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Multiple Myeloma

Plasma-Cell Myeloma

Multiple myeloma is a neoplastic disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow.

Multiple Myeloma - Symptom Checker

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Presentation

Easy Bruising
  • When they do occur, symptoms include: Bone pain, particularly in the back and ribs Easily broken bones (fractures) Tiredness, lethargy or shortness of breath on exertion – usually caused by too few red blood cells in the body (anaemia) Easy bruising or[betterhealth.vic.gov.au]
  • bruising Amyloidosis can be determined from any of the problems listed above.[unckidneycenter.org]
  • Easy bruising or bleeding. Trouble breathing. Weakness of the arms or legs. Feeling very tired. A tumor can damage the bone and cause hypercalcemia (too much calcium in the blood).[my.clevelandclinic.org]
Dyspnea
  • Cardiopulmonary symptoms such as shortness of breath, exertional dyspnea, orthopnea, and dependent edema should raise concern for secondary AL amyloidosis or light chain deposition disease with cardiac involvement.[cancertherapyadvisor.com]
  • The dyspnea had progressed to the point that she could only walk one block without stopping.[archbronconeumol.org]
  • In patients at risk for cardiac AL (eg, an MGUS patient with new unexplained dyspnea on exertion, unrevealing ECHO results, and “clean coronaries” on an angiogram), cardiac biomarker screening is indicated, although a definitive diagnosis requires tissue[hematologyandoncology.net]
  • Diagnostic accuracy of emergency Doppler echocardiography for identification of acute left ventricular heart failure in patients with acute dyspnea: comparison with Boston criteria and N-terminal prohormone brain natriuretic peptide.[aou-careggi.toscana.it]
Hepatosplenomegaly
  • The presenting problem was proteinuria in five patients, thyromegaly in three patients, and hepatosplenomegaly in one patient.[jamanetwork.com]
  • On evaluation of the abdomen, hepatosplenomegaly may be discovered. Cardiovascular system examination may reveal cardiomegaly secondary to immunoglobulin deposition. Amyloidosis may develop in some patients with MM.[emedicine.medscape.com]
Visual Hallucination
  • hallucinations often accompany occipital ICH Coma at presentation has been reported in a small proportion of patients (0.4-19%) with ICH.[emedicine.medscape.com]
Polyuria
  • Hypercalcemia may cause polyuria and polydipsia, muscle cramps, constipation, and a change in the patient’s mental status. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, et al.[emedicine.medscape.com]
Confusion
  • She became acutely confused with a Glasgow Coma Scale score of 10/15 and a CT head showed no acute pathology. Further investigation with a lumbar puncture confirmed the diagnosis of streptococcal meningitis.[ncbi.nlm.nih.gov]
  • When signs and symptoms do occur, they can include: Bone pain, especially in your spine or chest Nausea Constipation Loss of appetite Mental fogginess or confusion Fatigue Frequent infections Weight loss Weakness or numbness in your legs Excessive thirst[mayoclinic.org]
  • Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures[cancer.uvahealth.com]
  • People often have bone pain and fractures, and they may also have kidney problems, a weakened immune system (immunocompromise), weakness, and confusion.[merckmanuals.com]
  • Large amounts of calcium can enter the bloodstream, causing confusion, pain and kidney failure.[nm.org]
Peripheral Neuropathy
  • ., thalidomide or bortezomib, has also been associated with the occurrence of a serious and common adverse effect, drug-induced peripheral neuropathy. The mechanism of the development of the peripheral neuropathy is poorly understood.[ncbi.nlm.nih.gov]
  • Although gastrointestinal disturbances and fatigue are the most common adverse effects, peripheral neuropathy and thrombocytopenia are the key dose-limiting toxicities of bortezomib-based combination regimens.[ncbi.nlm.nih.gov]
  • The pooled RRs for rate of adverse events (AEs), such as thrombocytopenia and bortezomib-induced peripheral neuropathy (BIPN), were 0.79 (95% CI: 0.68-0.92) and 0.63 (95% CI: 0.51-0.79), respectively.[ncbi.nlm.nih.gov]
  • Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade 3 PNP between 2%-23% Schlafer et al., 2017.[ncbi.nlm.nih.gov]
  • Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a[ncbi.nlm.nih.gov]
Stroke
  • This stops the blood clogging small blood vessels, which can cause confusion, dizziness and stroke-like symptoms.[betterhealth.vic.gov.au]
  • Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt[emedicine.medscape.com]
  • ., headache, blurred vision, tinnitus, delirium, stroke], respiratory compromise) Not recognizing very early signs of infection (tachycardia, delirium). Not protecting the kidneys. Not recognizing progression of disease.[clinicaladvisor.com]
  • Research Focus Molecular epidemiology Genetic susceptibility Hematopoietic malignancies Gynecologic tumors Stroke and related cardiovascular endpoints Childhood cancers and conditions Immune biomarkers Infectious and viral causes of cancer There are a[cityofhope.org]
  • Other symptoms can include stroke , gastrointestinal disorders, enlarged liver , diminished spleen function , diminished function of the adrenal and other endocrine glands, skin color change or growths, lung problems, bleeding and bruising problems ,[en.wikipedia.org]
Headache
  • Herein, we describe an extraordinary rare case of multiple myeloma with initial presentation of a left sphenoid neoplasm resulting in left-sided headache and rapid deterioration of visual acuity.[ncbi.nlm.nih.gov]
  • Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures[cancer.uvahealth.com]
  • ., headache, blurred vision, tinnitus, delirium, stroke], respiratory compromise) Not recognizing very early signs of infection (tachycardia, delirium). Not protecting the kidneys. Not recognizing progression of disease.[clinicaladvisor.com]
  • In some cases, an increase in the thickness ( viscosity ) of the blood may lead to headaches or problems with vision.[labtestsonline.org]
Dizziness
  • One patient experienced dose limiting toxicity of dizziness and diarrhea. The most frequent non-hematologic toxicity was infection (79%). Serious adverse events included cord compression and sepsis.[ncbi.nlm.nih.gov]
  • This stops the blood clogging small blood vessels, which can cause confusion, dizziness and stroke-like symptoms.[betterhealth.vic.gov.au]
  • Common signs and symptoms/complications of multiple myeloma include : Anemia - A person with a low red blood cell count (anemia) will exhibit symptoms such as fatigue, weakness, shortness of breath and dizziness due to inadequate oxygenation to tissues[cancersupportcommunity.org]
  • Amyloid deposits can also cause irregular heartbeats (arrhythmia) which can cause breathlessness, dizziness or fainting Neuropathy: amyloid deposits affecting your nerves.[myeloma.org.uk]
Pain
  • Patients with very good partial response (VGPR) or better reported reduced scores for pain severity and worst pain; those with progressive disease reported increased scores for these domains and pain interference.[ncbi.nlm.nih.gov]
  • She was admitted with a complaint of low back pain. Regarding the presence of back pain, anemia, hypercalcemia, and kidney failure, a diagnosis of MM was suspected. A skeletal survey showed punched-out lesions in the skull.[ncbi.nlm.nih.gov]
  • His abdominal pain became localized in the infraumbilical area and a small mass was palpated on the right lower quadrant on subsequent examination.[ncbi.nlm.nih.gov]
  • A 36 year old male presented to the emergency department with severe epigastric pain, nausea, vomiting without hematemesis, diarrhea and anorexia. He presented with respiratory distress, shock and fever at the emergency.[ncbi.nlm.nih.gov]
  • We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury.[ncbi.nlm.nih.gov]
Anemia
  • The patient in our case study suffered refractory anemia following surgery and 2 cycles of chemotherapy. Initially, the anemia was considered to be a common manifestation of CRC in this patient.[ncbi.nlm.nih.gov]
  • Multiple myeloma most commonly affects patients who are 60 years of age, and causes clinical symptoms from anemia, lytic bone lesions, hypercalcemia, and renal failure.[ncbi.nlm.nih.gov]
  • Here, we report one MM case complicated by Evans syndrome (Autoimmun hemolytic anemia (AIHA) associated with thrombocytopenia).[ncbi.nlm.nih.gov]
  • This interferes with blood cell production leading to anemia, leukopenia, and thrombocytopenia. High levels of infection are common which can lead to the overproduction of certain antibodies.[symptoma.com]
