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

search Multiple myeloma Classification and external resources Micrograph of a plasmacytoma. the histologic correlate of multiple myeloma.[1] In multiple myeloma. Most cases of myeloma also feature the production of a paraprotein—an abnormal antibody which can cause kidney problems. collections of abnormal plasma cells accumulate in the bone marrow.0 203. the free encyclopedia Jump to: navigation.[1] .From Wikipedia. is a cancer of plasma cells. where they interfere with the production of normal blood cells.0 M9732/3 254500 8628 000583 med/1521 D009101 Multiple myeloma (from Greek myelo-. bone marrow). also known as plasma cell myeloma or Kahler's disease (after Otto Kahler). H&E stain ICD-10 ICD-9 ICD-O: OMIM DiseasesDB MedlinePlus eMedicine MeSH C90. Bone lesions and hypercalcemia (high calcium levels) are also often encountered. a type of white blood cell normally responsible for producing antibodies.

With conventional treatment.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. and constitutes 1% of all cancers. Multiple myeloma is the second most common hematological malignancy in the U.3 Renal failure o 1.3 Diagnostic criteria o 2.[1] Myeloma develops in 1–4 per 100. immunomodulatory drugs (IMiDs) such as thalidomide or lenalidomide.4 Staging 3 Pathophysiology 4 Treatment o 4.[1] Contents           1 Signs and symptoms o 1.2 Workup o 2. chemotherapy.000 people per year. It is more common in men. (after non-Hodgkin lymphoma).2 Maintenance therapy o 4.1 Investigations o 2. Radiation therapy is sometimes used to reduce pain from bone lesions. R = Renal failure. urine protein electrophoresis. A mnemonic sometimes used to remember the common tetrad (four parts) of multiple myeloma is CRAB: C = Calcium (elevated).S. and X-rays of commonly involved bones. median survival is 3–4 years. which may be extended to 5–7 years or longer with advanced treatments. bortezomib).3 Relapse 5 Prognosis o 5. and stem cell transplants.5 Neurological symptoms 2 Diagnosis o 2.1 Bone pain o 1. B = Bone lesions. and for unknown reasons is twice as common in African-Americans as it is in European-Americans.Myeloma is diagnosed with blood tests (serum protein electrophoresis.[2] Myeloma . the symptoms and signs vary greatly.g. Remissions may be induced with steroids. serum free kappa/lambda light chain assay). proteasome inhibitors (e. A = Anemia.2 Infection o 1.1 Initial therapy o 4. Myeloma is generally thought to be incurable but highly treatable.4 Anemia o 1. bone marrow examination.

RANKL activates osteoclasts. leading to hypercalcemia and its associated symptoms.[4] The he increased risk of infection is due to immune deficiency. and K. Myeloma bone disease sease is due to the overexpression of Receptor Activator for Nuclear Factor κ B Ligand (RANKL RANKL) ) by bone marrow stroma. Bone pain affects almost 70% of patients and is the most common symptom. the majority of the antibodies are ineffective monoclonal antibodies from the clonal plasma cell.[3] Myeloma bone pain usually involves the spine and ribs. S. coli and other gram-negative organisms. A selected group of patients . which may show "punched-out" "punched out" resorptive lesions (including the "pepper pot" appearance of the skull on radiography). pneumoniae. pneumoniae. Common pneumonia pathogens include S. Infection The most common infections are pneumonias and pyelonephritis. The resultant bone lesions are lytic (cause breakdown) in nature and are best seen in plain radiographs. . while common pathogens causing pyelonephritis include E. incidence Bone pain Illustration showing the most common site of bone lesions in vertebrae. fracture Involvement of the vertebrae may lead to spinal cord compression. and all symptoms may be due to other causes. They are presented here in decreasing order of incidence. aureus.has many possible symptoms. See full animation animation. Persistent localized pain may indicate a pathological bone fracture. Although the total immunoglobulin level is typically elevated in multiple myeloma. The greatest risk period for the occurrence of infection is in the initial few months after the start of chemotherapy. and worsens with activity. The breakdown of bone also leads to release of calcium into the blood. which resorb bone.

