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Topic: A comprehensive study of biochemistry of myeloma cells
Objectives: After the study following objectives can be full filled
Definition of myeloma cells Signs and symptoms Brief review of Diagnosis Pathophysiology An analysis of different available Treatments Prognosis
A detailed account of biochemistry of myeloma cells Comparative account of myeloma and normal cells
Research Method and Resources
This part of thesis envisages data collection from different sources of
information media, Google scholar, internet, various journals, magazines, and
many libraries.
Research is completely review based and coordination between different
aspects is made.
A group of doctors and medical students are also interviewed for the purpose.
In overall an Idea to generate awareness for early treatment and best available
treatments for a specific one are listed, so that both general reader and scholars
get benefited from the information compiled.
Multiple myeloma
http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myeloma7/27/2019 Proposal Chemistry
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From Wikipedia, the free encyclopedia
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Multiple myeloma
Classification and external resources
Micrograph of a plasmacytoma, the histologic correlate
of multiple myeloma. H&E stain
ICD-10 C90.0
ICD-9 203.0
ICD-O: M9732/3
OMIM 254500
DiseasesDB 8628
MedlinePlus 000583
eMedicine med/1521
MeSH D009101
Multiple myeloma (from Greekmyelo-, bone marrow), also known as plasma cell myeloma or
Kahler's disease (afterOtto Kahler), is a cancerofplasma cells, a type ofwhite blood cell
normally responsible for producing antibodies.[1]
In multiple myeloma, collections of abnormal
plasma cells accumulate in thebone marrow, where they interfere with the production of normalblood cells. Most cases of myeloma also feature the production of aparaproteinan abnormal
antibody which can cause kidney problems. Bone lesions and hypercalcemia (high calcium
levels) are also often encountered.[1]
http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/H%26E_stainhttp://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problemshttp://en.wikipedia.org/wiki/ICD-10http://en.wikipedia.org/wiki/ICD-10_Chapter_Chttp://apps.who.int/classifications/icd10/browse/2010/enhttp://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problemshttp://en.wikipedia.org/wiki/List_of_ICD-9_codeshttp://www.icd9data.com/getICD9Code.ashx?icd9=203.0http://en.wikipedia.org/wiki/International_Classification_of_Diseases_for_Oncologyhttp://en.wikipedia.org/wiki/ICD-Ohttp://www.progenetix.net/progenetix/I97323/http://en.wikipedia.org/wiki/OMIMhttp://omim.org/entry/254500http://en.wikipedia.org/wiki/Diseases_Databasehttp://www.diseasesdatabase.com/ddb8628.htmhttp://en.wikipedia.org/wiki/MedlinePlushttp://www.nlm.nih.gov/medlineplus/ency/article/000583.htmhttp://en.wikipedia.org/wiki/EMedicinehttp://www.emedicine.com/med/topic1521.htmhttp://en.wikipedia.org/wiki/Medical_Subject_Headingshttp://www.nlm.nih.gov/cgi/mesh/2013/MB_cgi?field=uid&term=D009101http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Hypercalcemiahttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Paraproteinhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/Plasma_cellhttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Otto_Kahlerhttp://www.nlm.nih.gov/cgi/mesh/2013/MB_cgi?field=uid&term=D009101http://en.wikipedia.org/wiki/Medical_Subject_Headingshttp://www.emedicine.com/med/topic1521.htmhttp://en.wikipedia.org/wiki/EMedicinehttp://www.nlm.nih.gov/medlineplus/ency/article/000583.htmhttp://en.wikipedia.org/wiki/MedlinePlushttp://www.diseasesdatabase.com/ddb8628.htmhttp://en.wikipedia.org/wiki/Diseases_Databasehttp://omim.org/entry/254500http://en.wikipedia.org/wiki/OMIMhttp://www.progenetix.net/progenetix/I97323/http://en.wikipedia.org/wiki/ICD-Ohttp://en.wikipedia.org/wiki/International_Classification_of_Diseases_for_Oncologyhttp://www.icd9data.com/getICD9Code.ashx?icd9=203.0http://en.wikipedia.org/wiki/List_of_ICD-9_codeshttp://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problemshttp://apps.who.int/classifications/icd10/browse/2010/enhttp://en.wikipedia.org/wiki/ICD-10_Chapter_Chttp://en.wikipedia.org/wiki/ICD-10http://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problemshttp://en.wikipedia.org/wiki/H%26E_stainhttp://en.wikipedia.org/wiki/Histologyhttp://en.wikipedia.org/wiki/Plasmacytomahttp://en.wikipedia.org/wiki/Micrographhttp://en.wikipedia.org/wiki/File:Plasmacytoma_ultramini1.jpghttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myeloma7/27/2019 Proposal Chemistry
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Myeloma is diagnosed withblood tests (serumprotein electrophoresis, serum free kappa/lambda
light chain assay),bone marrow examination, urine protein electrophoresis, and X-rays of
commonly involved bones. Myeloma is generally thought to be incurable but highly treatable.Remissions may be induced with steroids, chemotherapy, proteasome inhibitors (e.g.
bortezomib), immunomodulatory drugs (IMiDs) such as thalidomide orlenalidomide, and stem
cell transplants.Radiation therapyis sometimes used to reduce pain from bone lesions.