  • Here we report a patient with MM presenting with renal failure, anemia, and bone pain. The renal biopsy showed DDD. The patient received anti-myeloma treatment and responded well. The case is discussed and literature reviewed.
.[ncbi.nlm.nih.gov]
Fatigue
  • She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ.[ncbi.nlm.nih.gov]
  • The primary objective is to investigate the prognostic value of patient self-reported fatigue severity for overall survival.[ncbi.nlm.nih.gov]
  • In the bone marrow, myeloma cells crowd out healthy white blood cells and red blood cells, leading to fatigue and an inability to fight infections.[mayoclinic.org]
  • Although gastrointestinal disturbances and fatigue are the most common adverse effects, peripheral neuropathy and thrombocytopenia are the key dose-limiting toxicities of bortezomib-based combination regimens.[ncbi.nlm.nih.gov]
  • […] combination with bortezomib or lenalidomide plus dexamethasone resulted in longer PFS (HR 0.83, 95% CI: 0.66-0.98), fewer incidences of at least grade 3 thrombocytopenia (RR 0.35, 95% CI: 0.23-0.53), neutropenia (RR 0.70, 95% CI: 0.51-0.96), and sense of fatigue[ncbi.nlm.nih.gov]
Weakness
  • We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury.[ncbi.nlm.nih.gov]
  • These events lead to bone pain, kidney damage, and a weak immune system.[cancer.uvahealth.com]
  • Bones in the spine may get weak and even collapse. They can press on certain nerves, causing severe pain, numbness, and/or muscle weakness. Abnormal proteins made by myeloma cells can damage nerves, causing weakness and numbness.[cancersupportcommunity.org]
  • Multiple Myeloma Bone Bone pain Fractures in bones Weakness Fatigue Weight loss Repeated infections Nausea Vomiting Constipation Problems with urination Weakness or numbness in legs Back pain Rib pain Age: 35 years and older Gender: men Race: African-American[nm.org]
  • Patients with anemia may experience fatigue, weakness, and shortness of breath with exercise. In advanced cases, patients typically have recurrent infections and can have kidney failure.[orthoinfo.aaos.org]
Fever
  • A 64-year-old Japanese man with multiple myeloma was admitted to our institute due to fever and hypotension. He had received multiple courses of chemotherapy just before his febrile episode. Blood culturing detected Morganella morganii.[ncbi.nlm.nih.gov]
  • He presented with respiratory distress, shock and fever at the emergency.[ncbi.nlm.nih.gov]
  • Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints. The coexistence of multiple myeloma (MM) and FMF is an extremely rare event.[ncbi.nlm.nih.gov]
  • A 68-year-old female from Florida (USA) with low-risk lambda light chain multiple myeloma complicated by persistently low CD4 counts, absolute neutrophil counts and IgG levels presented 18 months after diagnosis with fever, pneumonia, new-onset atrial[ncbi.nlm.nih.gov]
  • Though her condition was under control in some degree, she discontinued treatment due to significant side effects such as fatigue, hyperhidrosis, fever, chill, larynx mucosa ulcers, pharynx mucosa ulcers, and poor appetite.[ncbi.nlm.nih.gov]
Nausea
  • She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ.[ncbi.nlm.nih.gov]
  • A 36 year old male presented to the emergency department with severe epigastric pain, nausea, vomiting without hematemesis, diarrhea and anorexia. He presented with respiratory distress, shock and fever at the emergency.[ncbi.nlm.nih.gov]
  • When signs and symptoms do occur, they can include: Bone pain, especially in your spine or chest Nausea Constipation Loss of appetite Mental fogginess or confusion Fatigue Frequent infections Weight loss Weakness or numbness in your legs Excessive thirst[mayoclinic.org]
  • Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures[cancer.uvahealth.com]
  • Multiple Myeloma Bone Bone pain Fractures in bones Weakness Fatigue Weight loss Repeated infections Nausea Vomiting Constipation Problems with urination Weakness or numbness in legs Back pain Rib pain Age: 35 years and older Gender: men Race: African-American[nm.org]
Constipation
  • The patient got severe constipation with difficulty in the passage of both gas and feces for 7 days. The patient was diagnosed with a small intestinal obstruction initially and then developed type II respiratory failure.[ncbi.nlm.nih.gov]
