resistant to conventional pain management strategies. […] The infiltration of malignant lymphoplasmacytic cells into various organs can lead to: […] Enlargement of lymph nodes is a common finding, particularly in the neck, armpits, or groin. The swollen nodes are usually painless but can cause discomfort due to their size.

• #32 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  Weakness: This is one of the most common symptoms of WM. It can be caused by anemia (too few red blood cells), which can happen when the WM cells crowd out normal cells in the bone marrow. […] Some people also feel weak when the blood thickens from the buildup of the abnormal protein. […] Fever, sweats, weight loss: WM, like other lymphomas, can cause fevers (without an infection), drenching night sweats, and weight loss (without trying). These are called B symptoms. […] Neuropathy: In some people with WM, the abnormal antibody can attack and damage nerves outside the brain. This can lead to numbness or a painful pins and needles sensation in the feet and legs, which is called neuropathy. […] In hyperviscosity syndrome, the thickened blood causes poor brain circulation, leading to problems like headache, confusion, and dizziness.

• #33 About Waldenström’s macroglobulinaemia (WM) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/lymphoma/non-hodgkin/types/waldenstroms-macroglobulinaemia

  Sometimes people develop numbness or tingling in their hands and feet. They may also have problems with their balance. This is due to nerve damage (neuropathy) caused by the abnormal protein in the blood. […] WM is a low-grade lymphoma and normally develops slowly. Rarely it can change (transform) to a high-grade lymphoma.

• #34 How to manage Waldenstrom’s macroglobulinemia | Leukemia

  https://www.nature.com/articles/leu201336

  Treatment options should be adapted to the aggressiveness of the neuropathy and the dynamics of progression. Watch and wait is recommended for non-disabling neuropathy, rituximab monotherapy can be used in disabling, but slowly progressive neuropathy, as rituximab single-agent-induced improvements develop slowly with a median clinical response time of 9 months, observed in 30-80% of patients. In rapidly progressive and disabling neuropathy, rapid control of the disease is needed. In this case, the combination of rituximab/chemotherapy (for example, cyclophosphamide, purine analogs) is recommended. […] In case of hyperviscosity or interaction of the monoclonal protein with coagulation factors, mainly factor VIII Willebrand and fibrinogen, plasmapheresis should be started, followed by rituximab/chemotherapy regimens, such as R-CHOP, R-bendamustine, rituximab/purine analogs or R-bortezomib, ensuring rapid clinical response.

• #35 Waldenström macroglobulinemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/

  Waldenström macroglobulinemia usually begins in a person’s sixties and is a slow-growing (indolent) cancer. […] The most common signs and symptoms to first appear in people with Waldenström macroglobulinemia are weakness and extreme tiredness (fatigue) caused by a shortage of red blood cells (anemia). Affected individuals can also experience general symptoms such as fever, night sweats, and weight loss. Some people with Waldenström macroglobulinemia develop a loss of sensation and weakness in the limbs (peripheral neuropathy). […] Other features of Waldenström macroglobulinemia are due to the accumulation of lymphoplasmacytic cells in different tissues. For example, accumulation of these cells can lead to an enlarged liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy).

• #36 What Are the Primary Clinical Manifestations of Waldenstrom’s Macroglobulinemia?

  https://www.icliniq.com/articles/blood-health/waldenstroms-macroglobulinemia

  Fever: Although less common, unexplained fevers may be a part of the symptom complex in WM. […] Peripheral neuropathy is a significant and often debilitating manifestation of WM. It is typically characterized by: […] Numbness and Tingling: Patients may report a „pins and needles” sensation, usually starting in the extremities and progressing over time. […] Weakness: Muscle weakness, particularly in the hands and feet, can make mobility and daily tasks difficult. […] Pain: Neuropathic pain, described as burning or shooting, may also be present and can be resistant to conventional pain management strategies. […] The infiltration of malignant lymphoplasmacytic cells into various organs can lead to: […] Enlargement of lymph nodes is a common finding, particularly in the neck, armpits, or groin. The swollen nodes are usually painless but can cause discomfort due to their size.

• #37 Symptoms of WM – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/symptoms-of-wm/

  Waldenstrom’s macroglobulinemia (WM) is slow growing and may not cause signs and symptoms for many years. One in four people (25 percent) are asymptomatic – meaning without symptoms – when they are diagnosed. Often doctors discover WM when a person has blood tests done for some other reason. […] Even after diagnosis you may not be symptomatic for many years. The most common early symptoms of WM are weakness and fatigue due to anemia. Anemia is a condition in which you lack enough red blood cells to carry adequate oxygen to your body’s organs. Other common symptoms of WM typically include: Shortness of breath, Loss of appetite and weight loss, Fever, night sweats: Similar to other lymphomas, WM can cause fevers, even when you don’t have an infection, and drenching night sweats, Numbness or tingling (a “pins and needles” sensation) in your hands or feet. This is a condition called peripheral neuropathy, Swollen lymph nodes: You may feel little lumps under the skin around your neck, groin or armpits, Swollen abdomen: This can be due to an enlarged spleen or liver, making your abdomen look swollen.

• #38 Waldenstrom’s macroglobulinaemia (WM) – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/waldenstroms-macroglobulinaemia/

  Symptoms develop slowly with complaints of tiredness, weakness and possibly weight loss. The symptoms that a person with WM will experience can result from either the presence of the abnormal lymphocytes in the bone marrow or spleen or the result of increased antibody (IgM) in the person’s blood. […] As the numbers of abnormal lymphocytes increase, the spleen and lymph nodes “glands” will enlarge. The common lymph nodes affected are in the neck, armpits or in the groin. As the disease progresses further symptoms result from problems with blood cell production. Possible symptoms may include: anaemia, due to a lack of red cells, causing persistent tiredness, dizziness, paleness, or shortness of breath when physically active; frequent or repeated infections and slow healing, due to a lack of normal white blood cells; pain or discomfort under the ribs on the left side, due to an enlarged spleen; painless swelling of the lymph nodes (glands) in your neck, under your arms or in your groin. This is usually a result of lymphocytes accumulating in these tissues; excess antibody production leads to thickening of a person’s blood or hyperviscosity. This reduced blood circulation can lead to symptoms of headache, confusion, sleepiness and altered vision. Occasionally the antibody can damage a nerve, causing weakness. Increased antibodies can cause damage to a person’s kidneys.

• #39 Waldenström macroglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/Waldenstr%C3%B6m_macroglobulinemia

  Signs and symptoms of Waldenstrm macroglobulinemia include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30-40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma. […] Symptoms including blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomena or cryoglobulinemia. Other symptoms of Waldenstrm macroglobulinemia are due to hyperviscosity syndrome, which is present in 6-20% of patients. This is attributed to the IgM monoclonal protein molecules 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.

• #40 What Causes Waldenström Macroglobulinemia and How Will It Affect Me? – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/what-causes-waldenstrom-macroglobulinemia-and-how-will-it-affect-me/

  In about a quarter of patients with WM, lymph nodes and/or the spleen may enlarge; you might notice swollen glands. Rarely, a swollen spleen can be uncomfortable or painful. […] LPL cells may collect in body cavities, causing soft tissue masses (lumps) or a buildup of fluid in the chest (pleural effusion). Rarely, the cells may build-up in the skeleton, causing bone pain. If these symptoms appear, the diagnosis is confirmed by taking scans and analyzing samples of tissue from a biopsy.