[1]
Myeloma develops in 14 per 100,000 people per year. It is more common in men, and for
unknown reasons is twice as common in African-Americans as it is in European-Americans.With conventional treatment, median survival is 34 years, which may be extended to 57 years
or longer with advanced treatments. Multiple myeloma is the second most common
hematological malignancy in the U.S. (afternon-Hodgkin lymphoma), and constitutes 1% of allcancers.
[1]
Contents
1 Signs and symptomso 1.1 Bone paino 1.2 Infectiono 1.3 Renal failureo 1.4 Anemiao 1.5 Neurological symptoms
2 Diagnosiso 2.1 Investigationso 2.2 Workupo 2.3 Diagnostic criteriao 2.4 Staging
3 Pathophysiology
4 Treatmento 4.1 Initial therapyo 4.2 Maintenance therapyo 4.3 Relapse
5 Prognosiso 5.1 Genetic testing
6 Epidemiology 7 Other animals 8 See also 9 References 10 External links
Signs and symptoms
Because many organs can be affected by myeloma, the symptoms and signs vary greatly. A
mnemonic sometimes used to remember the common tetrad (four parts) of multiple myeloma is
CRAB: C = Calcium (elevated), R = Renal failure, A = Anemia, B = Bone lesions.[2]
Myeloma
http://en.wikipedia.org/wiki/Stem_cell_transplanthttp://en.wikipedia.org/wiki/Stem_cell_transplanthttp://en.wikipedia.org/wiki/Stem_cell_transplanthttp://en.wikipedia.org/wiki/Radiation_therapyhttp://en.wikipedia.org/wiki/Radiation_therapyhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Mnemonichttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Non-Hodgkin_lymphomahttp://en.wikipedia.org/wiki/Hematological_malignancyhttp://en.wikipedia.org/wiki/White_Americanhttp://en.wikipedia.org/wiki/African-Americanhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Radiation_therapyhttp://en.wikipedia.org/wiki/Stem_cell_transplanthttp://en.wikipedia.org/wiki/Stem_cell_transplanthttp://en.wikipedia.org/wiki/Stem_cell_transplanthttp://en.wikipedia.org/wiki/Lenalidomidehttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Bortezomibhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Glucocorticoidhttp://en.wikipedia.org/wiki/Bone_marrow_examinationhttp://en.wikipedia.org/wiki/Protein_electrophoresishttp://en.wikipedia.org/wiki/Blood_test7/27/2019 Proposal Chemistry
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has many possible symptoms, an
here in decreasing order ofincid
Bone pain
Illustration showing the most com
Bone pain affects almost 70% o
pain usually involves the spine a
indicate a pathologicalbone fraccompression. Myeloma bone dis
Nuclear Factor B Ligand (RA
which resorb bone. The resultantseen in plain radiographs, which
"pepper pot" appearance of the s
release ofcalcium into the blood
Infection
The most common infections arepathogens include S. pneumonia
causingpyelonephritis includeE
period for the occurrence of infechemotherapy.
[4]The increased r
immunoglobulin level is typicall
are ineffective monoclonal antib
d all symptoms may be due to other causes. Th
nce.
on site of bone lesions in vertebrae. Seefull anima
patients and is the most common symptom.[3]
d ribs, and worsens with activity. Persistent lo
ure. Involvement of the vertebrae may lead to sease is due to the overexpression of Receptor A
KL) by bone marrow stroma. RANKL activate
bone lesions are lytic (cause breakdown) in natmay show "punched-out" resorptive lesions (in
ull on radiography). The breakdown of bone al
, leading to hypercalcemiaand its associated sy
pneumonias andpyelonephritis. Common pne, S. aureus, andK. pneumoniae, while commo
. coli and othergram-negative organisms. The g
tion is in the initial few months after the start oisk of infection is due to immune deficiency. Al
elevated in multiple myeloma, the majority o
dies from the clonal plasma cell. A selected gr
y are presented
tion.
yeloma bone
alized pain may
pinal cordctivator for
s osteoclasts,
ure and are bestluding the
so leads to
ptoms.