  • An 87-year-old Hispanic man with a past medical history of hypertension, diabetes, and constipation, presented to an emergency department complaining of severe generalized abdominal pain and profuse diarrhea for 3 days.[ncbi.nlm.nih.gov]
  • When signs and symptoms do occur, they can include: Bone pain, especially in your spine or chest Nausea Constipation Loss of appetite Mental fogginess or confusion Fatigue Frequent infections Weight loss Weakness or numbness in your legs Excessive thirst[mayoclinic.org]
  • Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures[cancer.uvahealth.com]
  • Multiple Myeloma Bone Bone pain Fractures in bones Weakness Fatigue Weight loss Repeated infections Nausea Vomiting Constipation Problems with urination Weakness or numbness in legs Back pain Rib pain Age: 35 years and older Gender: men Race: African-American[nm.org]
Diarrhea
  • For this reason we report this rare case in which diarrhea and abdominal pain were the initial presenting symptoms of multiple myeloma with a plasmacytoma.[ncbi.nlm.nih.gov]
  • A 36 year old male presented to the emergency department with severe epigastric pain, nausea, vomiting without hematemesis, diarrhea and anorexia. He presented with respiratory distress, shock and fever at the emergency.[ncbi.nlm.nih.gov]
  • One patient experienced dose limiting toxicity of dizziness and diarrhea. The most frequent non-hematologic toxicity was infection (79%). Serious adverse events included cord compression and sepsis.[ncbi.nlm.nih.gov]
  • Side effects can depend on which drugs were given and how much, but include fatigue, hair loss, poor appetite, nausea or vomiting, diarrhea, or infertility.[hopkinsmedicine.org]
  • For example, gastrointestinal dysfunction may require treatment for symptoms that include poor nutritional health, diarrhea or constipation, and nausea or vomiting.[amyloidosis.org]
Polydipsia
  • Hypercalcemia may cause polyuria and polydipsia, muscle cramps, constipation, and a change in the patient’s mental status. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, et al.[emedicine.medscape.com]
Bleeding Gums
  • gums and heavy periods Myeloma doesn't usually cause a lump or tumour.[nhs.uk]
  • However, if you have these symptoms, you should call your doctor right away: Fever Bleeding (such as nosebleeds, bleeding gums or severe bruising) Skin rash Cough that doesn’t go away These are some of the more serious side effects of melphalan.[familydoctor.org]
Cardiomegaly
  • Cardiovascular system examination may reveal cardiomegaly secondary to immunoglobulin deposition. Amyloidosis may develop in some patients with MM.[emedicine.medscape.com]
Retinal Hemorrhage
  • Sludging in the capillaries resulting in purpura, papilledema, central nervous system symptoms, retinal hemorrhage, or coronary ischemia can occur.[symptoma.com]
  • Purpura, retinal hemorrhage, papilledema, coronary ischemia, seizures, and confusion may occur as a result of hyperviscosity syndrome.[emedicine.medscape.com]
Cotton Wool Spots
  • Physical Examination On head, ears, eyes, nose, and throat (HEENT) examination, the eyes may show exudative macular detachment, retinal hemorrhage, or cotton-wool spots. Pallor from anemia may be present.[emedicine.medscape.com]
Purpura
  • Two patients (33.3%) experienced AE (also considered adverse drug reactions) leading to study discontinuation: thrombotic microangiopathy (Day 11/Cycle 1) and thrombotic thrombocytopenic purpura (Day 6/Cycle 2).[ncbi.nlm.nih.gov]
  • Post-proctoscopic peripalpebral purpura strongly suggests amyloidosis.[emedicine.medscape.com]
  • Sludging in the capillaries resulting in purpura, papilledema, central nervous system symptoms, retinal hemorrhage, or coronary ischemia can occur.[symptoma.com]
  • Blood diseases involving destruction by the body's own immune system of platelets are also treated with dexamethasone, disease like idiopathic thrombocytopenia purpura, and red blood cells (autoimmune hemolytic anemia.[medicinenet.com]
  • Clinical manifestations with head and neck purpura, unexplained submandibular swelling, signs of heart diastolic dysfunction such as jugular venous distention (white arrowhead), or stiff indented macroglossia, although found in no more than 15% of patients[bloodjournal.org]
Pruritus
