Renal Failure in Multiple Myeloma Tutorial MSN 621

Renal Failure in Multiple Myeloma Tutorial/ MSN 621 Beth St John BSN Alverno College

Purpose and Objectives �Purpose: �To educate RNs and LPNs on the underlying disease process of multiple myeloma and how it leads to renal failure �Objectives: �Review pathophysiology of renal failure in multiple myeloma �Identify key assessment components of multiple myeloma patient in renal failure �Describe interventions for management of multiple myeloma patient in renal failure, emphasizing nursing sensitive patient outcomes.

Normal Renal Function 2 Kidneys –located back of the body in the abdominal cavity contains: nephrons, glomerulus, and tubules kidney glomerulus � nephron tubules � used with permission Wellcome, Library, London

Function of the Kidney: �Remove waste products �Regulate body fluids and electrolytes �Produces hormones �Regulate blood pressure �Excrete drugs and toxins Lancaster, L. (Ed. ). (2001). Core Curriculum for Nephrology Nursing (4 th ed. ). Pitman, NJ: American Nephrology Nurses' Association.

Function of the Kidney Remove waste products �Urea : product of protein metabolism; an excess is a sign of uremia �Creatinine: end product of creatine metabolism; an excess is a sign of advanced kidney disease �Uric acid: an end product of purine metabolism, must be excreted because the body cannot destroy it; an excess can cause gout �Beta 2 microglobulin: an end product of Class I HLAs; complement proteins activation can lead to increase of microglobulins; Lancaster, L. (Ed. ). (2001). Core Curriculum for Nephrology Nursing (4 th ed. ). Pitman, NJ: American Nephrology Nurses' Association Porth, C. , & Matfin, G. (Eds. ). (2009). Pathophysiology: Concepts of altered health states (8 th ed. ). Philadelphia: Wolters Kluwer Health/ Lippincott Williams & Wilkins

Function of the Kidney: �Regulate body fluids and electrolytes � Key systems help to maintain function �Cardiovascular: provides plasma to help regulate water and electrolytes �Nervous: helps fluid balance by regulating thirst �Endocrine: produces hormones to alter water absorption

Function of the Kidney: �Produces hormones � Prostaglandins; “a group of mediators of cell function” (Porth & Matfin, 2009 p. 749), produce vasodilatation, “protects the kidney against the vasoconstricting effects of sympathetic stimulation and angiotensin II “(Porth & Matfin, 2009 p. 749) � Erythropoietin: a hormone that stimulates production of RBCs; secreted in response to renal hypoxia and possibly epinephrine, norepinephrine and prostaglandins � 1, 25 – dihydroxycholecaciferol (activated Vitamin D): a steroid hormone that has final activation in the kidney and is necessary for regulation of calcium Porth, C. , & Marfin, G. (Eds. ). (2009). Pathophysiology: Concepts of altered health states (eighth ed. ). Philadelphia: Wolters Kluwer Health/ Lippincott Williams & Wilkins.

Function of the Kidney: �Generalized Stress response activation in the kidney o o o Control of vascular volume: regulation of renal blood flow is reliant on regulation of glomerular blood flow Renin-angiotensin II system: release of renin from kidney in response to SNS stimulation and release of epinephrine and norepinephrine then leads to the production of angiotensin II Aldosterone secretion: stimulated by high potassium levels in plasma, also by angiotensin II, transports sodium back into cells in order to increase potassium excretion. Lancaster, L. (Ed. ). (2001). Core Curriculum for Nephrology Nursing (4 th ed. ). Pitman, NJ: American Nephrology Nurses' Association

Renin Angiotension system ↓ renal blood flow ↓sodium at macula densa ↓afferent arteriole pressure epinephrine norepinephrine renin (from JGA) negative feedback loop ↓renin angiotensiogen angiotensin I ACE ↑ renal blood flow angiotensin II ↑ MAP peripheral vasoconstriction direct renal effects aldosterone (adrenal cortex) ↑ vascular volume renal tubular reabsorption Na+ and H 2 O