moniapathogens
reatest risk
fthough the total
the antibodies
up of patients
http://en.wikipedia.org/wiki/Incidence_%28epidemiology%29http://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Incidence_%28epidemiology%29http://blausen.com/index-wiki.php?word=Multiple+Myelomahttp://blausen.com/index-wiki.php?word=Multiple+Myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Hypercalcemiahttp://en.wikipedia.org/wiki/Hypercalcemiahttp://blausen.com/index-wiki.php?word=Multiple+Myelomahttp://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Gram-negativehttp://en.wikipedia.org/wiki/Escherichia_colihttp://en.wikipedia.org/wiki/Pyelonephritishttp://en.wikipedia.org/wiki/Klebsiella_pneumoniaehttp://en.wikipedia.org/wiki/Staphylococcus_aureushttp://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Pathogenhttp://en.wikipedia.org/wiki/Pyelonephritishttp://en.wikipedia.org/wiki/Pneumoniahttp://en.wikipedia.org/wiki/Hypercalcemiahttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Skullhttp://en.wikipedia.org/wiki/Osteoclasthttp://en.wikipedia.org/wiki/RANKLhttp://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Bone_fracturehttp://en.wikipedia.org/wiki/Multiple_myelomahttp://blausen.com/index-wiki.php?word=Multiple+Myelomahttp://en.wikipedia.org/wiki/File:Blausen_0656_MultipleMyeloma.pnghttp://en.wikipedia.org/wiki/File:Blausen_0656_MultipleMyeloma.pnghttp://en.wikipedia.org/wiki/Incidence_%28epidemiology%297/27/2019 Proposal Chemistry
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with documented hypogammagl
therapy to reduce the risk of infe
Renal failure
Renal failure may develop both
The most common cause of rena
the light chains. Increased bonethereby contributing to the renal
Light chains produce myriad eff
tubular acidosis).
Other causes include hyperurice
oftumorcells.
Anemia
The anemia found in myeloma is
replacement of normal bone marblood cell production (hematopo
Neurological symptoms
Common problems are weaknes
changes and retinopathy may be
properties of theparaprotein. Ficontrol (due to involvement ofs
syndromeand otherneuropathiegive rise toparaplegia in late pre
Diagnosis
Investigations
Serum protein electrophoresis sho
multiple myeloma.
bulinemia may benefit from replacement imm
ction.[5]
cutelyand chronically.
failure in Multiple Myeloma is due to tubulop
esorption leads to hypercalcemia and causes nefailure. Amyloidosis is a distant third in the cau
cts which can manifest as the Fanconi syndro
ia, recurrent infections (pyelonephritis), and l
usually normocytic and normochromic. It resul
ow by infiltrating tumor cells and inhibition ofiesis) by cytokines.
, confusion and fatigue due to hypercalcemia.
the result ofhyperviscosity of the blood depen
ally, there may be radicular pain, loss ofbowelinal cord leading to cord compression) orcarpa
(due to infiltration ofperipheral nerves by amsenting cases.
ing a paraprotein (peak in the gamma zone) in a p
noglobulin
thic effects of
hrocalcinosissation.
e (type II renal
cal infiltration
ts from the
normal red
eadache, visual
ing on the
or bladderl tunnel
loid). It may
tient with
http://en.wikipedia.org/wiki/Renal_failurehttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Hematopoiesishttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Paraplegiahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Acute_renal_failurehttp://en.wikipedia.org/wiki/Acute_renal_failurehttp://en.wikipedia.org/wiki/Chronic_renal_failurehttp://en.wikipedia.org/wiki/Hematopoiesishttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Protein_electrophoresishttp://en.wikipedia.org/wiki/File:Monoclonal_gammopathy_Multiple_Myeloma.pnghttp://en.wikipedia.org/wiki/File:Monoclonal_gammopathy_Multiple_Myeloma.pnghttp://en.wikipedia.org/wiki/Paraplegiahttp://en.wikipedia.org/wiki/Amyloidhttp://en.wikipedia.org/wiki/Peripheral_nerveshttp://en.wikipedia.org/wiki/Neuropathieshttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Carpal_tunnel_syndromehttp://en.wikipedia.org/wiki/Spinal_cord_compressionhttp://en.wikipedia.org/wiki/Spinal_cordhttp://en.wikipedia.org/wiki/Bowelhttp://en.wikipedia.org/wiki/Radicular_painhttp://en.wikipedia.org/wiki/Paraproteinhttp://en.wikipedia.org/wiki/Hyperviscosityhttp://en.wikipedia.org/wiki/Retinopathyhttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Hypercalcemiahttp://en.wikipedia.org/wiki/Fatigue_%28medical%29http://en.wikipedia.org/wiki/Confusionhttp://en.wikipedia.org/wiki/Weaknesshttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Hematopoiesishttp://en.wikipedia.org/wiki/Normochromichttp://en.wikipedia.org/wiki/Normocytichttp://en.wikipedia.org/wiki/Anemiahttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Pyelonephritishttp://en.wikipedia.org/wiki/Hyperuricemiahttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Renal_tubular_acidosishttp://en.wikipedia.org/wiki/Fanconi_syndromehttp://en.wikipedia.org/wiki/Chronic_renal_failurehttp://en.wikipedia.org/wiki/Acute_renal_failurehttp://en.wikipedia.org/wiki/Renal_failurehttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Hypogammaglobulinemia7/27/2019 Proposal Chemistry
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The presence of unexplained anemia, kidney dysfunction, a high erythrocyte sedimentation rate(ESR), lytic bone lesions, elevatedbeta-2 microglobulin, and/or a high serumprotein (especially
raised globulins orimmunoglobulin) may prompt further testing. The globulin level may benormal in established disease. A doctor will requestprotein electrophoresis of the blood and
urine, which might show the presence of aparaprotein (monoclonal protein, or M protein) band,
with or without reduction of the other (normal) immunoglobulins (known as immune paresis).One type of paraprotein is the Bence Jones protein which is a urinary paraprotein composed of
free light chains (see below). Quantitative measurements of the paraprotein are necessary to
establish a diagnosis and to monitor the disease. The paraprotein is an abnormal immunoglobulinproduced by the tumor clone. Very rarely, the myeloma is nonsecretory (not producing
immunoglobulins).