It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis hematopoiesis) by cytokines. Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis thereby contributing to the renal failure. The most common cause of renal failure in Multiple Myeloma is due to tubulopathic effects of the light chains. ). Diagnosis Investigations Serum protein electrophoresis showing a paraprotein (peak in the gamma zone) in a patient with multiple myeloma. Finally. Headache Headache. It may give rise to paraplegia in late presenting cases. there may be radicular pain. . hyperuricemia recurrent infections (pyelonephritis). Other causes include hyperuricemia. . Amyloidosis is a distant third in the causation. weakness confusion and fatigue due to hypercalcemia. visual changes and retinopathy may be the result of hyperviscosity of the blood depending ding on the properties of the paraprotein. and local infiltration of tumor cells. Anemia The anemia found in myeloma is usually normocytic and normochromic.[5] Renal failure Renal failure may develop both acutely and chronically. . Neurological symptoms Common problems are weakness. Light chains produce myriad effects which can manifest as the Fanconi syndrome (type II renal tubular acidosis). loss of bowel or bladder control (due to involvement of spinal cord leading to cord compression) or carpal tunnel syndrome and other neuropathies (due to infiltration of peripheral nerves by amyloid amyloid).with documented hypogammaglobulinemia may benefit from replacement immunoglobulin therapy to reduce the risk of infection.

In theory. Tamm-Horsfall protein and albumin. The paraprotein is an abnormal immunoglobulin produced by the tumor clone. γ-. raised serum creatinine due to reduced renal function. releasing calcium into the bloodstream). with or without reduction of the other (normal) immunoglobulins (known as immune paresis). which might show the presence of a paraprotein (monoclonal protein. light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ. The globulin level may be normal in established disease. A doctor will request protein electrophoresis of the blood and urine. the myeloma is nonsecretory (not producing immunoglobulins). In addition. elevated beta-2 microglobulin. Quantitative measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease. H&E stain. lytic bone lesions.or λ-light chains or any of the five types of heavy chains (α-. a high erythrocyte sedimentation rate (ESR). H&E stain. δ-. but IgG paraproteins are most common. kidney dysfunction. ε.[6]  Bone marrow aspirate showing the histologic correlate of multiple myeloma under the microscope. IgD and IgE myeloma are very rare. followed by IgA and IgM.  Plasmacytoma. and/or a high serum protein (especially raised globulins or immunoglobulin) may prompt further testing.The presence of unexplained anemia. which is mainly due to casts of paraprotein deposition in the kidney.  . Very rarely.or μ-heavy chains). although the cast may also contain complete immunoglobulins. One type of paraprotein is the Bence Jones protein which is a urinary paraprotein composed of free light chains (see below). or M protein) band. Additional findings include: a raised calcium (when osteoclasts are breaking down bone. multiple myeloma can produce all classes of immunoglobulin.

tomas. Close inspection revealed a lytic lesion in the left temporal bone (right side of image). PAS stain. The lytic lesion was one of many in the skull and is consistent with a myeloma deposit.left of image). Occasionally a CT scan is performed to measure the size of soft tissue plasmacytomas. 50x). and focused reconstructions of the petrous temporal bones confirmed a lytic lesion les involving the mastoid segment of the facial nerve canal. A CT of the brain was performed looking for a cerebral cause.right of image). Bone scans are typically not of any additional value in the workup of myeloma patients (no new bone formation. green arrow: normal contralateral facial nerve canal. Myelomatous casts are PAS negative (pale pink . The brain appeared normal. Immunohistochemistry (staining particular cell types using antibodies against surface proteins) can detect plasma cells which express immunoglobulin in the cytoplasm and occasionally on the cell surface. stain  Atypical plasma cell infiltrate with both Russell (cytoplasmic) and Dutcher (nuclear) bodies (H&E. This is a series of X-rays of the skull. Magnetic resonance imaging (MRI) is more sensitive than simple X-ray ray in the detection of lytic lesions. especially when vertebral disease is suspected. .Micrograph showing myeloma cast nephropathy in akidney biopsy. Workup A 59 year-old old patient presented with a left facial droop and a known history of multiple myeloma. Myeloma activity sometimes appear as "lytic lesions" (with local disappearance of normal bone due to resorption). Red arrows: lesion. CD38. CD138 positive and CD19 and CD45 . This percentage is used in the diagnostic criteria for myeloma. lytic lesions not well visualized on bone scan). . myeloma cells are typically CD56. Hyaline casts are PAS positive (dark pink/red . and on the skull Xray as "punched-out out lesions" (pepper pot skull). The workup of suspected multiple myeloma includes a skeletal survey. A bone marrow biopsy is usually performed to estimate the percentage of bone marrow occupied by plasma cells. and may supersede skeletal survey. axial skeleton and proximal long bones.