• #41 Symptoms of WM – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/symptoms-of-wm/

  There are several complications of WM that can happen to some people and may cause symptoms. These complications include: Hyperviscosity syndrome: With WM, your body produces abnormally high levels of the antibody IgM. Having high levels of IgM in your blood makes it thick – or viscous – impairing blood flow, especially through small blood vessels. […] Some of the more common symptoms of hyperviscosity syndrome are: Headache, Dizziness, Confusion, Bleeding from the nose and gums, Changes in vision, such as blurriness, double-vision or blind spots. […] Symptoms of cold agglutinin disease may include: Dark urine, Fatigue, Shortness of breath, Jaundice (yellow skin and eyes), Painful fingers and toes when exposed to the cold. […] Cryoglobulinemia can cause symptoms such as: Blueness and/or pain of your hands or feet in cold temperatures, Purplish or red-brown skin lesions (called purpura), Skin ulcers and gangrene, Swollen ankles and legs, Joint pain. […] Symptoms of amyloidosis may include: Fatigue and weakness, Shortness of breath, Irregular heartbeat, Swollen tongue, Difficulty swallowing, Foamy urine, Diarrhea, Joint pain.

• #42 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  The high levels of abnormal antibody in WM can slow the bodys normal antibody production. This makes it harder for the body to fight infections. […] In some people with WM, the buildup of the M protein in the intestines can lead to problems such as diarrhea, poor absorption of vitamins, or gastrointestinal bleeding (seen as blood in the stools or dark stools). […] In people with cryoglobulins, exposure to cold temperatures can lead to pain, itching, a bluish color, or even sores on the tip of the nose, ears, fingers, or toes due to reduced blood flow to these areas.

• #43 Lymphoplasmacytic Lymphoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513356/

  Most Waldenstrom macroglobulinemia patients have monoclonal IgM. A minority can have both IgM and IgG. Waldenstrom macroglobulinemia patients can present with hyperviscosity symptoms (30%), autoimmune hemolysis (20%), coagulopathy, and/or diarrhea. Symptoms related to hyperviscosity include visual impairment, neurologic symptoms (neuropathy), bleeding, new-onset headaches, blurred vision, and cryoglobulinemia leading to Raynaud phenomena and cold urticaria. The neuropathy is sensory and affects more the feet than hands in a bilaterally symmetric pattern. The autoimmune hemolysis is due to cold agglutinins (IgM antibodies that bind at less than 37 C). […] The median survival of lymphoplasmacytic lymphoma patients is approximately five years. About 40% of patients survive for ten years or more. Typically, the cause of death is more due to advance age-associated comorbidities than WM.

• #44 Macroglobulinemia – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/plasma-cell-disorders/macroglobulinemia

  Most patients are asymptomatic, but some present with anemia or manifestations of hyperviscosity syndrome (eg, fatigue, weakness, skin deposits, skin and mucosal bleeding, visual disturbances, headache, symptoms of peripheral neuropathy, and other changing neurologic manifestations). An increased plasma volume can precipitate heart failure. Cold sensitivity, Raynaud syndrome, or recurring bacterial infections may occur. […] Clinical manifestations of macroglobulinemia include bleeding, recurrent infections, generalized adenopathy, anemia, neurologic symptoms, and hepatosplenomegaly. Less commonly, patients develop hyperviscosity due to the large amounts of high molecular weight monoclonal IgM proteins circulating in plasma, but most patients do not develop problems related to high IgM levels.

• #45 Symptoms of WM – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/symptoms-of-wm/

  There are several complications of WM that can happen to some people and may cause symptoms. These complications include: Hyperviscosity syndrome: With WM, your body produces abnormally high levels of the antibody IgM. Having high levels of IgM in your blood makes it thick – or viscous – impairing blood flow, especially through small blood vessels. […] Some of the more common symptoms of hyperviscosity syndrome are: Headache, Dizziness, Confusion, Bleeding from the nose and gums, Changes in vision, such as blurriness, double-vision or blind spots. […] Symptoms of cold agglutinin disease may include: Dark urine, Fatigue, Shortness of breath, Jaundice (yellow skin and eyes), Painful fingers and toes when exposed to the cold. […] Cryoglobulinemia can cause symptoms such as: Blueness and/or pain of your hands or feet in cold temperatures, Purplish or red-brown skin lesions (called purpura), Skin ulcers and gangrene, Swollen ankles and legs, Joint pain. […] Symptoms of amyloidosis may include: Fatigue and weakness, Shortness of breath, Irregular heartbeat, Swollen tongue, Difficulty swallowing, Foamy urine, Diarrhea, Joint pain.

• #46 Waldenström macroglobulinemia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/waldenstrom-macroglobulinemia/

  Several other signs and symptoms of Waldenström macroglobulinemia are related to the excess amounts of IgM. Increased IgM can thicken blood and impair circulation, causing a condition known as hyperviscosity syndrome. […] The IgM protein, along with another protein called amyloid, can build up in organs and interfere with their normal function. This buildup causes a condition called amyloidosis. Organs that are typically affected by amyloidosis include the heart, kidneys, liver or spleen. Affected individuals can experience weakness, fatigue, shortness of breath, irregular heartbeat, or joint pain.

• #47 Signs and Symptoms of Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/detection-diagnosis-staging/signs-symptoms.html

  It can also cause symptoms like those seen with a stroke, including slurred speech and weakness on one side of the body. […] High levels of abnormal antibody can damage blood vessels, which can lead to problems like nosebleeds and bleeding gums. […] High levels of the M protein can damage the kidneys directly or through the development of amyloidosis. […] When the kidneys dont work well, excess salt, fluid, and body waste products stay in the blood. This can cause symptoms like weakness, trouble breathing, and fluid buildup in body tissues. […] High levels of the M protein can damage heart tissue directly or through the development of amyloidosis, in which the protein builds up in the heart muscle. […] This weakens the heart, affecting its ability to pump blood. […] Symptoms can include heart palpitations, feeling tired and weak, cough, shortness of breath, rapid weight gain, and swelling in the feet and legs.

• #48 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  In severe cases, WM can cause complications, including: Amyloidosis. This condition happens when faulty proteins build up in organs like your heart, lungs and kidneys. Cryoglobulinemia. This condition happens when certain blood proteins that react to cold conditions gather in clumps in your hands and feet. This can cause pain and turn your hands and feet blue or white (cyanosis). […] As there isnt a cure for this condition, the best treatment is one that relieves symptoms with the least amount of side effects. […] Your healthcare provider will work with you to customize treatment. Options for WM include: Watchful waiting. Your provider may not start treatment if you dont have symptoms. Some people with WM dont need treatment for years. Plasmapheresis (plasma exchange). Providers use a machine to filter abnormal IgM from your plasma, the liquid part of your blood. They return the plasma to your bloodstream. Providers use this treatment to ease symptoms caused by thickening blood. Immunotherapy. This treatment uses your bodys immune system to destroy or slow the growth of WM cells. Providers commonly prescribe rituximab (Rituxan) alone or with chemotherapy.