In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins
are most common, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition,
light and orheavy chains (the building blocks ofantibodies) may be secreted in isolation: - or-light chains or any of the five types of heavy chains (-, -, -, - or -heavy chains).
Additional findings include: a raised calcium (when osteoclasts are breaking down bone,releasing calcium into the bloodstream), raised serum creatinine due to reduced renal function,
which is mainly due to casts of paraprotein deposition in the kidney, although the cast may also
contain complete immunoglobulins, Tamm-Horsfall protein and albumin.[6]
Bone marrow aspirate showing the histologic correlate of multiple myeloma under the
microscope. H&E stain.
Plasmacytoma. H&E stain.
http://en.wikipedia.org/wiki/Tamm-Horsfall_proteinhttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/H%26E_stainhttp://en.wikipedia.org/wiki/H%26E_stainhttp://en.wikipedia.org/wiki/File:Cast_nephropathy_-_2_cropped_-_very_high_mag.jpghttp://en.wikipedia.org/wiki/File:Plasmacytoma1.jpghttp://en.wikipedia.org/wiki/H%26E_stainhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/File:Multiple_myeloma_(2)_HE_stain.jpghttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Tamm-Horsfall_proteinhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Renal_functionhttp://en.wikipedia.org/wiki/Creatininehttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Osteoclastshttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Antibodieshttp://en.wikipedia.org/wiki/Immunoglobulin_heavy_chainhttp://en.wikipedia.org/wiki/Immunoglobulin_light_chainhttp://en.wikipedia.org/wiki/IgEhttp://en.wikipedia.org/wiki/IgDhttp://en.wikipedia.org/wiki/IgMhttp://en.wikipedia.org/wiki/IgAhttp://en.wikipedia.org/wiki/IgGhttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Bence_Jones_proteinhttp://en.wikipedia.org/wiki/Paraproteinhttp://en.wikipedia.org/wiki/Protein_electrophoresishttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Beta-2_microglobulinhttp://en.wikipedia.org/wiki/Erythrocyte_sedimentation_ratehttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Anemia7/27/2019 Proposal Chemistry
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Micrograph showing my
PAS positive (dark pink/
pink - left of image). PA
Atypical plasma cell infil
bodies (H&E, 50x).
Workup
A 59 year-old patient presented wi
of the brain was performed lookin
revealed a lytic lesion in the left te
petrous temporal bones confirmed
Red arrows: lesion; green arrow: n
many in the skull and is consistent
The workup of suspected multip
of the skull, axial skeleton and p"lytic lesions" (with local disapp
rayas "punched-out lesions" (pe
sensitive than simple X-ray in thespecially when vertebral diseas
the size of soft tissue plasmacyto
workup of myeloma patients (noscan).
Abone marrow biopsy is usuallby plasma cells. This percentage
Immunohistochemistry (staining
can detect plasma cells which excell surface; myeloma cells are t
loma cast nephropathy in akidney biopsy. Hyal
ed - right of image). Myelomatous casts are PA
stain.
trate with both Russell (cytoplasmic) and Dutc
h a left facial droop and a known history of multipl
for a cerebral cause. The brain appeared normal.
poral bone (right side of image), and focused reco
a lytic lesion involving the mastoid segment of the
rmal contralateral facial nerve canal. The lytic lesio
ith a myeloma deposit.
e myeloma includes a skeletal survey. This is a
oximal long bones. Myeloma activity sometimearance of normal bone due to resorption), and
per pot skull). Magnetic resonance imaging (
e detection of lytic lesions, and may supersedeis suspected. Occasionally a CT scan is perfor
mas. Bone scans are typically not of any additi
new bone formation; lytic lesions not well visu
performed to estimate the percentage of boneis used in the diagnostic criteria for myeloma.
particular cell types using antibodies against su
press immunoglobulin in the cytoplasm and occpically CD56, CD38, CD138 positive and CD1
ine casts are
S negative (pale
er (nuclear)
myeloma. A CT
lose inspection
nstructions of the
facial nerve canal.