Function of the Kidney: �What is a function of the kidney? Production of erythropoietin That is correct Production of angiotensin II that is incorrect produced in the lung blood vessels Production of insulin That is incorrect produced by pancreas �What is key component of renal function? removal of waste products That is correct urination That is incorrect this is done by the bladder muscle movement That is incorrect

Basic Concepts of Renal Failure �“When 75 -80% of renal function is lost, the kidneys lose their ability to regulate the internal environment and all organ systems and physiologic processes are affected by renal failure” (Lancaster, 2001, p. 119) �“Uremia or the uremic syndrome refers to the constellation of signs, symptoms and physicochemical changes that occur with either acute or chronic renal failure. ” (Lancaster, 2001, p. 120) Lancaster, L. (Ed. ). (2001). Core Curriculum for Nephrology Nursing (4 th ed. ). Pitman, NJ: American Nephrology Nurses' Association

Basic Concepts of Renal Failure � Some Uremic Changes: � Fluid – electrolytes imbalances � fluid retention causing edema in legs, abdomen, and face � hyperkalemia, hypocalcaemia, hyperphosphatemia � Changes in cardiovascular system � Includes the RAAS due to decrease in renin production interrupting feedback loop � Changes in inflammatory –immune response � Altered T-cell function � Altered B-cell number and function � Accumulation of toxins � Urea � Creatinine � Uric acid � Beta 2 microglobulin Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Basic Concepts of Renal Failure �For more information on Chronic renal failure �See V. Kolmers power point �http: //faculty. alverno. edu/bowneps/MSN 621/MSNtut orialsindexfull. html

Multiple Myeloma Background

Multiple myeloma �Myeloma occurs in the B lymphocytes �Lymphocyte development stem cell very young b lymphocyte injury to DNA (unknown etiology) of a single cell in lymphocyte development more developed b lymphocyte other blood cell red cells white cells (other lymphocytes platelets Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org Fully developed antibody producing plasma cell other lymphocytes T lymphocytes natural Killer (NK) cells

What is Myeloma? �Overproduction of a single immunoglobulin by cancerous plasma cells �Immunoglobulin is “a protein produced by body’s immune system to help fight infections”(Bashey & Huston, 2005, p. 2) �Normally the body make many different types of immunoglobulins (polyclonal) �In Myeloma the cancerous cells are monoclonal and are usually of no use to the body �These cells are called M-protein and can be detected in urine. �Research is being done to look at the various reasons for these changes – especially at certain genetic variations (such as Chromosome 13 deletion) Bashey, A. , & Huston, J. (2005). 100 Questions & answers about myeloma. Sudbury, MA: Jones and Bartlett Publishers.

Immunoglobulin Molecule L L = Light Chains H = Heavy Chains H H L

Immunoglobulin Molecule �Breaks down into the heavy chains and light chains �Light chains are also called Bence Jones proteins �High amounts of light chains in the urine causes the most protein damage to the kidney

MM Background Clinical Features �Early MM – often asymptomatic �Common clinical features: �C – hyper-Calcemia �R – renal (kidney) problems �A – anemia �B – bone pain �Fatigue �Recurrent infections �Neuropathy micrcosoft clip art Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Myeloma Risk Factors �Clinical Risk Factors: �Black �Male = Female �Family history of MM �Median age at dx: 701, 2 � 7% before age 55 � 2% before age 40 � 0. 3% before age 30 1. Ries LAG, et al. SEER Cancer Statistics Review, 1975 -2004. National Cancer Institute. Bethesda, MD: Available at http: //seer. cancer. gov/csr/1975_2004. Accessed April 10, 2008. 2 Jemal A, et al. Cancer Statistics, 2008. CA Cancer J Clin 2008; 58: 71 -96 Slide used with permission from Dr. Thompson, WMH 2010