[citation needed] This assay. t(14. Clonal plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma) 2. particularly where the paraprotein is difficult to measure accurately by electrophoresis (for example in light chain molecular genetic studies. and beta 2-microglobulin which provides prognostic information. The prognosis of myeloma varies widely depending upon various risk factors. for assessment of the risk of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.negative. ROTI. A monoclonal protein (paraprotein) in either serum or urine (except in cases of true non-secretory myeloma) 3. On peripheral blood smear the rouleaux formation of red blood cells is commonly seen. including a myeloma-specific FISH and Virtual Karyotype. the International Myeloma Working Group[2] agreed on diagnostic criteria for symptomatic myeloma.16) or 17p. Evidence of end-organ damage felt related to the plasma cell disorder (related organ or tissue impairment.75 mmol/L)  Renal insufficiency attributable to myeloma  Anemia (hemoglobin <10 g/dL)  Bone lesions (lytic lesions or osteoporosis with compression fractures) Note: Recurrent infections alone in a patient who has none of the CRAB features is not sufficient to make the diagnosis of myeloma. and monitoring of plasma cell dyscrasias. or where the paraprotein level is very low). Patients with deletion of chromosome 13 or hypodiploidy by conventional cytogenetics. which was subsequently updated in 2009:[7]  Symptomatic myeloma: 1.[citation needed][2] Cytogenetics may also be performed in myeloma for prognostic purposes. Other useful laboratory tests include quantitative measurement of IgA. asymptomatic myeloma and MGUS (monoclonal gammopathy of undetermined significance). IgM (immunoglobulins) to look for immune paresis. t(4. Initial research also suggests that measurement of free light chains may also be used. in conjunction with other markers. diagnosis. the serum free light chain assay. Patients who lack CRAB features but have evidence of . though this is not specific. Diagnostic criteria In 2003. 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. or with a high plasma cell labeling index (3% or more) are considered to have high-risk myeloma.14). commonly referred to by the acronym "CRAB"):  HyperCalcemia (corrected calcium >2. The Mayo Clinic has developed a risk-stratification model termed Mayo Stratification for Myeloma and Riskadapted Therapy (mSMART) which divides patients into high-risk and standard-risk categories. IgG. prognosis. has recently been recommended by the International Myeloma Working Group for the screening.