n was one of
series ofX-rays
s appear asn the skull X-
RI) is more
keletal survey,ed to measure
nal value in the
alized on bone
arrow occupied
rface proteins)
asionally on the9 and CD45
http://en.wikipedia.org/wiki/PAS_stainhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/PAS_stainhttp://en.wikipedia.org/wiki/PAS_stainhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/CD45http://en.wikipedia.org/wiki/CD19http://en.wikipedia.org/wiki/CD138http://en.wikipedia.org/wiki/CD38http://en.wikipedia.org/wiki/CD56http://en.wikipedia.org/wiki/Immunohistochemistryhttp://en.wikipedia.org/wiki/Diagnostic_criteriahttp://en.wikipedia.org/wiki/Bone_marrow_biopsyhttp://en.wikipedia.org/wiki/Bone_scanhttp://en.wikipedia.org/wiki/CT_scanhttp://en.wikipedia.org/wiki/Vertebralhttp://en.wikipedia.org/wiki/Magnetic_resonance_imaginghttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/Axial_skeletonhttp://en.wikipedia.org/wiki/X-rayhttp://en.wikipedia.org/wiki/Skeletal_surveyhttp://en.wikipedia.org/wiki/Facial_nervehttp://en.wikipedia.org/wiki/Petrous_portion_of_the_temporal_bonehttp://en.wikipedia.org/wiki/Temporal_bonehttp://en.wikipedia.org/wiki/Cerebrumhttp://en.wikipedia.org/wiki/Brainhttp://en.wikipedia.org/wiki/Computed_tomographyhttp://en.wikipedia.org/wiki/File:Multiple_myeloma_skull_CT_arrows.PNGhttp://en.wikipedia.org/wiki/File:Multiple_myeloma_skull_CT_arrows.PNGhttp://en.wikipedia.org/wiki/File:Russell_and_Dutcher_bodies.jpghttp://en.wikipedia.org/wiki/PAS_stainhttp://en.wikipedia.org/wiki/Kidney_biopsyhttp://en.wikipedia.org/wiki/Cast_nephropathyhttp://en.wikipedia.org/wiki/Micrograph7/27/2019 Proposal Chemistry
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negative.[citation needed][2]
Cytogenetics may also be performed in myeloma for prognostic purposes,
including a myeloma-specific FISH and Virtual Karyotype.
Other useful laboratory tests include quantitative measurement ofIgA, IgG, IgM
(immunoglobulins) to look for immune paresis, andbeta 2-microglobulin which provides
prognostic information. On peripheral blood smear the rouleaux formation ofred blood cells iscommonly seen, though this is not specific.
The recent introduction of a commercial immunoassay for measurement of free light chains
potentially offers an improvement in monitoring disease progression and response to treatment,
particularly where the paraprotein is difficult to measure accurately by electrophoresis (for
example in light chain myeloma, or where the paraprotein level is very low). Initial research alsosuggests that measurement of free light chains may also be used, in conjunction with other
markers, for assessment of the risk of progression from monoclonal gammopathy of
undetermined significance (MGUS) to multiple myeloma.[citation needed]
This assay, the serum free light chain assay, has recently been recommended by the InternationalMyeloma Working Groupfor the screening, diagnosis,prognosis, and monitoring of plasma cell
dyscrasias.
The prognosis of myeloma varies widely depending upon various risk factors. The Mayo Clinic
has developed a risk-stratification model termed Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART) which divides patients into high-risk and standard-risk categories.
Patients with deletion ofchromosome 13 or hypodiploidy by conventional cytogenetics, t(4;14),t(14;16) or17p- by molecular genetic studies, or with a high plasma cell labeling index (3% or
more) are considered to have high-risk myeloma.
Diagnostic criteria
In 2003, the International Myeloma Working Group[2]
agreed on diagnostic criteria forsymptomatic myeloma, asymptomatic myeloma and MGUS (monoclonal gammopathy of
undetermined significance), which was subsequently updated in 2009:[7]
Symptomatic myeloma:1. Clonal plasma cells >10% on bone marrowbiopsy or (in any quantity) in a biopsy from
other tissues (plasmacytoma)
2. A monoclonal protein (paraprotein) in either serum or urine (except in cases of truenon-secretory myeloma)
3. Evidence of end-organ damage felt related to the plasma cell disorder (related organ ortissue impairment, ROTI, commonly referred to by the acronym "CRAB"):
HyperCalcemia (corrected calcium >2.75 mmol/L) Renal insufficiency attributable to myeloma Anemia (hemoglobin
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amyloidosis should be considered as amyloidosis and not myeloma. CRAB like abnormalities
are common with numerous diseases, and it is imperative that these abnormalities are felt to be
directly attributable to the related plasma cell disorder and every attempt made to rule out otherunderlying causes of anemia, renal failure etc.
Asymptomatic (smoldering) myeloma:1. Serum paraprotein >30 g/L AND/OR
2. Clonal plasma cells >10% on bone marrow biopsy AND3. NO myeloma-related organ or tissue impairment
Monoclonal gammopathy of undetermined significance (MGUS):1. Serum paraprotein
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o Skeletal survey: normal or single plasmacytoma or osteoporosiso Serum paraprotein level < 5 g/dL if IgG, < 3 g/dL if IgAo Urinary light chain excretion < 4 g/24h
stage II: fulfilling the criteria of neither I nor III stage III: one or more of
o Hb < 8.5g/dLo high calcium > 12 mg/dLo Skeletal survey: Three or more lytic bone lesionso Serum paraprotein > 7g/dL if IgG, > 5 g/dL if IgAo Urinary light chain excretion > 12g/24h
Stages I, II, and III of the Durie-Salmon staging system can be divided into A or B depending on
serum creatinine:
A: serum creatinine < 2 mg/dL (< 177 umol/L) B: serum creatinine > 2 mg/dL (> 177 umol/L)
Pathophysiology
B lymphocytes start in the bone marrow and move to the lymph nodes. As they progress, they
mature and display different proteins on their cell surface. When they are activated to secrete
antibodies, they are known as plasma cells.