Myeloma risk factors: AGING �Disease of the elderly �risk of myeloma is 10 times greater in those 75 to 79 compared to those 45 to 50 �uncommon in people younger than 40 y/o �In short, higher age groups (especially after age 60 years)showed significantly risk of MM for both-sexes, men and women. (Khan, Mori, Sakauchi, Matsuo, Ozasa, & Tamakoshi, 2006, p. 579) �more often in African American than whites while Asians less likely than whites Khan, MMH. , Mori, M. , Sakauchi, F. , Matsuo, K. , Ozasa, K. , & Tamakoshi, A. (2006). Risk factors for multiple myeloma: Evidence from the Japan collaborative cohort (JACC) study. Asian Pacific Journal of Cancer Prevention, 7, 575 -581.

Renal Failure in Myeloma �Mechanism of inflammation and damage �Light chain cast deposition – tubule obstruction (“myeloma kidney”) by protein deposits �Obstruction of tubules by plasmacytoma �Hypercalcemia, hyperuricemia: both of which can cause inflammation in the tubules due to high concentrations �Renal amyloid: can cause obstruction which will cause inflammation in the glomerulus �Recurrent pyelonephritis chronic recurrent infections that lead to chronic inflammation of the basement membrane of the nephron tubule �May develop RTA 2 (Fanconi syndrome) Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Myeloma kidneycast nephropathy Figure: Pathogenesis of myeloma cast nephropathy. Ca 2 = calcium, THP = Tamm Horsfall Protein, GFR= glomerular filtration rate casts= protein breakdown of light chains in kidney can causes obstruction and injury to distal tubule Scheme used with permission of Dr. C. Winearls

The Myeloma kidney Used with permission from Dr. C. Winearls

Myeloma treatment v. RVD – Revlimid®-Velcade®dexamethasone v. VTD – Velcade®- thalidomidedexamethasone v. VAD – Velcade®-Adriamycin®Dexamethasone All these are high dose chemotherapy regimens that need monitoring in the elderly patient and in the renal insufficient patient

Multiple Myeloma treatment � Autologous stem cell transplant �procedure that the patient’s own stem cells to restore blood cells after intense chemotherapy �good response rates even including elderly patients �process involves �pt in remission due to chemotherapy �pt’s stem cells harvested and frozen �pt receives conditioning therapy �stem cells are thawed and reinfused into the pt �results start to show in 10 -14 days Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Multiple Myeloma treatment: �Another transplant type is allogeneic �This is when the stem cells come from a HLA matched donor (usually a sibling but not always) �This is called tissue typing and is used in many transplant procedures (not just stem cell transplantation) �The procedure is the same as for an autologous donation – just where the cells originate is different. �This treatment is in clinical trials

Multiple Myeloma Treatment Genetic �Research is being done looking at different genetic polymorphisms and their effects �maintenance treatment after high dose therapy (nuclear factor κB) (Vangsted et al. , 2009) �treatment of myelomic bone disease - (multiple single nucleotide polymorphisms) (Durie et al. , 2009) �the role of tumor necrosis factor α (Hideshima, Chauhan, Schlossman, Richardson, & Anderson, 2001) Durie, B. , Van Ness, B. , Ramos, C. , Stephens, O. , Haznadar, M. , Hoering, A. , Haessler, J. , . . . Shaughnessy Jr. , J. (2009). Genetic polymorphisms of EPHX 1, Gsk 3 B, TNFSF 8 and myeloma cell DKK-1 expression linked to bone disease in myeloma. Leukemia, 23, 1913 -1919. Hideshima, T. , Chauhan, D. , Schlossman, R. , Richardson, P. , & Anderson, K. (2001). The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene, 20, 4519 -4527. Vangsted, A. , Klausen, T. , Gimsing, P. , Anderson, N. , Abildgaard, N. , Grefersen, H. , & Vogel, U. (2009). A polymorphism in NFKB 1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high dose treatment with stem cell support. Haematologica, 94(9), 1274 -1282.