• #49 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  Waldenstrm macroglobulinemia, one of the malignant monoclonal gammopathies, is a chronic, indolent, lymphoproliferative disorder. It is characterized by the presence of a high level of a macroglobulin (immunoglobulin M [IgM]), elevated serum viscosity, and the presence of a lymphoplasmacytic infiltrate in the bone marrow. The clinical manifestations of Waldenstrm macroglobulinemia result from the presence of the IgM paraprotein and malignant lymphoplasmacytic cell infiltration of the bone marrow and other tissue sites. The clinical presentation is similar to that of multiple myeloma except that (1) organomegaly is common in Waldenstrm macroglobulinemia and is uncommon in multiple myeloma and (2) lytic bony disease and renal disease are uncommon in Waldenstrm macroglobulinemia but are common in multiple myeloma. Waldenstrm macroglobulinemia is not curable, but a number of therapies have shown activity in the disease. For asymptomatic patients without end-organ damage, management consists of careful observation. In symptomatic patients, monotherapy with rituximab is the usual choice, especially for nonbulky disease. Bulky symptomatic disease may require combination regimens, such as chemotherapy. Hyperviscosity syndrome may mandate emergency plasmapheresis. Complications of Waldenstrm macroglobulinemia include the following: Hyperviscosity syndrome, visual disturbances secondary to hyperviscosity syndrome, diarrhea and malabsorption secondary to gastrointestinal (GI) involvement, kidney disease (less common), amyloidosis of the heart, kidney, liver, lungs, and joints, bleeding manifestations secondary to platelet dysfunction and coagulation factor and fibrinogen abnormalities due to interaction with plasma IgM, peripheral neuropathy, Raynaud phenomenon secondary to cryoglobulinemia, increased predisposition to infection due to B-cell dysfunction (disease related) or T-cell dysfunction (therapy related, particularly after nucleoside analogues), cardiac failure, increased incidence of lymphomas, myelodysplasia, and leukemias. The clinical manifestations of this disorder result from 2 important factors. First, secretion of the IgM paraprotein leads to hyperviscosity and vascular complications because of physical, chemical, and immunologic properties of the paraprotein. These complications include the following: Hyperviscosity syndrome, cryoglobulinemia types 1 and 2, coagulation abnormalities, sensorimotor peripheral neuropathy, cold agglutinin disease and anemia, primary amyloidosis, tissue deposition of amorphous IgM in the skin, GI tract, kidneys, and other organs. Second, neoplastic lymphoplasmacytic cells infiltrate the bone marrow, spleen, and lymph nodes. Less commonly, these cells can infiltrate the liver, lungs, GI tract, kidneys, skin, eyes, and central nervous system (CNS). Infiltration of these organs causes numerous clinical symptoms and signs. Waldenstrm macroglobulinemia is an indolent disorder, and patients survive for a median of approximately 78 months. Different studies have been performed to assess prognosis. Patients with a nodular type of bone marrow involvement tend to do better than those with diffuse involvement. Bustoros et al identified the following as independent predictors of progression from asymptomatic to overt Waldenstrm macroglobulinemia: Immunoglobulin M 4500 mg/dL, bone marrow lymphoplasmacytic infiltration 70%, beta2-microglobulin 4.0 mg/dL, serum albumin 3.5 g/dL. The most important causes of death in Waldenstrm macroglobulinemia include progression of the proliferative process, infection, cardiac failure, renal failure, strokes, and GI bleeding. Transformation to a more aggressive immunoblastic variant is less common (6% of cases).

• #50 Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies

  https://www.mdpi.com/1422-0067/23/19/11145

  The presence of MYD88 L265P somatic mutation is present in 91% of WM/LPL patients, per whole genome sequencing results. The presence of MYD88 L265P has also been reported in IgM MGUS, mucosa-associated lymphoid tissue lymphoma (9%), and diffuse large B-cell lymphoma. […] Bing–Neel syndrome (BNS) is a rare complication of WM. Two types of BNS exist, diffuse and tumoral form. In diffuse form, malignant cells are found in the leptomeningeal space, periventricular white matter, or the spinal cord. The tumoral form is characterized by an intraparenchymal mass or nodular lesion. BNS is rare, with only 1% of patients showing BNS during the disease progression.

• #51 Waldenström’s Macroglobulinemia | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/waldenstroms-macroglobulinemia

  Waldenstrm’s macroglobulinemia (WM) is an uncommon blood cell cancer that originates from malignant B-cells. It is a slow-growing type of non-Hodgkin lymphoma. Waldenstrm’s mostly forms in the bone marrow and can slow normal blood cell growth, which can lead to anemia and a weakened immune system. […] Many patients do not have symptoms when they are diagnosed. For these individuals, WM may be discovered during routine blood or imaging tests. Symptomatic patients may have symptoms due to anemia (tiredness, weakness, dizziness, shortness of breath, headaches) or other deficiencies in blood counts due to the high number of WM cells in the bone marrow, enlarged lymph nodes, or spleen. They may also have symptoms due to the IgM protein made by the WM cells, including neuropathy (numbness, tingling, burning or pain) in the legs and feet or arms and hands; cryoglobulinemia (skin lesions or joint pain); cold agglutinemia (tiredness, weakness, dizziness, sweating, shortness of breath); and rarely, kidney, brain, or spinal cord involvement.

• #52 Waldenström Macroglobulinemia Symptoms May be Gastro-Related

  https://www.cancertherapyadvisor.com/news/waldenstrom-macroglobulinemia-symptoms/

  Gastrointestinal-tract involvement may be a comorbid condition in patients with Waldenstrm macroglobulinemia. […] Common symptoms typically include weakness, fatigue, and weight loss but GI involvement is generally considered to be rare. […] The patient described in the case report was a man aged 69 years with Waldenstrm macroglobulinemia who initially had chronic watery diarrhea for 6 months. […] The diarrhea returned 2 months later during budesonide treatment and was accompanied by weight loss. […] This case adds to the many different ways Waldenstrm macroglobulinemia can present involving the GI tract and points to the need for considering this diagnosis along with other common causes of chronic diarrhea and TI ulceration the study authors wrote. Our case also demonstrates that the GI symptoms of Waldenstrm macroglobulinemia respond well to therapy.

• #53 Waldenström’s Macroglobulinemia | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/waldenstroms-macroglobulinemia

  Waldenstrm’s may start with a very early condition, called a precursor condition. Precursors for WM are: Smoldering Waldenstrm’s Macroglobulinemia (SWM): In this precursor condition, there are high numbers of abnormal lymphocytes and plasma cells in the bone marrow that secrete M proteins of IgM type. Patients with SWM usually do not have symptoms. Monoclonal Gammopathy of Undetermined Significance (MGUS): Abnormal plasma cells are in the bone marrow but there is no cancer. The abnormal plasma cells produce monoclonal (M) proteins. In some patients, MGUS may later progress to a more serious condition or cancer, such as Waldenstrm’s or multiple myeloma.

• #54 Bing Center for Waldenstrom’s Macroglobulinemia – About Waldenstrom’s Macroglobulinemia

  http://waldenstroms.com/about-wm

  Waldenströms may start with a very early condition, called a precursor condition. Smoldering Waldenströms Macroglobulinemia (SWM): In this precursor condition, high concentrations of abnormal lymphocytes and plasma cells are found in the bone marrow and secrete M proteins of IgM type but patients are largely without symptoms. Monoclonal Gammopathy of Undetermined Significance (MGUS): Abnormal plasma cells are in the bone marrow – but there is no cancer. The abnormal plasma cells produce monoclonal (M) proteins. In most patients, the amount of M protein changes little over time, and there are no symptoms or problems. In some patients, MGUS may later become a more serious condition or cancer, such as Waldenströms.