Multiple myeloma develops in B lymphocytes after they have left the part of the lymph node
known as the germinal center. The normal cell line most closely associated with MM cells isgenerally taken to be either an activated memory B cell or the precursor to plasma cells, the
plasmablast.[10]
The immune system keeps the proliferation of B cells and the secretion of antibodies under tight
control. When chromosomes and genes are damaged, often through rearrangement, this control is
lost. Often, a promoter gene moves (or translocates) to a chromosome where it stimulates anantibody gene to overproduction.
A chromosomal translocation between the immunoglobulin heavy chain gene (on chromosome14, locus q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11
[11]) is frequently
observed in patients with multiple myeloma. This mutation results in dysregulation of the
oncogene which is thought to be an important initiating event in the pathogenesis of myeloma.The result is proliferation of a plasma cell clone and genomic instability that leads to further
mutations and translocations. The chromosome 14 abnormality is observed in about 50% of allcases of myeloma. Deletion of (parts of) chromosome 13 is also observed in about 50% of cases.
Production ofcytokines[12]
(especially IL-6) by the plasma cells causes much of their localised
damage, such as osteoporosis, and creates a microenvironment in which the malignant cellsthrive. Angiogenesis(the attraction of new blood vessels) is increased.
http://en.wikipedia.org/wiki/Plasmablasthttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Chromosome_14http://en.wikipedia.org/wiki/Chromosome_14http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Angiogenesishttp://en.wikipedia.org/wiki/Osteoporosishttp://en.wikipedia.org/wiki/Interleukin_6http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Oncogenehttp://en.wikipedia.org/wiki/Chromosome_14http://en.wikipedia.org/wiki/Chromosome_14http://en.wikipedia.org/wiki/Heavy_chainhttp://en.wikipedia.org/wiki/Chromosomal_translocationhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Plasmablasthttp://en.wikipedia.org/wiki/Memory_B_cellhttp://en.wikipedia.org/wiki/Germinal_centerhttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/B_lymphocytes7/27/2019 Proposal Chemistry
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The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy
and various other myeloma-associated symptoms.
Treatment
Treatment for multiple myeloma is focused on therapies that decrease the clonal plasma cellpopulation and consequently decrease the signs and symptoms of disease. If the disease is
completely asymptomatic (i.e. there is a paraprotein and an abnormal bone marrow population
but no end-organ damage), as in smoldering myeloma, treatment is typically deferred, orrestricted to clinical trials.
[13]
In addition to direct treatment of the plasma cell proliferation,bisphosphonates (e.g.pamidronateorzoledronic acid) are routinely administered to prevent fractures; they have also been observed
to have direct anti-tumor effect even in patients without known skeletal disease. If needed, red
blood cell transfusions orerythropoietin can be used for management of anemia.
Initial therapy
Initial treatment of multiple myeloma depends on the patients age and comorbidities. In recentyears, high-dose chemotherapy with autologous hematopoietic stem-cell transplantation has
become the preferred treatment for patients under the age of 65. Prior to stem-cell
transplantation, these patients receive an initial course of induction chemotherapy. The mostcommon induction regimens used today are thalidomidedexamethasone,bortezomib based
regimens, and lenalidomidedexamethasone.[14][15]
Autologous stem cell transplantation (ASCT),
the transplantation of a patients own stem cells after chemotherapy, is the most common type ofstem cell transplantation for multiple myeloma. It is not curative, but does prolong overall
survival and complete remission. Allogeneic stem cell transplantation, the transplantation of a
healthy persons stem cells into the affected patient, has the potential for a cure, but is onlyavailable to a small percentage of patients.
[11]Furthermore, there is a 510% treatment-
associated mortality rate.
Patients over age 65 and patients with significant concurrent illness often cannot tolerate stem
cell transplantation. For these patients, the standard of care has been chemotherapy with
melphalan and prednisone. Recent studies among this population[16]
suggest improved outcomeswith new chemotherapy regimens, e.g. withbortezomib.