It does not really quantify tumor burden or extent unlike staging systems used in other cancers. NO myeloma-related organ or tissue impairment Monoclonal gammopathy of undetermined significance (MGUS): 1.amyloidosis should be considered as amyloidosis and not myeloma. Serum paraprotein >30 g/L AND/OR 2.5 g/dL. CRAB like abnormalities are common with numerous diseases. For this reason. endocrinopathy.5–5. 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 other underlying causes of anemia.   Asymptomatic (smoldering) myeloma: 1.5 g/dL Stage II: β2M < 3. It is more of a prognostic index rather than a true staging system. e. albumin ≥ 3.5 mg/L and albumin < 3. monoclonal plasma cell disorder. This is one of the main drawbacks of the ISS. or β2M 3. typically treated with irradiation).5 mg/L.5 mg/L irrespective of the serum albumin Stage III: β2M ≥ 5. Patients with MGUS and asymptomatic myeloma who have renal dysfunction from unrelated causes such as diabetes or hypertension may have elevated β2M levels just from the renal dysfunction and cannot be considered as stage III myeloma. organomegaly. and POEMS syndrome (peripheral neuropathy. Serum paraprotein <30 g/L AND 2. it is recommended that the ISS be used along with the Durie Salmon Staging System (see below).5 mg/L Note that the ISS should be used only in patients who meet diagnostic criteria for myeloma. Clonal plasma cells <10% on bone marrow biopsy AND 3. AL amyloidosis). NO myeloma-related organ or tissue impairment Related conditions include solitary plasmacytoma (a single tumor of plasma cells. Clonal plasma cells >10% on bone marrow biopsy AND 3.g. Staging International Staging System The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group in 2005:[8]    Stage I: β2-microglobulin (β2M) < 3. Durie-Salmon staging system First published in 1975. renal failure etc. plasma cell dyscrasia (where only the antibodies produce symptoms. the Durie-Salmon staging system[9] is still in use:  stage I: all of o Hb > 10g/dL o normal calcium . skin changes).

When they are activated to secrete antibodies. 16q23 and 20q11[11]) is frequently observed in patients with multiple myeloma. II. often through rearrangement.5g/dL o high calcium > 12 mg/dL o Skeletal survey: Three or more lytic bone lesions o Serum paraprotein > 7g/dL if IgG. they are known as plasma cells. such as osteoporosis. The normal cell line most closely associated with MM cells is generally taken to be either an activated memory B cell or the precursor to plasma cells. 4p16. Multiple myeloma develops in B lymphocytes after they have left the part of the lymph node known as the germinal center. locus q32) and an oncogene (often 11q13. 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. > 5 g/dL if IgA o Urinary light chain excretion > 12g/24h o o o Stages I. Deletion of (parts of) chromosome 13 is also observed in about 50% of cases. The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. As they progress. This mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of myeloma. 6p21. Angiogenesis (the attraction of new blood vessels) is increased. A chromosomal translocation between the immunoglobulin heavy chain gene (on chromosome 14. The result is proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations. the plasmablast.  Skeletal survey: normal or single plasmacytoma or osteoporosis Serum paraprotein level < 5 g/dL if IgG. this control is lost. Often. and creates a microenvironment in which the malignant cells thrive. .[10] The immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. a promoter gene moves (or translocates) to a chromosome where it stimulates an antibody gene to overproduction.3. they mature and display different proteins on their cell surface. Production of cytokines[12] (especially IL-6) by the plasma cells causes much of their localised damage. < 3 g/dL if IgA 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. When chromosomes and genes are damaged.

bortezomib based regimens. Treatment Treatment for multiple myeloma is focused on therapies that decrease the clonal plasma cell population and consequently decrease the signs and symptoms of disease. as in smoldering myeloma. lenalidomide plus low-dose dexamethasone an 82% survival at 2 years and melphalan. The most common induction regimens used today are thalidomide–dexamethasone. melphalan. In recent years. leading to renal failure. red blood cell transfusions or erythropoietin can be used for management of anemia.[18] A 2009 review noted "Deep venous thrombosis and pulmonary embolism are the major side effects of thalidomide and lenalidomide. high-dose chemotherapy with autologous hematopoietic stem-cell transplantation has become the preferred treatment for patients under the age of 65. has the potential for a cure. polyneuropathy and various other myeloma-associated symptoms. pamidronate or zoledronic acid) are routinely administered to prevent fractures. but is only available to a small percentage of patients. bisphosphonates (e. prednisone and lenalidomide had a 90% survival at 2 years. For these patients. treatment is typically deferred. Allogeneic stem cell transplantation. Lenalidomide causes more myelosuppression. and lenalidomide–dexamethasone. or restricted to clinical trials.g.The produced antibodies are deposited in various organs."[19] . Peripheral neuropathy and thrombocytopenia are major side effects of bortezomib. there is a 5–10% treatmentassociated mortality rate. there is a paraprotein and an abnormal bone marrow population but no end-organ damage). these patients receive an initial course of induction chemotherapy. If the disease is completely asymptomatic (i. the transplantation of a patient’s own stem cells after chemotherapy.[11] Furthermore. the standard of care has been chemotherapy with melphalan and prednisone. e. but does prolong overall survival and complete remission. and thalidomide causes more sedation. If needed.[13] In addition to direct treatment of the plasma cell proliferation. It is not curative. they have also been observed to have direct anti-tumor effect even in patients without known skeletal disease. and prednisone had an estimated overall survival of 83% at 30 months. with bortezomib.e. the transplantation of a healthy person’s stem cells into the affected patient. Initial therapy Initial treatment of multiple myeloma depends on the patient’s age and comorbidities. Head-to-head studies comparing these regimens have not been performed.[14][15] Autologous stem cell transplantation (ASCT).g.[17] Treatment with bortezomib. Recent studies among this population[16] suggest improved outcomes with new chemotherapy regimens. Prior to stem-cell transplantation. Patients over age 65 and patients with significant concurrent illness often cannot tolerate stem cell transplantation. is the most common type of stem cell transplantation for multiple myeloma.