  • Her pruritus resolved, but the lesions persisted. Footnotes Competing interests: None declared. This article has been peer reviewed.[cmaj.ca]
Bone Pain
  • Here we report a patient with MM presenting with renal failure, anemia, and bone pain. The renal biopsy showed DDD. The patient received anti-myeloma treatment and responded well. The case is discussed and literature reviewed.
.[ncbi.nlm.nih.gov]
  • The clinical features are bone pain, renal impairment, immunodeficiency, anemia and presence of abnormal immunoglobulins (Ig).[orpha.net]
  • A few months later, the patient presented with acute Kidney Injury, bone pain, and anemia. A diagnosis of MM was made based on the bone marrow biopsy. Treatment of MM decreased proteinuria and improved renal function.[ncbi.nlm.nih.gov]
  • Multiple myeloma can also affect your bones, leading to bone pain, thinning bones and broken bones. Reduced kidney function. Multiple myeloma may cause problems with kidney function, including kidney failure.[mayoclinic.org]
  • Treatment of relapsed/refractory multiple myeloma (RRMM) aims to prolong survival while maintaining health-related quality of life (HRQoL) by managing disease-related symptoms and complications-one of the most frequent and debilitating being bone pain[ncbi.nlm.nih.gov]
Back Pain
  • She was admitted with a complaint of low back pain. Regarding the presence of back pain, anemia, hypercalcemia, and kidney failure, a diagnosis of MM was suspected. A skeletal survey showed punched-out lesions in the skull.[ncbi.nlm.nih.gov]
  • The typical presentation of multiple myeloma is anemia, back pain, and an elevated sedimentation rate. Patients with multiple myeloma have hypercalcemia but it's rarely manifested as acute pancreatitis.[ncbi.nlm.nih.gov]
  • Multiple Myeloma Bone Bone pain Fractures in bones Weakness Fatigue Weight loss Repeated infections Nausea Vomiting Constipation Problems with urination Weakness or numbness in legs Back pain Rib pain Age: 35 years and older Gender: men Race: African-American[nm.org]
  • Symptomatic myeloma is associated with hypercalcemia, renal insufficiency, anemia, and bone disease manifested as bony pain (classically back pain) or atraumatic fractures.[clinicaladvisor.com]
  • If the patient is presenting symptoms of weakness, back pain, numbness, or dysesthesias in their extremities a spinal cord compression should be considered. Severe cases of anemia can be present.[symptoma.com]
Myopathy
  • Neurologic findings may include a sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy, a Tinel sign, or a Phalen sign due to carpel tunnel compression secondary to amyloid deposition[emedicine.medscape.com]
  • Anno: 1998 - ISBN: Titolo Myopathy as the persistently isolated symptomatology of primary autoimmune hypothyroidism.[polime.it]
  • Gastro-intestinal tract Direct biopsy verification with symptoms Lung Direct biopsy verification with symptoms Interstitial radiographic pattern Soft tissues Tongue enlargement, arthropathy, claudication (presumed vascular amyloid), skin lesions, myopathy[ojrd.biomedcentral.com]
  • Gertz MA, Kyle RA: Myopathy in primary systemic amyloidosis. J Neurol Neurosurg Psychiatry 1996;60:655-660. Jardinet D, Westhovens R, Peeters J: Sicca syndrome as an initial symptom of amyloidosis. Clin Rheumatol 1998;17:546-548.[karger.com]
Low Back Pain
  • She was admitted with a complaint of low back pain. Regarding the presence of back pain, anemia, hypercalcemia, and kidney failure, a diagnosis of MM was suspected. A skeletal survey showed punched-out lesions in the skull.[ncbi.nlm.nih.gov]
Phalen's Sign
  • Neurologic findings may include a sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy, a Tinel sign, or a Phalen sign due to carpel tunnel compression secondary to amyloid deposition[emedicine.medscape.com]
Epistaxis
  • Patients with a high tumor volume may present with epistaxis. Generalized malaise, fever, sluggish mentation, paresthesia, sensory loss, and infection can indicate hyperviscosity.[symptoma.com]
  • Not recognizing Tumor Lysis Syndrome (although rare, this can result in significant morbidity) Not recognizing Hyperviscocity Syndrome (may present as bleeding, particularly epistaxis, neurologic complaints [i.e., headache, blurred vision, tinnitus, delirium[clinicaladvisor.com]
  • Epistaxis may be a presenting symptom of MM with a high tumor volume.[emedicine.medscape.com]