[17]Treatment with bortezomib,
melphalan, and prednisone had an estimated overall survival of 83% at 30 months, lenalidomide
plus low-dose dexamethasone an 82% survival at 2 years and melphalan, prednisone and
lenalidomide had a 90% survival at 2 years. Head-to-head studies comparing these regimens
have not been performed.[18]
A 2009 review noted "Deep venous thrombosis and pulmonary embolism are the major side
effects of thalidomide and lenalidomide. Lenalidomide causes more myelosuppression, and
thalidomide causes more sedation. Peripheral neuropathy and thrombocytopenia are major side
effects of bortezomib."[19]
http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Red_blood_cellhttp://en.wikipedia.org/wiki/Red_blood_cellhttp://en.wikipedia.org/wiki/Erythropoietinhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Bortezomibhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Melphalanhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Allogeneic_stem_cell_transplantationhttp://en.wikipedia.org/wiki/Autologous_stem_cell_transplantationhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Lenalidomidehttp://en.wikipedia.org/wiki/Bortezomibhttp://en.wikipedia.org/wiki/Dexamethasonehttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantationhttp://en.wikipedia.org/wiki/Erythropoietinhttp://en.wikipedia.org/wiki/Red_blood_cellhttp://en.wikipedia.org/wiki/Red_blood_cellhttp://en.wikipedia.org/wiki/Zoledronic_acidhttp://en.wikipedia.org/wiki/Pamidronatehttp://en.wikipedia.org/wiki/Bisphosphonatehttp://en.wikipedia.org/wiki/Multiple_myeloma7/27/2019 Proposal Chemistry
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Treatment of related hyperviscosity syndrome may be required to prevent neurologic symptoms
orrenal failure.[20][21]
Maintenance therapy
Sometimes after the initial treatment an ongoing maintenance therapy is offered. A 2009 reviewof maintenance therapy concluded "In younger patients, post-ASCT maintenance therapy with
thalidomide appears to increase tumor burden reduction further, which translates in[to]
prolonged PFS (Progression-free survival)."[22]
A different 2009 review stated "the role of maintenance therapy with thalidomide, lenalidomide,
or bortezomib for patients with multiple myeloma is not definitively established; such therapyshould be performed only in the context of a clinical trial."
[23]
Relapse
The natural history of myeloma is of relapse following treatment. Depending on the patient'scondition, the prior treatment modalities used and the duration of remission, options for relapseddisease include re-treatment with the original agent, use of other agents (such as melphalan,
cyclophosphamide, thalidomide or dexamethasone, alone or in combination), and a second
autologous stem cell transplant.
Later in the course of the disease, "treatment resistance" occurs. This may be a reversible
effect,[11]
and some new treatment modalities may re-sensitize the tumor to standard therapy. Forpatients with relapsed disease,bortezomib (or Velcade) is a recent addition to the therapeutic
arsenal, especially as second line therapy, since 2005. Bortezomib is aproteasome inhibitor.
Finally, lenalidomide (or Revlimid), a less toxic thalidomide analog, is showing promise for
treating myeloma. More and more patients survive longer and longer, thanks to stem celltransplant (with their own or a donor's) and treatments combining Bortezomib (Velcade),
Dexamethasone (corticoid) and melphalan or cyclophosphamide (Endoxan).This seems to
maintain the monoclonal peak at a reasonable level. Survival expectancy is then rising, and newtreatments are being developed.
Renal failure in multiple myeloma can be acute (reversible) orchronic (irreversible). Acute renalfailure typically resolves when the calcium and paraprotein levels are brought under control.
Treatment of chronic renal failure is dependent on the type of renal failure and may involve
dialysis.
Prognosis
With high-dose therapy followed by autologous stem cell transplantation, the median survival
has been estimated in 2003 to be approximately 4.5 years, compared to a median of
approximately 3.5 years with "standard" therapy.[24]
http://en.wikipedia.org/wiki/Renal_failurehttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Progression-free_survivalhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Medianhttp://en.wikipedia.org/wiki/Autologous_stem_cell_transplantationhttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/wiki/Chronic_renal_failurehttp://en.wikipedia.org/wiki/Acute_renal_failurehttp://en.wikipedia.org/wiki/Lenalidomidehttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Bortezomibhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Progression-free_survivalhttp://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Renal_failurehttp://en.wikipedia.org/wiki/Hyperviscosity_syndrome7/27/2019 Proposal Chemistry
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The International Staging Syste
of 62 months for stage 1 disease,
disease.[8]
The prognoses for patients with
for everyone. The average age oserious diseases, which affect su
Genetic testing
Some myeloma centers now em
examining DNA, oncologists careturning quickly following treat
Cytogenetic analysis of myelom13, non-hyperdiploidy and the b
prognosis. The 11q13 and 6p21
Prognostic markers such as thes
that new treatment developmentrisk" disease.
SNP array karyotyping can detecmissed by a targeted FISH panel
cytogenetics informative in only
1. Virtual karyotyping identifi2.
del(12p13.31) is an indepe
3. amp(5q31.1) is a favorable4. The prognostic impact of a
patients who greatly benef
Array-based karyotyping cannot
MM. Therefore, FISH for this tr
detect genome-wide copy numb
Epidemiology
can help to predict survival, with a median sur
45 months for stage 2 disease, and 29 months
ultiple myeloma, as those with other diseases,
onset is 70 years. Older patients often are expevival. Younger patients might have much long
loy genetic testing, which they call a gene arr
determine if patients are high risk or low riskment.
cells may be ofprognostic value, with deletiolanced translocations t(4;14) and t(14;16) conf
ytogenetic abnormalities are associated with a
are always generated by retrospective analyses
will improve the outlook for those with traditi
t copy number alterations of prognostic signific.[25]
In MM, lack of a proliferative clone makes
~30% of cases.
d chromosomal abnormalities in 98% of MM cases
dent adverse markermarker
p(5q31.1) over-rides that of hyperdiploidy and als
it from high-dose therapy.
detect balanced translocations, such as t(4;14) s
nslocation should also be performed if using S
r alterations of prognostic significance in MM.
vival (in 2005)
or stage 3
are not the same
riencing otherr survival rates.
y. By
f the cancer
of chromosomerring a poorer
etter prognosis.
