Multiple Myeloma Dimas Bayu

Definition

!  Multiple myeloma : as myeloma or plasma cell myeloma

!   cancer of the Plasma Cell

!  Multiple myeloma !   excessive numbers of abnormal plasma

cells in the bone marrow

!   overproduction of intact monoclonal immunoglobulin (IgG, IgA, IgD, or IgE) or Bence-Jones protein (free monoclonal κ and λ light chains)

Definition

!  Normal Plasma Cell Function in the Immune System !   Stem cells can develop into B

lymphocytes -- >travel to the lymph nodes, mature, and then travel throughout the body.

!   When foreign substances (antigens)

enter the body -- >B cells develop into plasma cells that produce immunoglobulins Ig (antibodies) to help fight infection and disease.

Figure legend: In multiple myeloma, the B cell is damaged and gives rise to too many plasma cells (myeloma cells). These malignant cells do not function properly and their increased numbers produce excess single type immunoglobulins that the body does not need along with reduced amounts of normal immunoglobulins.

!   These myeloma cells travel through the bloodstream and collect in the bone marrow, where they cause permanent damage to healthy tissue.

!   As tumors grow, they invade the hard outer part of the bone, the solid tissue.

!   In most cases, the myeloma cells spread into the cavities of all the large bones of the body, forming multiple small lesions. This is why the disease is known as "multiple" myeloma.

Incidence

!  Multiple myeloma is the second most prevalent blood cancer after non-Hodgkin's lymphoma

!   1% of all cancers and 2% of all cancer deaths.

!   Age 60-65 years most common

!  Occurs in men > women

!   African Americans and Native Pacific Islanders have the highest reported incidence of this disease and Asians the lowest

Causes

!   Genetic causes !   Ongoing research is investigating whether

HLA-Cw5 or HLA-Cw2 may play a role in the pathogenesis of myeloma.

!   Environmental or occupational causes !   significant exposures in the agriculture,

food, silicon ,Benzene, Nickel and petrochemical industries

!   Radiation: !   Radiation has been linked to the

development of myeloma. !   In 109,000 survivors of the bombing of

Nagasaki, 29 died from myeloma from 1950-1976; however, some recent studies do not confirm that these survivors have an increased risk of developing myeloma.

Clinical features

!  common tetrad of multiple

myeloma is CRAB

C = Calcium (elevated)

R = Renal failure

A = Anemia

B = Bone lesions

Clinical Features

!  Bone pain !   Myeloma bone disease -- >proliferation

of tumor cells and release of IL-6 <osteoclast activating factor :OAF>-- >stimulates osteoclast to break down bone-- > leading to hypercalcemia

!   These bone lesions in plain radiographs-- > "punched-out" / lytic bone lesion

Clinical features

!  Bone pain !   Myeloma bone pain -- > involves the

rib ,sternum, spine , clavicle , skull , humerus & femur

!   The lumbar vertebrae are one of the most common sites of pain -- >may lead to spinal cord compression.

!   Persistent localized pain may indicate a pathological fracture

Clinical features

Clinical features

Clinical features

Clinical features

! Hypercalcemia !   Pt. present with confusion, somnolence,

bone pain, constipation, nausea, and thirst.

!   Anemia

!   The anemia :normocytic and normochromic.

!   It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines.

Clinical features

!   Bleeding !   bleeding resulting from thrombocytopenia.

!   In some patients, monoclonal protein may absorb clotting factors and lead to bleeding, but this development is rare.

! Hyperviscosity !   Malignant plasma cells excretes an abnormal

M protein (Para-protein) !   high volume of monoclonal protein -- >

blood viscosity increases-- >complications such as stroke, myocardial ischemia, or infarction.

Clinical features

!   Infection

!   Organism : polysaccharide encapsulated <strep.pneumoniae, H.influenzae>

!   Common pneumonia pathogens :S pneumoniae, S aureus, and K pneumoniae

!   Common pathogens causing pyelonephritis : E coli and other gram-negative organisms.

!   The increased risk of infection is due to

immune deficiency resulting from diffuse hypogammaglobulinemia which is due to decreased production and increased destruction of normal antibodies.

Clinical features

!   Renal failure !   Renal failure may develop both acutely

and chronically. !   It is commonly due to hypercalcemia. !   It may also be due to tubular damage from

excretion of light chains, which can manifest as the Fanconi syndrome (type II renal tubular acidosis).

!   Other causes include glomerular

deposition of amyloid, hyperuricemia, recurrent infections (pyelonephritis), and local infiltration of tumor cells.

Clinical features

!   Neurological symptoms !   Common problems are weakness, confusion

and fatigue due to hypercalcemia. !   Headache, visual changes and retinopathy

may be the result of hyperviscosity of the blood depending on the properties of the paraprotein

!   Finally, there may be radicular pain, 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).

!   It may give rise to paraplegia in late presenting cases.

Lab Findings

•  Anemia ( normochrom )

•  Rouleaux Formation

•  Very High ESR (eg. 150 / 160 )

•  Hypercalsemia

•  Proteinuria (Bence Jones protein)

n  Abnormal Electrophoresis protein

(monoclonal Spike on beta or gamma)

Rouleaux Formation

Protein Serum Electrophoresis

Normal Monoclonal Protein in Myeloma

Kyle RA and Rajkumar SV. Cecil Textbook of Medicine, 22nd Edition, 2004

Diagnostic Criteria for MM

M Spike on SPEP

Malignant Plasma on BMP

CRAB

MGUS + Less than 10%

-

Smoldering Myeloma

+ 10% & more -

Multiple Myeloma

+ 10% & more +

Management

n  1. Symptomatic (bone-pain, etc)

n  2. Melphalan/Alkeran + prednisone (alkylating)

n  3. Local Radio tx

n  4. Avoid prolonged immobilization

n  5. Avoid dehidration

Prognosis

n  Median survival : 3 yrs

n  Worsen in : very high paraprotein spikes, renal failure, hypercalsemia & extensive bone lessions

n  High Tumor Burden :

spike IgG > 7 g/dl

hematocrite < 25 %

ca serum > 12 mg/dl

bone lession > 3 location

è median survival 1 yr

Summary !   Consider MM in elderly patients with new

onset bone pain/fatigue/CRAB symptoms not resolving with treatment

!   Basic work up: SPEP/UPEP (+/- immunofixation), CBC, peripheral smear, BUN/CR, Ca, skeletal survey

! DDx, MGUS, asymptomatic vs symptomatic, Waldenstrom’s, Amyloidosis, NHL, etc..

!   No Tx for MGUS and asymptomatic MM.

!   Manage Complications: Bisphosphonates, orthopedics referral PRN, Vaccination, CRAB.

SKDI revisi 2012

!  MYELOMA MULTIPEL berada pada area kompetensi 1

!   Tingkat Kemampuan 1: mengenali dan menjelaskan

!   Lulusan dokter mampu mengenali dan menjelaskan gambaran klinik penyakit, dan mengetahui cara yang paling tepat untuk mendapatkan informasi lebih lanjut mengenai penyakit tersebut, selanjutnya menentukan rujukan yang paling tepat bagi pasien.