Workup

The standard workup for patients who are suspected of having multiple myeloma includes many components. The 2009 International Workshop created guidelines to standardize the investigative workup:

  • Bone marrow biopsy and/or bone marrow aspiration
  • Skeletal survey
  • Standard metaphase cytogenetics
  • MRI’s
  • Fluorescent in situ hybridization
  • Urine and serum assessment for monoclonal protein
  • Serum-free light chain assay
  • Serum beta (2)-microglobulin, lactate dehydrogenase, and albumin measurement
  • Complete blood count looking for thrombocytopenia, anemia, leukopenia
  • A complete metabolic panel of protein, albumin and globulin, creatinine, uric acid, and blood urea nitrogen levels.
  • A 24-hour urine collection to quantify creatinine and Bence Jones protein clearance

Imaging

PET scans and whole body MRI’s can be used to evaluate the extent of the multiple myeloma. Using both scanning techniques is thought to be helpful in assessing the effectiveness of expensive and aggressive treatments. Currently, however, PET scans are not part of standard practices. Bone scans should not be used in evaluating multiple myeloma as more than 50% of lesions tend to be missed.

Others

Bone marrow biopsies and aspirations can be used to evaluate the extent of malignancy. Using both allows the doctor to calculate the percentage of plasma cells in the aspirate, though the biopsy tends to be more accurate.

Staging

There are currently two staging systems in use to determine the severity of multiple myeloma in patients. The Salmon-Durie System has been in use since 1975 and the International Staging System was developed in 2005 [4] [5] [6].

Salmon-Durie Staging System

Stage 1:

  • Cell mass is less than 0.6 × 1012 cells/m2
  • Serum calcium value less than 12 mg/dL
  • Hemoglobin value greater than 10 g/dL
  • Only one bone plasmatoma on radiographs or a normal bone structure with a scale of 0
  • Urine light-chain M component on electrophoresis less than 4 g/24 h
  • IgG value less than 5 g/dL
  • IgA value less than 3 g/dL

Stage 2:

  • Cell mass is 0.6-1.2 × 1012 cells/m2
  • Does not meet the criteria for stage 1 or stage 3

Stage 3:

  • Cell mass is greater than 1.2 × 1012 cells/m2
  • Serum calcium value greater than 12 mg/dL
  • Advanced lytic bone lesions (scale 3) on radiographs
  • Hemoglobin value equal to 8.5 g/dL
  • IgG value greater than 7 g/dL
  • IgA value greater than 5 g/dL
  • Urine light-chain M component on electrophoresis greater than 12 g/24 h

International Staging System

Stage 1:

  • CRP ≥4.0 mg/dL
  • Beta-2 microglobulin less than or equal to 3.5 g/dL and albumin ≥3.5 g/dL
  • Absence of chromosome 13 deletion
  • Low serum IL-6 receptor
  • Plasma cell labeling index < 1%
  • Long duration of initial plateau phase

Stage 2:

  • Beta-2 microglobulin level ≥3.5 to < 5.5 g/dL, or
  • Beta-2 microglobulin < 3.5 g/dL and albumin < 3.5 g/dL

Stage 3:

  • Beta-2 microglobulin of 5.5 g/dL or more
Hyperviscosity
  • General processes Hyperviscosity syndrome can occur with immunoglobulin A, immunoglobulin G3, and immunoglobulin G1.[symptoma.com]
  • Hyperviscosity: Emergent plasmapheresis B.[clinicaladvisor.com]
  • Hyperviscosity is managed through plasmapheresis and prompt initiation of chemotherapy targeting the MM-clone.[cancertherapyadvisor.com]
  • Hyperviscosity Hyperviscosity may be associated with a number of symptoms, including generalized malaise, infection, fever, paresthesia, sluggish mentation, and sensory loss.[emedicine.medscape.com]
  • Hyperviscosity syndrome results from the increased presence of serum immunoglobulin proteins or blood cells causing an abnormal "thickness" to the blood.[labtestsonline.org]
Hyponatremia
  • Anno: 2006 - ISBN: Titolo What is the pathogenesis of hyponatremia after subarachnoid hemorrhage? Autori Benvenga S. Abstract Anno pubblicazione e riferimenti Nat Clin Pract Endocrinol Metab. 2006 Nov;2(11):608-9.[polime.it]
Elevated Sedimentation Rate
  • The typical presentation of multiple myeloma is anemia, back pain, and an elevated sedimentation rate. Patients with multiple myeloma have hypercalcemia but it's rarely manifested as acute pancreatitis.[ncbi.nlm.nih.gov]
Creatinine Increased
  • The blood urea increased to 8.1 mmol/L (normal 7.1 mmol/L) and creatinine increased to 158 μmol/L (normal 133 μmol/L). Then, a bone marrow biopsy was performed, showing 26% pleomorphic plasma cells (normal 15%).[ncbi.nlm.nih.gov]
Urea Increased
  • The blood urea increased to 8.1 mmol/L (normal 7.1 mmol/L) and creatinine increased to 158 μmol/L (normal 133 μmol/L). Then, a bone marrow biopsy was performed, showing 26% pleomorphic plasma cells (normal 15%).[ncbi.nlm.nih.gov]

Treatment

The main options for therapy include:

  • Chemotherapy and immunosuppression (melphalan, cyclophosphamide, doxorubicin, thalidomide, lenalidomide, bortezomib, carfilzomib, pomalidomide, prednisone and dexamethasone)
  • Autologous stem cell transplantation
  • Radiation
  • Surgical care

Prognosis

Prognosis of multiple myeloma is determined by 2 factors - how many tumors there are and how fast they are spreading. C-reactive protein and beta-2 microglobulin are both used to predict survival.

The median survival rates are as follows:

  • 54 months if both proteins are less than 6 mg/L
  • 27 months when only one protein is less than 6 mg/L
  • 6 months when both proteins are more than 6mg/L

Factors that led to a poor prognosis are hypercalcemia, renal impairment, tumor mass, and Bence Jones proteinemia. Patients that undergo conventional therapy have an average survival rate of 3 years. Fifty percent of patients who undergo high-dose chemotherapy with stem-cell transplantation survive for longer than 5 years [3]. The leading cause of death for patients with a myeloma is a bacterial infection.

Etiology

To date an exact cause for multiple myeloma has not been identified, but various factors have been suggested [1] [2]. Since most individuals diagnosed with the disorder are in the older age group the common thought is that decreased immune system that comes with age increases the chance of developing multiple myeloma. While no evidence suggests that the disease is hereditary, it has been reported in 2 or more first degree relatives and in identical twins. Oncogenes such as c-myc have been associated with plasma cell tumors early in their development.

Individuals working with toxic chemicals such as insecticides, herbicides, heavy metals, petroleum products, and asbestos could be at an increased risk for developing multiple myeloma though the risk cannot be quantified. A correlation between multiple myeloma and radiation has been identified in examining the medical histories of Nagasaki WWII survivors, who were exposed to more than 50 Gy of radiation. Of the 109,000 survivors, 29 died of a multiple myeloma between 1950 and 1976. While a link between pre-existing inflammatory diseases and multiple myeloma has been suggested, no case-control studies have been able to support the relationship.

Epidemiology

Annually, approximately 4 in 100,000 people are diagnosed with multiple myeloma. The condition is twice as common in African Americans, followed by Caucasians and half as common with Asian Americans. The predominant age of diagnosis is between 40 and 80 years old. The median age of diagnosis for men is 69 and for women is 71. Men are one and a half times more likely to be diagnosed with multiple myeloma than women. The malignancy is one of African American’s top 10 causes of cancer deaths.