, and it is likely
nally "poor-
ance that may beconventional
o identifies
een in ~15% of
P arrays to
http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/File:Lymphomas,_multiple_myeloma_world_map_-_Death_-_WHO2004.svghttp://en.wikipedia.org/wiki/File:Lymphomas,_multiple_myeloma_world_map_-_Death_-_WHO2004.svghttp://en.wikipedia.org/wiki/Virtual_Karyotypehttp://en.wikipedia.org/w/index.php?title=12p13.31&action=edit&redlink=1http://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Virtual_Karyotypehttp://en.wikipedia.org/wiki/Prognosishttp://en.wikipedia.org/wiki/Cytogenetichttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myeloma7/27/2019 Proposal Chemistry
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Age-standardized death fromlymphomas and multiple myeloma per 100,000 inhabitants in 2004.[26]
no data
less than 1.8
1.83.6
3.65.4
5.47.2
7.29
910.8
10.812.6
12.614.4
14.416.2
16.218
1819.8
more than 19.8
Multiple myeloma, globally, resulted in about 74,000 deaths in 2010 up from 49,000 in 1990.[27]
There are approximately 71,213 people in the United States living with multiple myeloma andaccording to Surveillance Epidemiology and End Results data an estimated 21,700 new cases of
myeloma were diagnosed in 2012 in the United States. The age-adjusted incidence rate for
multiple myeloma is 5.8 per 100,000 per year.
Multiple myeloma is the second most prevalent blood cancer (10%) afternon-Hodgkin's
lymphoma.[28]
It represents approximately 1% of all cancers and 2% of all cancer deaths.Although the peak age of onset of multiple myeloma is 65 to 70 years of age, recent
statistics[citation needed]
indicate both increasing incidence and earlier age of onset.
Multiple myeloma affects slightly more men than women. African Americans and Native Pacific
Islanders have the highest reported incidence of this disease in the United States and Asians thelowest. Results of a recent study found the incidence of myeloma to be 9.5 cases per 100,000African Americans and 4.1 cases per 100,000 Caucasian Americans. Among African Americans,
myeloma is one of the top 10 leading causes of cancer death.
A familial predisposition to myeloma exists.[29]
Hyperphosphorylation of a number of proteins -
the paratarg proteins - a tendency which is inherited in an autosomal dominant manner appears a
http://en.wikipedia.org/wiki/Age_adjustmenthttp://en.wikipedia.org/wiki/Lymphomashttp://en.wikipedia.org/wiki/Lymphomashttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Non-Hodgkin%27s_lymphomahttp://en.wikipedia.org/wiki/Non-Hodgkin%27s_lymphomahttp://en.wikipedia.org/wiki/Non-Hodgkin%27s_lymphomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Wikipedia:Citation_neededhttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Non-Hodgkin%27s_lymphomahttp://en.wikipedia.org/wiki/Non-Hodgkin%27s_lymphomahttp://en.wikipedia.org/wiki/Surveillance_Epidemiology_and_End_Resultshttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Multiple_myelomahttp://en.wikipedia.org/wiki/Lymphomashttp://en.wikipedia.org/wiki/Age_adjustment7/27/2019 Proposal Chemistry
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common mechanism in these familes. This tendency is more common in African American
patients with myeloma and may contribute to the higher rates of myeloma in this group.[29]
Other animals
Multiple myeloma affects many other species. The disease has been diagnosed in dogs,[30] cats,and horses.
[31]
In dogs, multiple myeloma accounts for around 8% of all haemopoietic tumors. Multiplemyeloma occurs in older dogs, and is not particularly associated with either males or females. No
species appear over represented in case reviews that have been conducted.[32]
Diagnosis in dogs
is usually delayed due to the initial non specificity and range of clinical signs possible. Diagnosisusually involves bone marrow studies, X-rays, and plasma protein studies. In dogs, protein
studies usually reveal the monoclonal gammaglobulin elevation to be IgA or IgG in equal
incidence.[32]
In rare cases the globulin elevation is IgM, which is referred to as Waldenstrm's
macroglobulinemia.[33]
The prognosis for initial control and return to good quality of life in dogs
is good. 43% of dogs started on a combination chemotheraputic protocol achieved completeremission. Long term survival is normal with a median of 540 days reported.
[32]Recurrence is
expected eventually, and although rescue protocols can be attempted, recurrences are oftenresistant to available chemotheraputics, and death commonly eventually follows from
complications such as renal failure, sepsis or pain related owner initiated euthanasia.
See also
Discovery and development of thalidomide and its analogs Waldenstrm macroglobulinemia Plasma cell leukemia, an aggressive form of MM Multiple Myeloma Research Consortium Multiple Myeloma Research Foundation International Myeloma Foundation Virtual Karyotype
References
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