Survival expectancy is then rising. which translates in[to] prolonged PFS (Progression-free survival). bortezomib (or Velcade) is a recent addition to the therapeutic arsenal.[11] and some new treatment modalities may re-sensitize the tumor to standard therapy. lenalidomide. lenalidomide (or Revlimid). Finally.[20][21] Maintenance therapy Sometimes after the initial treatment an ongoing maintenance therapy is offered.[24] .5 years with "standard" therapy. thanks to stem cell transplant (with their own or a donor's) and treatments combining Bortezomib (Velcade).This seems to maintain the monoclonal peak at a reasonable level. Dexamethasone (corticoid) and melphalan or cyclophosphamide (Endoxan). Depending on the patient's condition. and new treatments are being developed.5 years. A 2009 review of maintenance therapy concluded "In younger patients. is showing promise for treating myeloma. a less toxic thalidomide analog. More and more patients survive longer and longer. especially as second line therapy. cyclophosphamide. alone or in combination). Later in the course of the disease. such therapy should be performed only in the context of a clinical trial. options for relapsed disease include re-treatment with the original agent. the prior treatment modalities used and the duration of remission. and a second autologous stem cell transplant. compared to a median of approximately 3. Acute renal failure typically resolves when the calcium and paraprotein levels are brought under control. This may be a reversible effect."[23] Relapse The natural history of myeloma is of relapse following treatment. use of other agents (such as melphalan. the median survival has been estimated in 2003 to be approximately 4. post-ASCT maintenance therapy with thalidomide appears to increase tumor burden reduction further. Bortezomib is a proteasome inhibitor. or bortezomib for patients with multiple myeloma is not definitively established. Renal failure in multiple myeloma can be acute (reversible) or chronic (irreversible). since 2005. Prognosis With high-dose therapy followed by autologous stem cell transplantation. thalidomide or dexamethasone. "treatment resistance" occurs. For patients with relapsed disease."[22] A different 2009 review stated "the role of maintenance therapy with thalidomide.Treatment of related hyperviscosity syndrome may be required to prevent neurologic symptoms or renal failure. Treatment of chronic renal failure is dependent on the type of renal failure and may involve dialysis.