• #55 Progression in smoldering Waldenström macroglobulinemia: long-term results

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3362362/

  Smoldering WM (SWM) is a poorly described asymptomatic disorder with a high risk of progressing to symptomatic WM requiring treatment. It is defined by the presence of serum IgM 3 g/dL and/or 10% bone marrow lymphoplasmacytic infiltration but no evidence of end-organ damage (eg, symptomatic anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly) that can be attributed to a plasma cell proliferative disorder. […] The cumulative probability of progression to symptomatic WM requiring therapy, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 68% at 10 years. […] The progression rate during the first 5 years was 92% for the 13 patients who had 50% or more lymphoplasmacytic cells in the bone marrow at diagnosis and 46% for those with bone marrow infiltration of less than 50% (P = .001).

• #56 Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies

  https://www.mdpi.com/1422-0067/23/19/11145

  Waldenströms macroglobulinemia is an indolent, B-cell lymphoma without a known cure. […] Approximately 75% of WM patients have symptoms at the time of diagnosis and anemia is common, as WM cell growth in the bone marrow progresses. Hyperviscosity syndrome, caused by abnormal IgM secretion and accumulation in the blood, occurs in 10–30% of patients and may be life-threatening. […] WM has an associated precursor disease, monoclonal gammopathy of undetermined significance (MGUS) of IgM type. IgM MGUS is defined by a serum concentration of 3 g/dL or less of IgM paraprotein, the absence of proliferation of plasma cells, and a population of 10% or less of bone marrow plasma cells. MGUS can progress to WM, and typically does so at a rate of 1% per year, indicating the importance of understanding IgM MGUS.

• #57 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  Patients at one end of the disease spectrum do not require treatment: those with IgM monoclonal gammopathy of unknown significance (MGUS) and those with smoldering Waldenstrms macroglobulinemia. […] Treatment is initiated when patients develop symptomatic Waldenstrms macroglobulinemia, which is defined as any-level serum IgM and 10% bone marrow involvement with the presence of end-organ damage related to the underlying IgM, he indicated. […] Although observation is usually appropriate for patients with IgM MGUS and smoldering Waldenstrms macroglobulinemia, Dr. Nooka described scenarios that warrant the initiation of treatment: History: Fever 101F, drenching night sweats, weight loss, severe neuropathy, severe fatigue. […] If these findings can be tied to the underlying disease process, thats a trigger for me to start treatment.

• #58 Progression in smoldering Waldenström macroglobulinemia: long-term results

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3362362/

  The purpose of this study was to define the risk of progression and survival of patients with smoldering Waldenstrm macroglobulinemia (SWM). SWM is defined clinically as having a serum monoclonal IgM protein 3 g/dL and/or 10% bone marrow lymphoplasmacytic infiltration but no evidence of end-organ damage (anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly). […] During 285 cumulative person-years of follow-up of the 48 patients with SWM (median, 15.4 years), 34 (71%) progressed to symptomatic Waldenstrm macroglobulinemia (WM) requiring treatment, one to primary amyloidosis, and one to lymphoma (total, 75%). The cumulative probability of progression to symptomatic WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 68% at 10 years.

• #59 Progression in smoldering Waldenström macroglobulinemia: long-term results

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3362362/

  Smoldering WM (SWM) is a poorly described asymptomatic disorder with a high risk of progressing to symptomatic WM requiring treatment. It is defined by the presence of serum IgM 3 g/dL and/or 10% bone marrow lymphoplasmacytic infiltration but no evidence of end-organ damage (eg, symptomatic anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly) that can be attributed to a plasma cell proliferative disorder. […] The cumulative probability of progression to symptomatic WM requiring therapy, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 68% at 10 years. […] The progression rate during the first 5 years was 92% for the 13 patients who had 50% or more lymphoplasmacytic cells in the bone marrow at diagnosis and 46% for those with bone marrow infiltration of less than 50% (P = .001).

• #60

  https://link.springer.com/article/10.1007/s44178-024-00083-y

  Early progression of disease within 24 months (POD24) after diagnosis has been recognized as an important prognostic factor in several indolent lymphomas such as follicular lymphoma. […] The median OS in patients with POD24 was 40 months (95%CI: 15.264.0), which was significantly shorter than that without POD24 (156 months, 95%CI: 123.6188.4; HR: 6.587, 95% CI 4.3929.881, P0.0001). […] Patients with a very high-risk rIPSSWM stage were more likely to have POD24 (P=0.020). […] Our study found that approximately 25% of patients experienced early progression within 24 months after induction treatment, which was consistent with previous reports. […] The prognostic impact of POD24 was still strong when adjusted to R-IPSSWM. […] Among patients experienced relapse or progression, early POD within 24 months also played a role in the prediction of the poor prognosis.

• #61 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  WM-related peripheral neuropathy is reported by 25% of newly diagnosed WM patients as their presenting symptom. […] Rarely (affecting 1% patients during the disease course), lymphoplasmacytic lymphoma (LPL) can infiltrate the central nervous system (Bing–Neel Syndrome), leading to clinical presentation with a spectrum of neurological symptoms, from headache/visual disturbance to seizures and cognitive decline to cranial neuropathies and sensory disturbance according to the localisation of disease. […] The median time for patients to progress to symptomatic disease is approximately five years and the main risk factors for progression are IgM paraprotein concentration, degree of bone marrow infiltration with lymphoplasmacytic cells and haemoglobin value.

• #62 Progression in smoldering Waldenström macroglobulinemia: long-term results

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3362362/

  The most important risk factors in our study for progression of SWM were the degree of lymphoplasmacytic infiltration of the bone marrow, hemoglobin value, and size of the IgM monoclonal protein. […] Progression of SWM is almost limited to the subsequent development of symptomatic WM, but an occasional patient may develop AL amyloidosis or lymphoma. […] The median survival after progression to symptomatic WM was 5.1 years.

• #63 Diagnostics in Waldenström’s macroglobulinemia: a consensus statement of the European Consortium for Waldenström’s Macroglobulinemia | Leukemia

  https://www.nature.com/articles/s41375-022-01762-3

  However, the cut-off point of 1.5g/dl could be misleading since in WM, there is no concordance between BM infiltration, IgM levels and patient symptoms. […] Consequently, although the value of BM assessment in asymptomatic individuals is not fully established, most groups currently agree that it may provide prognostic information about the risk of progression and the indication of the BM biopsy should be discussed. […] A progressive increase in the number of light-chain-isotype-positive B-cells from IgM-MGUS to smoldering and to symptomatic WM has been demonstrated. However, the pattern of antigen expression and the relative fractions of individual marker expressing clonal B-cells remain stable during disease progression. […] Deletion of 6q (6q or del6q) is the most frequent chromosomal abnormality (40-50% of patients) and it is directly related with progression from asymptomatic to symptomatic WM. […] Deletion of 17p/TP53 is present in 8-15% of WM patients, and TP53 mutations are present in a small subset of patients with poor prognosis.