correct What animal represents the common clinical features of multiple myeloma ? Microsoft clip art C: hyper calcemia, R: renal failure, A: anemia, B: bone pain Try again

Key Assessment in Multiple Myeloma

Physical presentation �Anemia – due to ↑ myeloma cells in the bone marrow which leads to ↓ in RBC production �Bone loss- due to excitement of the osteoclasts by the cytokines secreted from the myeloma cells �Back pain – due to fractures in the vertebral body �Infection – due to immune system failure ; normal immunoglobulin production is severely suppressed �Fatigue – due to anemia Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemialymphoma. org

Labs and diagnostic tests �Bone Marrow Aspiration /biopsy – examines marrow cells for abnormalities (can also be done after treatment to check proportion of cancer cells killed by therapy) �CBC – to look for anemia �Serum protein electrophoresis- looks for M proteins �Urine tests – 24 hour testing for protein tests- light chains (Bence Jones protein) Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Labs and diagnostic tests �Genetic testing �Fluorescence in situ hybridization (FISH) looks at changes in the chromosomes of the myeloma cells �G-banding karyotyping arrangement of chromosomes of a cell to look for variations (number, size, shape, arrangement) �“Among top SNP variations […] were those associated with drug metabolism/detoxification/transport, (Van Ness et al. , 2008, p. 12) Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Labs and diagnostic tests �Imaging tests �X-rays �CT Scans �“X-rays and CT scans are used to see if there any holes, breaks or thinning of the bones” (Leukemia -Lymphoma Society, 2010) Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Labs and diagnostic tests �Imaging tests �PET scans �MRIs �“MRIs and PET scans look for changes to the marrow and pockets of myeloma cells” (Leukemia -Lymphoma Society, 2010) Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

What lab test is used to look for M Proteins CBC Try again Looks at anemia FISH Try again Looks at chromosomal changes Serum electrophoresis correct Urine tests Try again Looks at M proteins Looks at light chains

Medical and Nursing Interventions

Renal Failure in Myeloma �Prevention �Avoid NSAIDs : they can affect prostaglandin levels and cause a decrease in GFR �Avoid radiographic contrast: can cause damage in GFR �Avoid dehydration: watch diuretic use �Watch for hypercalcemia: high levels of calcium can cause damage to the nephrons Itano, J. , & Taoka K. (Eds. ). (2005). Core curriculum for oncology nursing (4 th ed. ). St Louis, MO: Elsevier Saunders

Interventions �Hypercalcemia / Bone Loss – �Encourage fluid intake �Daily weights : monitor fluid loss , muscle mass loss due to decrease activity �Maintain mobility level (consistent with pt’s activity level) �Watch for changes in heart rhythm – bradycardia �Watch for changes in nutritional status- nausea, vomiting, constipation Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Interventions �Hypercalcemia / Bone Loss – �Bisphosponates – Aredia® and Zometa® (Infusions), Boniva®, Fosamax®, Actonel® (oral) �Watch for osteonecrosis of the jaw (ONJ)– exposed bone in the oral cavity �Inform doctor of any pending invasive dental work �Hold medicine one month prior and do not resume till area completely healed Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Interventions �Hypercalcemia – � Prevention of ONJ �Encourage good oral hygiene �Encourage routine dental examinations �Have pt avoid invasive procedures Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Interventions �Fatigue / Anemia �Pace daily activities �Planned rest periods �Procit® / Aranesp® Injections if hemoglobin is less than 10 �Monitor patient for GI bleeding �Hematemesis �Tarry stool Burrows-Hudson, S. , & Prowant, B. (Eds. ). (2005). Nephrology nursing: Standards of practice and guidelines for care. Pitman, NJ: Anthony J. Jannetti Inc. Itano, J. , & Taoka K. (Eds. ). (2005). Core curriculum for oncology nursing (4 th ed. ). St Louis, MO: Elsevier Saunders