are not the same for everyone.[8] The prognoses noses for patients with multiple myeloma.14) seen in ~15% of MM. Prognostic markers such as these are always generated by retrospective analyses. . The average age of onset is 70 years. Genetic testing Some myeloma centers now employ genetic testing. FISH for this translocation should also be performed if using SNP arrays to detect genome-wide wide copy number alterations of prognostic prog significance in MM. Array-based karyotyping cannot detect balanced translocations. 1. Therefore.14) and t(14. Epidemiology . such as t(4. 2.[25] In MM. 45 months for stage 2 disease. which affect survival. which they call a “gene array. with deletion of chromosome 13.31) ) is an independent adverse marker amp(5q31. and 29 months for stage 3 disease. and it is likely that new treatment developments will improve the outlook for those with traditionally "poor "poorrisk" disease. as those with other diseases. The 11q13 and 6p21 cytogenetic abnormalities are associated with a better prognosis.” By examining DNA. 3. non-hyperdiploidy y and the balanced translocations t(4. Older patients often are experiencing other serious diseases.1) is a favorable marker The prognostic impact of amp(5q31.16) conferring a poorer prognosis.1) over-rides over rides that of hyperdiploidy and also identifies patients who greatly benefit from high-dose high therapy. oncologists can determine if patients are high risk or low risk of the cancer returning quickly following treatment.The International Staging System can help to predict survival. SNP array karyotyping can detect copy number alterations alterations of prognostic significance that may be missed by a targeted FISH panel. lack of a proliferative clone makes conventional cytogenetics informative in only ~30% of cases. with a median survival (in 2005) of 62 months for stage 1 disease. Virtual karyotyping identified chromosomal abnormalities in 98% of MM cases del(12p13. Younger patients might have much much longer survival rates. treatment Cytogenetic analysis of myeloma cells may be of prognostic value. 4.

Although the peak age of onset of multiple myeloma is 65 to 70 years of age.000 African Americans and 4.6–14. recent statistics[citation needed] indicate both increasing incidence and earlier age of onset. globally. myeloma is one of the top 10 leading causes of cancer death.8–12. The age-adjusted incidence rate for multiple myeloma is 5. Among African Americans.000 per year.4 5.6 12.8–3. Results of a recent study found the incidence of myeloma to be 9.000 deaths in 2010 up from 49.000 inhabitants in 2004.8 10.6 3. resulted in about 74.[29] Hyperphosphorylation of a number of proteins the paratarg proteins .Age-standardized death from lymphomas and multiple myeloma per 100.000 in 1990.700 new cases of myeloma were diagnosed in 2012 in the United States.4–7.4–16.2 7.[26] no data less than 1.2–9 9–10.[27] There are approximately 71.213 people in the United States living with multiple myeloma and according to Surveillance Epidemiology and End Results data an estimated 21.4 14.5 cases per 100.a tendency which is inherited in an autosomal dominant manner appears a .2–18 18–19.[28] It represents approximately 1% of all cancers and 2% of all cancer deaths.1 cases per 100. Multiple myeloma is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma.6–5.8 per 100.8 more than 19. Multiple myeloma affects slightly more men than women.000 Caucasian Americans. African Americans and Native Pacific Islanders have the highest reported incidence of this disease in the United States and Asians the lowest.8 Multiple myeloma. A familial predisposition to myeloma exists.8 1.2 16.