• #64

  https://link.springer.com/article/10.1007/s44178-024-00083-y

  Early progression of disease within 24 months (POD24) after diagnosis has been recognized as an important prognostic factor in several indolent lymphomas such as follicular lymphoma. […] The median OS in patients with POD24 was 40 months (95%CI: 15.264.0), which was significantly shorter than that without POD24 (156 months, 95%CI: 123.6188.4; HR: 6.587, 95% CI 4.3929.881, P0.0001). […] Patients with a very high-risk rIPSSWM stage were more likely to have POD24 (P=0.020). […] Our study found that approximately 25% of patients experienced early progression within 24 months after induction treatment, which was consistent with previous reports. […] The prognostic impact of POD24 was still strong when adjusted to R-IPSSWM. […] Among patients experienced relapse or progression, early POD within 24 months also played a role in the prediction of the poor prognosis.

• #65

  https://link.springer.com/article/10.1007/s44178-024-00083-y

  The use of effective and novel agents after progression may improve the survival of POD24 patients in the traditional treatment group and this may partially explain the difference. […] In multivariable analysis, high advanced R-IPSSWM stage was useful in the identification of patients with POD24. […] Based on our study, patients with early POD had a worse outcome compared with those with late POD, which suggested that POD24 could be applied for the risk stratification of patients with relapse or progression.

• #66

  http://waocp.com/journal/index.php/apjcc/article/view/1173

  The symptoms are caused by neoplastic infiltration of organs and elevated levels of IgM paraprotein. Patients usually present with constitutional symptoms like fatigue, fever, weight loss. […] In the present study, 38% had constitutional symptoms, 50% had anaemia, 15% each had thrombocytopenia, lymphadenopathy, hepatosplenomegaly and symptoms of hyperviscosity. […] The diagnosis of WML is usually challenging. About 25% of patients are asymptomatic at diagnosis, with 40% to 70% developing symptomatic disease within 3 years and 10 years of diagnosis. […] Symptoms related to hyperviscosity include headache, visual disturbances, neurologic symptoms and bleeding. Precipitation of IgM paraproteins can result in cryoglobulinemia causing Raynaud phenomena and cold urticaria. […] The 3-year progression-free survival and overall survival rates were 69.4% and 78%, respectively.

• #67 New Advances in Waldenström Macroglobulinemia

  https://www.onclive.com/view/new-advances-in-waldenstr-m-macroglobulinemia

  Waldenstrm Macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by the malignant accumulation of IgM-producing lymphoplasmacytic cells in the bone marrow and other organs. The genomic profile impacts the clinical presentation of patients with WM. For example, patients with CXCR4-mutated disease typically present with high serum IgM levels, symptomatic hyperviscosity, and acquired von Willebrand disease. In contrast, patients with MYD88 wild-type disease have a higher risk of an aggressive transformation and experience inferior survival outcomes. […] One-third of patients are diagnosed with WM in an asymptomatic phase, also known as smoldering or inactive WM. These patients have an overall survival similar to age-, sex-, and race-matched individuals of the general population. The asymptomatic WM risk scoring system uses the percentage of bone marrow involvement, serum IgM, albumin, and beta-2-microglobulin levels to identify patients at high, intermediate, and low risk of needing therapy. As WM is currently incurable using standard therapies, and the available therapies can induce adverse effects, therapy should be reserved for patients with symptomatic WM whose activities of daily living are impacted by the disease. Approximately 80% of patients with asymptomatic WM will require therapy within 10 years of diagnosis. Criteria for treating WM include symptomatic anemia; constitutional symptoms such as fevers, drenching night sweats, or unintentional weight loss; symptomatic hyperviscosity; progressive neuropathy; and symptomatic lymphadenopathy or organomegaly.

• #68 Diagnosis and Risk Stratification in Waldenström Macroglobulinemia in: Journal of the National Comprehensive Cancer Network Volume 22 Issue 7 (2024)

  https://jnccn.org/abstract/journals/jnccn/22/7/article-e247024.xml

  Importantly, the serum viscosity level and the symptom complex, rather than the absolute serum IgM level, should be relied on for making a diagnosis of symptomatic hyperviscosity and consideration of urgent plasma exchange. Rapid hemolysis and anemia, with or without acrocyanosis from cold agglutinin disease, can rarely be a presenting feature in 1% to 2% of patients. […] Histologic transformation to an aggressive lymphoma is encountered in up to 4%, and typically occurs late in the disease course. […] Symptoms in such cases are driven by amyloid deposition related organ dysfunction. […] Complications such as histologic transformation or light and/or heavy chain (AL/ALH) amyloidosis are infrequent, their occurrence adversely influences the disease course.

• #69 Waldenström Macroglobulinemia: Possible Effects – The Waiting Room

  https://thewaitingroom.karger.com/tell-me-about/waldenstrom-macroglobulinemia-possible-effects/

  This can cause bouts of fatigue and breathlessness and may cause the urine to become very dark from time to time, especially when conditions are cooler. […] Tell your doctor if you experience breathlessness, dizziness when standing up, low blood pressure, new intolerance of blood pressure medication, diarrhea, weight loss or symptoms of peripheral neuropathy (such as numbness, tingling or pain in your hands or feet). […] In a small number of people, WM develops into an aggressive non-Hodgkin lymphoma in a process called high-grade transformation. Transformation means that LPL cells develop the biological characteristics of diffuse large B-cell lymphoma (DLBCL). This is usually accompanied by rapidly noticeable changes, such as new swellings, sweats and weight loss.

• #70 Waldenstrom Macroglobulinemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/207097-overview

  Waldenstrm macroglobulinemia, one of the malignant monoclonal gammopathies, is a chronic, indolent, lymphoproliferative disorder. It is characterized by the presence of a high level of a macroglobulin (immunoglobulin M [IgM]), elevated serum viscosity, and the presence of a lymphoplasmacytic infiltrate in the bone marrow. The clinical manifestations of Waldenstrm macroglobulinemia result from the presence of the IgM paraprotein and malignant lymphoplasmacytic cell infiltration of the bone marrow and other tissue sites. The clinical presentation is similar to that of multiple myeloma except that (1) organomegaly is common in Waldenstrm macroglobulinemia and is uncommon in multiple myeloma and (2) lytic bony disease and renal disease are uncommon in Waldenstrm macroglobulinemia but are common in multiple myeloma. Waldenstrm macroglobulinemia is not curable, but a number of therapies have shown activity in the disease. For asymptomatic patients without end-organ damage, management consists of careful observation. In symptomatic patients, monotherapy with rituximab is the usual choice, especially for nonbulky disease. Bulky symptomatic disease may require combination regimens, such as chemotherapy. Hyperviscosity syndrome may mandate emergency plasmapheresis. Complications of Waldenstrm macroglobulinemia include the following: Hyperviscosity syndrome, visual disturbances secondary to hyperviscosity syndrome, diarrhea and malabsorption secondary to gastrointestinal (GI) involvement, kidney disease (less common), amyloidosis of the heart, kidney, liver, lungs, and joints, bleeding manifestations secondary to platelet dysfunction and coagulation factor and fibrinogen abnormalities due to interaction with plasma IgM, peripheral neuropathy, Raynaud phenomenon secondary to cryoglobulinemia, increased predisposition to infection due to B-cell dysfunction (disease related) or T-cell dysfunction (therapy related, particularly after nucleoside analogues), cardiac failure, increased incidence of lymphomas, myelodysplasia, and leukemias. The clinical manifestations of this disorder result from 2 important factors. First, secretion of the IgM paraprotein leads to hyperviscosity and vascular complications because of physical, chemical, and immunologic properties of the paraprotein. These complications include the following: Hyperviscosity syndrome, cryoglobulinemia types 1 and 2, coagulation abnormalities, sensorimotor peripheral neuropathy, cold agglutinin disease and anemia, primary amyloidosis, tissue deposition of amorphous IgM in the skin, GI tract, kidneys, and other organs. Second, neoplastic lymphoplasmacytic cells infiltrate the bone marrow, spleen, and lymph nodes. Less commonly, these cells can infiltrate the liver, lungs, GI tract, kidneys, skin, eyes, and central nervous system (CNS). Infiltration of these organs causes numerous clinical symptoms and signs. Waldenstrm macroglobulinemia is an indolent disorder, and patients survive for a median of approximately 78 months. Different studies have been performed to assess prognosis. Patients with a nodular type of bone marrow involvement tend to do better than those with diffuse involvement. Bustoros et al identified the following as independent predictors of progression from asymptomatic to overt Waldenstrm macroglobulinemia: Immunoglobulin M 4500 mg/dL, bone marrow lymphoplasmacytic infiltration 70%, beta2-microglobulin 4.0 mg/dL, serum albumin 3.5 g/dL. The most important causes of death in Waldenstrm macroglobulinemia include progression of the proliferative process, infection, cardiac failure, renal failure, strokes, and GI bleeding. Transformation to a more aggressive immunoblastic variant is less common (6% of cases).