Sex distribution
Age distribution

Pathophysiology

Multiple myeloma is characterized by the rapid growth of abnormal plasma cells in more than 10% of the patient’s bone marrow. Research suggests that the bone marrow microenvironment impacts the manner in which myelomas develop tumor cells. The cells that most often become malignant in multiple myelomas are the most mature of the B-lymphocytes. This occurs when the DNA sequence is rearranged when encoding into the structure of mature immunoglobulins. During the encoding immunoglobulin A, monoclonal immunoglobulin G, and/or light chains are overproduced. This overproduction is identified through the use of urine protein electrophoresis, or serum protein electrophoresis. Multiple myelomas are often the consequence of injuries or diseases in hematologic, renal, skeletal, and nervous systems as well as general processes.

General processes

Hyperviscosity syndrome can occur with immunoglobulin A, immunoglobulin G3, and immunoglobulin G1. Sludging in the capillaries resulting in purpura, papilledema, central nervous system symptoms, retinal hemorrhage, or coronary ischemia can occur.

Hematologic processes

Neutropenia, thrombocytopenia, and anemia result from plasma cells infiltrating bone marrow which can impact clotting factors leading to defects in how it interacts with other systems.

Renal processes

Renal processes linked to multiple myeloma, are most commonly amyloidosis, direct tubular injury, or mechanisms involved in plasmacytoma. Diagnoses of hyperuricemia, hypercalcemic nephropathy, glomerulosclerosis, and light-chain nephropathy are also possible.

Skeletal processes

Wide spread skeletal destruction is caused by a rapid increase in plasma cells. Skeletal destruction is accompanied with anemia, hypercalcemia, and osteolytic lesions. When the bone is destroyed, it is replaced by tumors which can lead to spinal cord compression, pathologic fracture, and pain. A compression fracture of the vertebral body can occur.

Neurologic processes

Skeletal destruction and nerve compression can cause spinal cord compression and/or radiculopathy.

Prevention

There are no guidelines for prevention of multiple myeloma.

Summary

Multiple myeloma, also known as plasma cell myeloma, myeloma, myelomatosis, and Kahler’s disease, is part of an incapacitating spectrum of malignancies including monoclonal gammopathy of unknown significance (MGUS) and plasma cell leukemia. Typically a multiple myeloma involves the skeleton and bone marrow with malignant proliferation of plasma cells. This interferes with blood cell production leading to anemia, leukopenia, and thrombocytopenia. High levels of infection are common which can lead to the overproduction of certain antibodies. This causes amyloidosis, hyperviscosity, and renal failure. There are life extending treatments, but currently no cure.

Patient Information

Multiple myeloma is a cancer of certain blood cells - plasma cells and it occurs in both the skeletal system and bone marrow. If you have been diagnosed with multiple myeloma then you could be experiencing any of the following symptoms: anemia, bleeding, bone pain, hypercalcemia, infection (often pneumococcal), kidney failure, malaise, neuropathies, pathologic fractures, spinal cord compression, or weakness.

There are no known causes of multiple myeloma; however, certain individuals have an increased risk of developing it. You have an increased risk of developing the condition if you are over 65, male, African American, have a family member who has been affected, or have either Monoclonal Gammopathy of Uncertain Significance (MGUS) or plasmacytoma.

If you have multiple myeloma you will through what is called induction therapy. The first stage involves chemotherapy to destroy the cancer (this will typically destroy many healthy cells too). Once you have gone through a round of chemotherapy, and if you are under the age of 70 you may have some stem cells removed and frozen through a process known as autologous stem cell transplantation. Those stem cells will be used later to lengthen your survival. Some people will receive two rounds of stem cell transplantation 6 months apart. Some patients might also do a round of radiation therapy which involves shooting a beam of radiation directly at the affected area.

Multiple myeloma treatments can cause you to feel nauseous or experience decreased immunity. Biophosphate therapy increases your risk of osteonecrosis of the jaw (exposure of the jaw bone through lesions).

References

Article

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  2. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet. Jul 25 2009;374(9686):324-39.
  3. Ludwig H, Durie BG, Bolejack V, Turesson I, Kyle RA, Blade J, et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood. Apr 15 2008;111(8):4039-47.
  4. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. May 5 2011;117(18):4701-5.
  5. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. Sep 1975;36(3):842-54.
  6. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. May 20 2005;23(15):3412-20.

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Last updated: 2018-06-22 08:02