Interventions �Infections �Neupogen® / GCSF (granulocyte colony stimulating factor) – increase WBC �Platelet transfusions for low platelet levels Itano, J. , & Taoka K. (Eds. ). (2005). Core curriculum for oncology nursing (4 th ed. ). St Louis, MO: Elsevier Saunders

Interventions �Infections �Catheter dressing changes per policy �Monitor for signs and symptoms of infection �Fever (with or without chills) �Evaluate catheter site for signs of infection �Redness, swelling, drainage, warmth �Administer antibiotics as ordered Burrows-Hudson, S. , & Prowant, B. (Eds. ). (2005). Nephrology nursing: Standards of practice and guidelines for care. Pitman, NJ: Anthony J. Jannetti Inc.

Interventions � Pain Control �Watch NSAID intake �Lowers GFR �Pace activity with rest periods �Help find comfortable position due to back pain �Bisphonates may help with bone pain �Neurontin® / Lyrica® / B complex vitamin w/ folic acid – to help with neuropathic pain Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org

Interventions �In 20% of patients diagnosed with multiple myeloma have renal failure as a serious complication �Mortality rate in multiple myeloma patients with renal failure is approximately 30%. This is mainly due to septicemia and infections from a compromised immune system. Goldschmidt, H. , Lannert, H. , Bommer, J. , & Ho, A. (2001). Renal failure in multiple myeloma "the myeloma kidney": State of the art. Saudi Journal of Kidney Diseases and Transplantation, 12(2), 145 -150.

Interventions �Hemodialysis: �Assess patient pre treatment- weight, blood pressure, HR, RR, Temperature, edema, mental status, ambulation status �Evaluate patient for – headache, nausea, vomiting, fever, chills, bleeding, pain, insomnia, weakness, fatigue �Reassess patient post treatment for changes in blood pressure , HR, RR, weight, edema Burrows-Hudson, S. , & Prowant, B. (Eds. ). (2005). Nephrology nursing: Standards of practice and guidelines for care. Pitman, NJ: Anthony J. Jannetti Inc.

Interventions �Hemodialysis: �Monitor treatment – adjust during in response to pt changes during treatment �Administer medications as ordered �Include pt teaching regarding diet and fluid needs (a MM pt might have a lower fluid restriction due to RRF or due to fluid loss with nausea/ vomiting with chemotherapy) �Ask pt when last chemo treatment was – use chemo precautions with patient Burrows-Hudson, S. , & Prowant, B. (Eds. ). (2005). Nephrology nursing: Standards of practice and guidelines for care. Pitman, NJ: Anthony J. Jannetti Inc.

What Nursing Intervention helps with prevention of renal failure Monitor patient for GI bleeding Try again Encourage good oral hygiene incorrect Catheter dressing changes per policy Try again Avoid NSAIDs Correct

Case Study �Mr. C is a 68 year old black male who presents with back pain, fatigue, and recurrent urinary tract infections for 3 months. He is currently taking naproxysen sodium for pain relief, and has finished an antibiotic course of bactrim for the UTI �What lab tests would you consider for this patient?

Case Study ØCBC showed Ø WBC 3. 23, RBC 3. 26, HGB 10. 5, HCT 30. 1 ØBMP Results Ø Na 135, K+ 4. 1, CL 113, CO 2 21, Glucose 82, Bun 59, Creatinine 3, Ca 10. 5, ØUrinanalysis was positive for blood and protein

Case Study �With high serum calcium and protein in the urine, what would your next steps be? Further Labs Serum electrophoresis to look for light chains What Medicine additions or changes? Add bisphonates and hold NSAIDS What are nursing interventions? Increase fluid intake, plan activity with rest periods answers are just suggestions there can be other avenues to take

Case Study �Patient now complains of nausea, anorexia, edema on legs. A 24 hour creatinine clearance shows >2 mg/dl. Hemodialysis is started via a Left IJ permacath

Case Study �What special instructions should be included Infection control Keep catheter dry – no showers for bathing helps to prevent infections from water borne bacteria What Medicine additions or changes? Epogen should be added What are nursing interventions? Work with dietitian to adjust diet and fluid intake answers are just suggestions there are other avenues for further care

In Conclusion: �Multiple myeloma accounts for approximately. 88% of pts with ESRD according to the USRDS. (Gertz, 2005) �Early diagnosis and treatment of renal failure is key to decrease mortality in these pts. Gertz, M. (2005). Managing Myeloma Kidney. Annals of Internal Medicine, 143(11), 835 -836.