• #71 About Waldenström’s macroglobulinaemia (WM) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/lymphoma/non-hodgkin/types/waldenstroms-macroglobulinaemia

  Sometimes people develop numbness or tingling in their hands and feet. They may also have problems with their balance. This is due to nerve damage (neuropathy) caused by the abnormal protein in the blood. […] WM is a low-grade lymphoma and normally develops slowly. Rarely it can change (transform) to a high-grade lymphoma.

• #72 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  Everyones situation is different, particularly with a condition that progresses slowly like Waldenstrm macroglobulinemia. Research shows that 66% of people (more than 2 out of 3) are alive 10 years after theyre diagnosed. But life expectancy varies by age. Many people diagnosed over age 65 (the most commonly diagnosed age group) die from causes unrelated to WM. […] If you have questions about your situation, talk to your healthcare provider. They know you and the circumstances that may affect your health.

• #73 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  WM can cause a wide variety of signs and symptoms. The most common are slowly progressing fatigue and shortness of breath with exertion due to anemia. The anemia is the result of the decrease in red blood cells caused by the increased number of lymphoplasmacytic (LPL) cells in the bone marrow. Other typical signs and symptoms are abnormal bleeding from gums and nose, dizziness, decreased red blood cell count, neurological symptoms such as peripheral neuropathy, enlarged lymph nodes, enlarged spleen, weight loss, and night sweats. Most symptoms are attributable to a decrease in red blood cells caused by the proliferation of the lymphoplasmacytic (LPL) cells of WM or to the secretion of monoclonal IgM (hyperviscosity, peripheral neuropathy and autoimmune hemolytic anemia). […] Although WM is incurable, in most cases it can be effectively treated to provide a good quality of life for many years. In most people, WM is a slow growing (indolent), chronic disease. The median survival after diagnosis has varied in studies, from 5-10 years in the past to 15-20 years now. Another way to answer this question is to look at the five-year survival rate, which indicates what percentage of people live at least five years after cancer is found. The current five-year survival rate for people with WM is about 78%. In other words, nearly four out of five people live for at least five years after being diagnosed with WM. However, it is important to note that survival rates vary based on individual factors, including the person’s age and whether there are other medical problems. It is also important to remember that statistics on the survival rates for people with WM are an estimate. As newer, safer, and more effective drugs become available, the life expectancy will continue to increase. The main causes of death because of WM include disease progression, transformation to an aggressive lymphoma, or complications from therapy. What is most important is that the time frame for living with WM has increased dramatically and is continuing to increase, and people with WM will likely die from something unrelated to WM.

• #74 How long will I live with WM? – HealthTree for Waldenström’s Macroglobulinemia

  https://healthtree.org/waldenstroms-macroglobulinemia/community/how-long-will-i-live-with-waldenstr%C3%B6m’s-macroglobulinemia

  Waldenstrm’s Macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma that affects the white blood cells. […] The prognosis and life expectancy for someone with WM can vary greatly depending on a number of factors. […] According to the American Cancer Society, the overall 5-year survival rate for people with WM is about 78%, and the 10-year survival rate is about 64%. […] Many people with WM live much longer than these statistics suggest. […] It’s also worth noting that because WM is slow-growing and often diagnosed in older adults, some people may die from other causes before the WM becomes life-threatening. […] Patients who have symptoms at diagnosis tend to have a worse prognosis.

• #75 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  WM can cause a wide variety of signs and symptoms. The most common are slowly progressing fatigue and shortness of breath with exertion due to anemia. The anemia is the result of the decrease in red blood cells caused by the increased number of lymphoplasmacytic (LPL) cells in the bone marrow. Other typical signs and symptoms are abnormal bleeding from gums and nose, dizziness, decreased red blood cell count, neurological symptoms such as peripheral neuropathy, enlarged lymph nodes, enlarged spleen, weight loss, and night sweats. Most symptoms are attributable to a decrease in red blood cells caused by the proliferation of the lymphoplasmacytic (LPL) cells of WM or to the secretion of monoclonal IgM (hyperviscosity, peripheral neuropathy and autoimmune hemolytic anemia). […] Although WM is incurable, in most cases it can be effectively treated to provide a good quality of life for many years. In most people, WM is a slow growing (indolent), chronic disease. The median survival after diagnosis has varied in studies, from 5-10 years in the past to 15-20 years now. Another way to answer this question is to look at the five-year survival rate, which indicates what percentage of people live at least five years after cancer is found. The current five-year survival rate for people with WM is about 78%. In other words, nearly four out of five people live for at least five years after being diagnosed with WM. However, it is important to note that survival rates vary based on individual factors, including the person’s age and whether there are other medical problems. It is also important to remember that statistics on the survival rates for people with WM are an estimate. As newer, safer, and more effective drugs become available, the life expectancy will continue to increase. The main causes of death because of WM include disease progression, transformation to an aggressive lymphoma, or complications from therapy. What is most important is that the time frame for living with WM has increased dramatically and is continuing to increase, and people with WM will likely die from something unrelated to WM.

• #76

  http://waocp.com/journal/index.php/apjcc/article/view/1173

  The 3-year OS was 78 %. OS for patients with age group 65 years was 75 with a P value of 0.47. There was no significant difference in OS with respect to age, sex, B symptoms, hemoglobin level, platelet count, serum LDH, monoclonal protein level in SPE, beta2 microglobulin. […] The median survival of patients with WM is about 7.4 years, mortality is associated with symptomatic disease, whereas asymptomatic patients have survival similar to the general population.

• #77 Lymphoplasmacytic Lymphoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513356/

  Most Waldenstrom macroglobulinemia patients have monoclonal IgM. A minority can have both IgM and IgG. Waldenstrom macroglobulinemia patients can present with hyperviscosity symptoms (30%), autoimmune hemolysis (20%), coagulopathy, and/or diarrhea. Symptoms related to hyperviscosity include visual impairment, neurologic symptoms (neuropathy), bleeding, new-onset headaches, blurred vision, and cryoglobulinemia leading to Raynaud phenomena and cold urticaria. The neuropathy is sensory and affects more the feet than hands in a bilaterally symmetric pattern. The autoimmune hemolysis is due to cold agglutinins (IgM antibodies that bind at less than 37 C). […] The median survival of lymphoplasmacytic lymphoma patients is approximately five years. About 40% of patients survive for ten years or more. Typically, the cause of death is more due to advance age-associated comorbidities than WM.

