Dr WAQAR ASST. PROFESSOR INTERNAL MEDICINE MULTIPLE MYELOMA Dr WAQAR ASST. PROFESSOR INTERNAL MEDICINE

NORMAL SCENARIO Bone marrow contains WBCs, which fight infection (neutrophils, monocytes, lymphocytes) Two types of lymphocytes: T & B During infection, B lymphos. grow & mature into “plasma cells” which produce antibodies Normally, there are only few plasma cells but during infection they increase in number

NORMAL HEMATOPOEISIS

DEFINITON Multiple myeloma is a malignancy (cancer) of plasma cells in which there is too much production of plasma cells. These cells are abnormal & the antibodies which they produce are also abnormal ( don’t function well) The myeloma cells (abnormal plasma cells) produce IgG antibody which is called para- -protein & it is functionally abnormal. The total antibody level is high in M.M. but these antibodies are abnormal in function

WHAT HAPPENS IN M.M. Excess plasma cells excess IgG is produced so, increased IgG in the blood blood becomes thick ( hyperviscosity) Plasma cells replace other cells in the marrow so, low RBCs, platelets & other WBCs. Plasma cells activate the osteoclasts in the bones increased bone destruction bone pain, fractures & hypercalcemia Increased production of “light chains” of the anti- -body. These are called Bence --Jones proteins. They appear in the urine & damage the kidneys.

Signs & Symptoms M.M is a disease of old age ( 60 & above) Bone Pain & Fractures: Occurs due to increased bone destruction Spine is commonly affected &low back pain is the most common symptom Vertebral fracture can cause S/S of spinal cord compression. Long bones also affected. 2) Infections, anemia & thrombocytopenia( due to marrow infiltration by plasma cells) 3) Fever, wt. loss, weakness.

S/S contd. 4) S/S of hypercalcemia (mental status changes) 5) Renal failure & its S/S ( renal damage by “light chains” & hypercalcemia) ( remember, light chains are also called Bence-Jones proteins)

INVESTIGATIONS BLOOD: a) Anemia, low WBCs & low platelets b) High levels of IgG (paraprotein). This is seen by doing electrophoresis (serum protein electro-phoresis S.P.E.P. ) c) ESR is always very high d) Increased calcium & urea/creatinine e) High levels of beta-2 microglobulin ( it’s a protein) ( SPEP, ESR, Calcium, beta 2 microglobulin) 2) URINE: a) Bence-Jones proteins in the urine seen by electrophoresis ( Urine protein electrophoresis)

Result of S.P.E.P. Very high levels of gamma globulins (paraprotein)

Contd. 3) X-Rays: * Areas of bone destruction are seen (lytic bone lesions). Usually seen in the spine. * Fractures may be seen * Do X-rays of skull, limbs & spine 4) Bone marrow biopsy: * Shows excess plasma cells ( more than 10% cells in the marrow)

BONE MARROW PICTURE

LYTIC LESIONS IN THE SPINE

X-Rays showing lytic lesions Pelvis & femur SKULL ( pepper pot appearance)

Lytic lesions/ Fracture

TREATMENT Age < 65: * Chemotherapy + stem cell transplant 2) Age more than 65: * Only chemotherapy

TREATMENT Drugs used as chemotherapy are: * Melphalan * Prednisone * Thalidomide * Proteasome inhibitors 2) For bone pain due to lytic lesions: * Local Radiotherapy & dexamethasone 3) Other Supportive treatments: * Blood transfusion for anemia * Quick treatment of infections * Medicines called Biphosphonates are routinely given to prevent fractures.

Treatment contd 4) Stem cell transplant Generally speaking, the 5 year survival rate is 35%.

In summary, suspect M. M. if :. Old patient In summary, suspect M.M. if : * Old patient * Low back pain, fever, systemic S/S * Lytic bone lesions on X-Ray * High serum calcium

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