In Conclusion: �By helping the pt monitor diet, activity, infection control and pain management the nurse can influence the outcome of treatment. �Patient teaching is a major component of compliance to treatment – not only in the management of MM but in the management of renal failure

References � Bashey, A. , & Huston, J. (2005). 100 Questions & answers about myeloma. Sudbury, MA: Jones and Bartlett Publishers. � Burrows-Hudson, S. , & Prowant, B. (Eds. ). (2005). Nephrology nursing: Standards of practice and guidelines for care. Pitman, NJ: Anthony J. Jannetti Inc. � Durie, B. , Van Ness, B. , Ramos, C. , Stephens, O. , Haznadar, M. , Hoering, A. , Haessler, J. , . . . Shaughnessy Jr. , J. (2009). Genetic polymorphisms of EPHX 1, Gsk 3 B, TNFSF 8 and myeloma cell DKK-1 expression linked to bone disease in myeloma. Leukemia, 23, 1913 -1919. � Gertz, M. (2005). Managing Myeloma Kidney. Annals of Internal Medicine, 143(11), 835836. � Goldschmidt, H. , Lannert, H. , Bommer, J. , & Ho, A. (2001). Renal failure in multiple myeloma "the myeloma kidney": State of the art. Saudi Journal of Kidney Diseases and Transplantation, 12(2), 145 -150. � Hideshima, T. , Chauhan, D. , Schlossman, R. , Richardson, P. , & Anderson, K. (2001). The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene, 20, 4519 -4527. � Itano, J. , & Taoka K. (Eds. ). (2005). Core curriculum for oncology nursing (4 th ed. ). St Louis, MO: Elsevier Saunders.

References � Khan, MMH. , Mori, M. , Sakauchi, F. , Matsuo, K. , Ozasa, K. , & Tamakoshi, A. (2006). Risk factors for multiple myeloma: Evidence from the Japan collaborative cohort (JACC) study. Asian Pacific Journal of Cancer Prevention, 7, 575 -581. � Lancaster, L. (Ed. ). (2001). Core Curriculum for Nephrology Nursing (4 th ed. ). Pitman, NJ: American Nephrology Nurses' Association. � Leukemia -Lymphoma Society. (2010, March 4). Myeloma. Retrieved March 4, 2010, from The Leukemia & Lymphoma Society Web site: www. leukemia-lymphoma. org � Porth, C. , & Matfin, G. (Eds. ). (2009). Pathophysiology: Concepts of altered health states (eighth ed. ). Philadelphia: Wolters Kluwer Health/ Lippincott Williams & Wilkins. � Thompson, M. (2008, April). Medical complications of multiple myeloma. Power point presentation presented at the Educational Program (Pro Health. Care), Waukesha, WI.

References �Van Ness, B. , Ramos, C. , Haznadar, M. , Hoering, A. , Haessler, J. , Crowley, J. , Jacobus, S. , . . . Gupta, R. (2008). Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival. Biomed Cental Medicine, 6(26). Retrieved June 8, 2010, from Bio. Med Central Web site: www. biomedcentral. com �Vangsted, A. , Klausen, T. , Gimsing, P. , Anderson, N. , Abildgaard, N. , Grefersen, H. , & Vogel, U. (2009). A polymorphism in NFKB 1 is associated with improved effect of interferon- alpha maintenance treatment of patients with multiple myeloma after high dose treatment with stem cell support. Haematologica, 94(9), 1274 -1282. �Winearls, C. (1995). Acute Myeloma Kidney International, 48, 1347 -1361.