• #78 Frequently Asked Questions – Waldenstrom’s Macroglobulinemia – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

  WM can cause a wide variety of signs and symptoms. The most common are slowly progressing fatigue and shortness of breath with exertion due to anemia. The anemia is the result of the decrease in red blood cells caused by the increased number of lymphoplasmacytic (LPL) cells in the bone marrow. Other typical signs and symptoms are abnormal bleeding from gums and nose, dizziness, decreased red blood cell count, neurological symptoms such as peripheral neuropathy, enlarged lymph nodes, enlarged spleen, weight loss, and night sweats. Most symptoms are attributable to a decrease in red blood cells caused by the proliferation of the lymphoplasmacytic (LPL) cells of WM or to the secretion of monoclonal IgM (hyperviscosity, peripheral neuropathy and autoimmune hemolytic anemia). […] Although WM is incurable, in most cases it can be effectively treated to provide a good quality of life for many years. In most people, WM is a slow growing (indolent), chronic disease. The median survival after diagnosis has varied in studies, from 5-10 years in the past to 15-20 years now. Another way to answer this question is to look at the five-year survival rate, which indicates what percentage of people live at least five years after cancer is found. The current five-year survival rate for people with WM is about 78%. In other words, nearly four out of five people live for at least five years after being diagnosed with WM. However, it is important to note that survival rates vary based on individual factors, including the person’s age and whether there are other medical problems. It is also important to remember that statistics on the survival rates for people with WM are an estimate. As newer, safer, and more effective drugs become available, the life expectancy will continue to increase. The main causes of death because of WM include disease progression, transformation to an aggressive lymphoma, or complications from therapy. What is most important is that the time frame for living with WM has increased dramatically and is continuing to increase, and people with WM will likely die from something unrelated to WM.

• #79 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  Patients at one end of the disease spectrum do not require treatment: those with IgM monoclonal gammopathy of unknown significance (MGUS) and those with smoldering Waldenstrms macroglobulinemia. […] Treatment is initiated when patients develop symptomatic Waldenstrms macroglobulinemia, which is defined as any-level serum IgM and 10% bone marrow involvement with the presence of end-organ damage related to the underlying IgM, he indicated. […] Although observation is usually appropriate for patients with IgM MGUS and smoldering Waldenstrms macroglobulinemia, Dr. Nooka described scenarios that warrant the initiation of treatment: History: Fever 101F, drenching night sweats, weight loss, severe neuropathy, severe fatigue. […] If these findings can be tied to the underlying disease process, thats a trigger for me to start treatment.

• #80 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  In severe cases, WM can cause complications, including: Amyloidosis. This condition happens when faulty proteins build up in organs like your heart, lungs and kidneys. Cryoglobulinemia. This condition happens when certain blood proteins that react to cold conditions gather in clumps in your hands and feet. This can cause pain and turn your hands and feet blue or white (cyanosis). […] As there isnt a cure for this condition, the best treatment is one that relieves symptoms with the least amount of side effects. […] Your healthcare provider will work with you to customize treatment. Options for WM include: Watchful waiting. Your provider may not start treatment if you dont have symptoms. Some people with WM dont need treatment for years. Plasmapheresis (plasma exchange). Providers use a machine to filter abnormal IgM from your plasma, the liquid part of your blood. They return the plasma to your bloodstream. Providers use this treatment to ease symptoms caused by thickening blood. Immunotherapy. This treatment uses your bodys immune system to destroy or slow the growth of WM cells. Providers commonly prescribe rituximab (Rituxan) alone or with chemotherapy.

• #81 New Advances in Waldenström Macroglobulinemia

  https://www.onclive.com/view/new-advances-in-waldenstr-m-macroglobulinemia

  Waldenstrm Macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by the malignant accumulation of IgM-producing lymphoplasmacytic cells in the bone marrow and other organs. The genomic profile impacts the clinical presentation of patients with WM. For example, patients with CXCR4-mutated disease typically present with high serum IgM levels, symptomatic hyperviscosity, and acquired von Willebrand disease. In contrast, patients with MYD88 wild-type disease have a higher risk of an aggressive transformation and experience inferior survival outcomes. […] One-third of patients are diagnosed with WM in an asymptomatic phase, also known as smoldering or inactive WM. These patients have an overall survival similar to age-, sex-, and race-matched individuals of the general population. The asymptomatic WM risk scoring system uses the percentage of bone marrow involvement, serum IgM, albumin, and beta-2-microglobulin levels to identify patients at high, intermediate, and low risk of needing therapy. As WM is currently incurable using standard therapies, and the available therapies can induce adverse effects, therapy should be reserved for patients with symptomatic WM whose activities of daily living are impacted by the disease. Approximately 80% of patients with asymptomatic WM will require therapy within 10 years of diagnosis. Criteria for treating WM include symptomatic anemia; constitutional symptoms such as fevers, drenching night sweats, or unintentional weight loss; symptomatic hyperviscosity; progressive neuropathy; and symptomatic lymphadenopathy or organomegaly.

• #82 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  Patients at one end of the disease spectrum do not require treatment: those with IgM monoclonal gammopathy of unknown significance (MGUS) and those with smoldering Waldenstrms macroglobulinemia. […] Treatment is initiated when patients develop symptomatic Waldenstrms macroglobulinemia, which is defined as any-level serum IgM and 10% bone marrow involvement with the presence of end-organ damage related to the underlying IgM, he indicated. […] Although observation is usually appropriate for patients with IgM MGUS and smoldering Waldenstrms macroglobulinemia, Dr. Nooka described scenarios that warrant the initiation of treatment: History: Fever 101F, drenching night sweats, weight loss, severe neuropathy, severe fatigue. […] If these findings can be tied to the underlying disease process, thats a trigger for me to start treatment.

• #83 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  Patients can be observed carefully with periodic measurement of the M component, immunoglobulin, and serum viscosity. […] Clinical indications for initiation of therapy include the following: Recurrent fever, night sweats, weight loss, fatigue. […] Macroglobulinemia can cause complications similar to peripheral neuropathy; cryoglobulinemia or amyloidosis can occur in the absence of high IgM concentrations and manifestations of the lymphomatous process. These symptoms largely result from certain physicochemical properties of the monoclonal IgM protein and can be treated by repeated plasmapheresis followed by systemic therapy. However, evidence supporting plasma exchange for the treatment of peripheral neuropathy associated with IgM paraprotein is weak (grade of recommendation C).

• #84 When Waldenstrom’s macroglobulinaemia comes back – WMUK

  https://www.wmuk.org.uk/your-journey-with-wm/when-waldenstroms-macroglobulinaemia-comes-back/

  The aim of having treatment is to reduce the amount of cells that cause Waldenstroms macroglobulinaemia in your body, to help get rid of WM symptoms and make you feel better. […] When treatment finishes, most people go into what is called remission. This is where their blood tests show no, or reduced amounts, of the abnormal IgM protein, and their symptoms are reduced or have gone away. […] This period of remission can last for months, years or even decades, because Waldenstroms macroglobulinaemia is a slow-growing cancer and it takes the cells time to rebuild to the levels that cause symptoms. […] At these check-ups, you might be told that the cells causing WM have grown to a point that your healthcare team can see that it is getting worse, for example the levels of abnormal IgM are increasing. This is called relapse. The news may come as a surprise, although many people feel their WM symptoms coming back and might already feel unwell.