sepsis or pain related owner initiated euthanasia. protein studies usually reveal the monoclonal gammaglobulin elevation to be IgA or IgG in equal incidence. PMC 1550368.[32] Recurrence is expected eventually. Mc Graw Hill Medical. and plasma protein studies. Dan (2012). This tendency is more common in African American patients with myeloma and may contribute to the higher rates of myeloma in this group. 938. and although rescue protocols can be attempted. X-rays. Podar K.[29] Other animals Multiple myeloma affects many other species. 4. Br. ISBN 978-0-07-174889-6. multiple myeloma and related disorders: a report of the International Myeloma Working Group". PMID 8033429. Lee M (1994). Lancet 374 (9686): 324–39. ^ a b c International Myeloma Working Group (2003). J.x. Anderson KC (July 2009). and death commonly eventually follows from complications such as renal failure. No species appear over represented in case reviews that have been conducted.[32] In rare cases the globulin elevation is IgM. 3. In dogs.[32] Diagnosis in dogs is usually delayed due to the initial non specificity and range of clinical signs possible. multiple myeloma accounts for around 8% of all haemopoietic tumors. Multiple myeloma occurs in older dogs. doi:10. 121 (5): 749–57. doi:10. 43% of dogs started on a combination chemotheraputic protocol achieved complete remission. PMID 19541364. which is referred to as Waldenström's macroglobulinemia.[31] In dogs.04355. and is not particularly associated with either males or females.13652141. See also        Discovery and development of thalidomide and its analogs Waldenström macroglobulinemia Plasma cell leukemia. an aggressive form of MM Multiple Myeloma Research Consortium Multiple Myeloma Research Foundation International Myeloma Foundation Virtual Karyotype References 1.[33] The prognosis for initial control and return to good quality of life in dogs is good. Diagnosis usually involves bone marrow studies. "Criteria for the classification of monoclonal gammopathies. Clin. ^ Longo. Harrison's Principles of Internal Medicine 18th Edition. Immunol.2003. 2. ^ a b c d Raab MS. ^ Chapel HM. Haematol. Long term survival is normal with a median of 540 days reported. PMID 12780789. "Multiple myeloma".[30] cats.common mechanism in these familes. "The use of intravenous immune globulin in multiple myeloma". and horses. recurrences are often resistant to available chemotheraputics. The disease has been diagnosed in dogs. 97 (Suppl 1): 21–4. Breitkreutz I. p. Richardson PG. Exp.1016/S0140-6736(09)60221-X. .1046/j.

Leukemia 23 (1): 3–9. doi:10. J. ^ Kyle RA. 7. p. 23. PMID 15509819. PMC 2627786. ^ San Miguel. McKeage K.CO. ^ Paul M. 12. PMID 7139441. Richard Sheppard.1016/S1548-5315(11)70208-X. PMC 1862296. N. doi:10. doi:10. PMC 2265446. Bear RA (November 1982). 15. 2009.1182/blood-2011-01-270140. ^ Curran M. ^ "Managing the side effects of lenalidomide and bortezomib" (PDF). ISBN 3-8055-6460-0.V. 17. Kumar. ^ Harousseau J. (2008). PMID 7730490. doi:10. 8. Rajkumar SV (January 2009). "International staging system for multiple myeloma". J. doi:10. "Multiple myeloma". (2009). Community Oncology 6 (2): 53. 11. ^ Abraham J (2009). doi:10. 359 (9): 906–917. Oncol. "Advances in multiple myeloma treatment: lenalidomide and bortezomib" (PDF). 6. ^ Multiple myeloma chemotherapy regimens 16.5. Robbins Basic Pathology (8th ed.). Chemical Immunology 67. Arch. "Maintenance therapy in multiple myeloma".3. 10. Med. R. and chemotherapy". PMID 18753647. ^ Federico Caligaris-Cappio.242.2-U. 19.. Abbas. ^ Durie BG. Drugs 69 (7): 859–888. et al. Plasmapheresis. Blood. Landgren O (2011). Pineda AA.1182/blood-2007-10-078022. Switzerland: S. Clin.2009. 21.1002/1097-0142(197509)36:3<842::AIDCNCR2820360303>3.1200/JCO. Med.e12. ^ Kyle.-L. doi:10.1136/jcp. et al.1056/NEJMoa0801479. PMID 15809451. Engl. "New insights into role of microenvironment in multiple myeloma. 20.. PMID 18753654. (1995). PMID 21441462. J. (2009). San Miguel J. doi:10. 23 (15): 3412–20. "Multiple myeloma". "Treatment of Myeloma — Are We Making Progress?". Community Oncology: 58. J. ^ Mitchell. J. Intern.G. ^ Johnson WJ. doi:10. J. N. Philadelphia: Saunders.F.1056/NEJMe0805176.2005. doi:10. ^ Hargreaves RM. doi:10.1016/S0140-6736(00)00019-2. Manlio Ferrarini (1997). Hematology Reviews 1 (2): e12. Pathol. "Treatment of renal failure associated with multiple myeloma. PMC 502468. ^ Korde N.1056/NEJMra041875. Salmon SE (1975).291. doi:10. ^ a b c Kyle RA. Engl. (2008). risk stratification and response assessment of multiple myeloma". (2005). 105. PMC 3316455. 14. 18.4081/hr. 150 (4): 863–9. Cancer 36 (3): 842–54.1001/archinte. et al. 48 (3): 260–6. "Immunological factors and risk of infection in plateau phase myeloma (stable phase)" (PDF). Lea JR. ^ a b Greipp PR. Abul K. Walker F. hemodialysis. "A clinical staging system for multiple myeloma. B. Durie BG. Med. Karger AG. 9. 455. . doi:10. S. Blood (journal) 117 (21): 5573–5581. Can Med Assoc J 127 (10): 956. "Multiple myeloma".0. PMID 18971951. 13. Lancet 355 (9200): 248–50. "Plasmapheresis therapy in a patient with multiple myeloma". N.260. staging. Fausto. 111 (6): 2962–72. Holley KE (April 1990). doi:10. Kristinsson SY.2008. "Criteria for diagnosis. PMID 18332230.M. Med.1038/leu. Engl.48. PMID 2183734. response to treatment.1990. ISBN 1-4160-29737. "Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma". Nelson.". Human B Cell Populations. PMID 10675068. Kyle RA. "Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies". "Bortezomib: A Review of its Use in Patients with Multiple Myeloma". Vinay. Correlation of measured myeloma cell mass with presenting clinical features. (2008). doi:10. 359 (9): 964–6. p.2165/00003495-200969070-00006.2165/00003495-200969070-00006. Rajkumar. 22.00390160111022. Clin. Rajkumar SV (2004). O'Brien PC. PMID 1182674. ^ Durie.A. PMID 19441872. ^ Tricot G (2000). 351 (18): 1860–73.04. Griffiths H. and survival".