• #85 When Waldenstrom’s macroglobulinaemia comes back – WMUK

  https://www.wmuk.org.uk/your-journey-with-wm/when-waldenstroms-macroglobulinaemia-comes-back/

  Sometimes, your healthcare team might see the signs of relapse or progression in your blood results before you start to feel unwell. […] If you think your symptoms are returning, or have developed new symptoms, you should speak to your healthcare team as this might be a sign your Waldenstroms macroglobulinaemia has relapsed.

• #86 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  In severe cases, WM can cause complications, including: Amyloidosis. This condition happens when faulty proteins build up in organs like your heart, lungs and kidneys. Cryoglobulinemia. This condition happens when certain blood proteins that react to cold conditions gather in clumps in your hands and feet. This can cause pain and turn your hands and feet blue or white (cyanosis). […] As there isnt a cure for this condition, the best treatment is one that relieves symptoms with the least amount of side effects. […] Your healthcare provider will work with you to customize treatment. Options for WM include: Watchful waiting. Your provider may not start treatment if you dont have symptoms. Some people with WM dont need treatment for years. Plasmapheresis (plasma exchange). Providers use a machine to filter abnormal IgM from your plasma, the liquid part of your blood. They return the plasma to your bloodstream. Providers use this treatment to ease symptoms caused by thickening blood. Immunotherapy. This treatment uses your bodys immune system to destroy or slow the growth of WM cells. Providers commonly prescribe rituximab (Rituxan) alone or with chemotherapy.

• #87 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  The activity of these regimens is not affected by mutation status, but they are associated with certain treatment-related side effects; therefore, treatment should be individualized. […] The proteasome-containing regimens have yielded comparable outcomes in clinical trials, with response rates of around 70% and median progression-free survival of more than 40 months. […] Ibrutinib proved to be a game changer in Waldenstrms macroglobulinemia, having yielded an overall response rate of 90% and a major response rate of 73% in the pivotal trial. […] The mutation status helps us understand which patients should be treated with a BTK inhibitor, vs fixed-duration chemotherapy, where the outcome is not affected by mutation status, Dr. Nooka explained. […] The use of pirtobrutinib resulted in a major response rate of 67% in patients previously treated with a BTK inhibitor; at 18 months, 57% of these patients were progression-free, and 82% were alive.

• #88 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  The BCL2 inhibitor venetoclax may represent an additional option in this setting. […] Autologous stem cell transplantation remains an option for good-performance patients, especially those with limited treatment exposure who remain chemosensitive. […] In May 2020, the U.S. Food and Drug Administration granted CLR 131 Fast Track designation for patients with relapsed or refractory Waldenstrms macroglobulinemia or lymphoplasmacytic lymphoma.

• #89 New Advances in Waldenström Macroglobulinemia

  https://www.onclive.com/view/new-advances-in-waldenstr-m-macroglobulinemia

  Several treatment options exist for patients with symptomatic WM, but no large, randomized studies have compared the commonly used regimens. Therefore, treatment selection is highly personalized and should consider the patients clinical presentation, comorbidities, concurrent medications, genomic profile, treatment objective, and personal preferences. The modified staging system for WM is an externally validated multi-institutional prognostic model to estimate the survival of patients with active, symptomatic WM and uses age, serum beta-2-microglobulin, lactate dehydrogenase, and albumin to classify patients into low-, low-intermediate, intermediate, and high-risk disease. […] Beyond deep and durable responses, advantages of chemoimmunotherapy include a fixed duration, potentially allowing patients to be off therapy for years. However, chemoimmunotherapy can induce cytopenias, a higher risk of infections, and the development of myeloid neoplasms. Over the past decade, Bruton tyrosine kinase (BTK) inhibitors have become a standard treatment option. Ibrutinib was highly effective in WM and induced deep and durable responses. The combination of ibrutinib (Imbruvica) and rituximab induced deeper and more durable responses than rituximab plus placebo in the phase 3 INNOVATE study. Zanubrutinib was as effective as ibrutinib but was associated with lower rates of diarrhea, rash, and atrial fibrillation in the phase 3 ASPEN study.

• #90 New Advances in Waldenström Macroglobulinemia

  https://www.onclive.com/view/new-advances-in-waldenstr-m-macroglobulinemia

  The advantages of BTK inhibitors include the ease of oral administration and the absence of risk of myeloid neoplasms. On the other hand, BTK inhibitors are associated with unique adverse events, such as an increased risk of bleeding, hypertension, and arrhythmia. The duration of therapy is indefinite and should continue until disease progression or unacceptable toxicity.

• #91 Get Waldenstrom Macroglobulinemia Treatment | Cleveland Clinic

  https://my.clevelandclinic.org/services/waldenstrom-macroglobulinemia-treatment

  Especially if you havent had symptoms. This is often the case with slow-growing Waldenstrom macroglobulinemia (WM) also called lymphoplasmacytic lymphoma. […] When you notice symptoms, its a sign that the cancer has progressed, and youll likely need treatment. […] You may not have any symptoms but signs of WM may show up in tests for another health condition. Or you may notice gradual signs of this condition, like night sweats, fatigue, loss of appetite, shortness of breath, blurred vision, nosebleeds, fever and swollen lymph nodes. […] All of this can cause anemia, increased infections (with low white blood cells, a condition called neutropenia), bleeding and bruising (thrombocytopenia). It also can cause more serious complications like amyloidosis or cyroglobulinemia. […] There are different ways to treat Waldenstrom macroglobulinemia symptoms. You may have only one treatment or a combination of them, like: […] If you need treatment, youll likely be offered one or more options that attack or replace cancer cells in your blood. These treatments can ease or get rid of symptoms for months, or even years.

• #92 When Waldenstrom’s macroglobulinaemia comes back – WMUK

  https://www.wmuk.org.uk/your-journey-with-wm/when-waldenstroms-macroglobulinaemia-comes-back/

  The aim of having treatment is to reduce the amount of cells that cause Waldenstroms macroglobulinaemia in your body, to help get rid of WM symptoms and make you feel better. […] When treatment finishes, most people go into what is called remission. This is where their blood tests show no, or reduced amounts, of the abnormal IgM protein, and their symptoms are reduced or have gone away. […] This period of remission can last for months, years or even decades, because Waldenstroms macroglobulinaemia is a slow-growing cancer and it takes the cells time to rebuild to the levels that cause symptoms. […] At these check-ups, you might be told that the cells causing WM have grown to a point that your healthcare team can see that it is getting worse, for example the levels of abnormal IgM are increasing. This is called relapse. The news may come as a surprise, although many people feel their WM symptoms coming back and might already feel unwell.

• #93 When Waldenstrom’s macroglobulinaemia comes back – WMUK

  https://www.wmuk.org.uk/your-journey-with-wm/when-waldenstroms-macroglobulinaemia-comes-back/

  Sometimes, your healthcare team might see the signs of relapse or progression in your blood results before you start to feel unwell. […] If you think your symptoms are returning, or have developed new symptoms, you should speak to your healthcare team as this might be a sign your Waldenstroms macroglobulinaemia has relapsed.

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