^ Collins CD (2005). Clin. Ther Adv Hematol 4 (4): 291–7.G. doi:10.E. Feldman. Am.20. Vet. 28. ^ Ettinger. R (2012 Dec 15). PMID 19687334. W. Saunders. "Inherited predisposition to multiple myeloma". ^ "WHO Disease and injury country estimates". E. PMC 1665317. N. 191 (3): 337–9. E. "Multiple myeloma in a horse". [Stem Cell Transplantation for Multiple Myeloma: High-Dose Therapy and Stem Cell Transplantation Lay summary] – Medscape. Stephen J. PMID 3721983 33.0033. ISBN 978-0-7216-7257-1. PMC 2754906. ^ a b Koura DT. Med. PMID 12736280.. doi:10. Morgan GJ.2008. ^ Child JA. 32. Med. Retrieved Nov.G. "Prognostic significance of copynumber alterations in multiple myeloma". Engl. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 1. Lancet 380 (9859): 2095–128. J Am Vet Med Assoc 11 (188): 1288–92. Qualls C. MacEwen. "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.E.6136.. Cancer Imaging 5 (Spec No A): S119–26.1102/1470-7330. Li C. 27 (27): 4585–90.1177/2040620713485375. 27.". Tyler R. 516–9. PMID 3654300. 348 (19): 1875–83. PMID 23926460. A. C. 2009.. Magrangeas F. Leifer. (1977). ^ Lozano.1200/JCO. PMID 23245604. World Health Organization.2005.I. doi:10. 31. 25. Edward C. J. R. Davies FE. pp. 30..I. (September 2009). "High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma". ^ a b c Matus. Oncol. 29. A. Langston AA (August 2013). ^ MacEwan. 11. Vet Clin North American Small Animal Practice 7: 119 .24. "Problems monitoring response in multiple myeloma". PMID 16361127.B. J. ^ MacAllister C.. ^ Avet-Loiseau H. "Diagnosis and Management of Monoclonal Gammopathies". Hurvitz. Assoc. (May 2003). J. doi:10.1056/NEJMoa022340. Root CR (August 1987). 2009. 26. "Prognostic factors for multiple myeloma in the dog". et al. (1986). (1 June 2000). Hurvitz. et al.

Sign up to vote on this title
UsefulNot useful