multiple mieloma dan pv

7/31/2019 Multiple Mieloma Dan PV

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Multiple Mieloma

A malignancy of plasma cells

Characterized :

replacement of the bone marrow by plasmacells (B cell)

bone destruction

paraprotein formation (monoclonal

Gammopathy / spike M immunoglobulin).


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How Plasma Cells Work

Develop from stem cells in bone marrow

Stem cells develop into B cells (B

lymphocytes)

Antigens enter body then B cells develop

into plasma cells

Produce antibodies


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Diagnostic Criteria

Major criteriaI. Plasmacytoma on tissue biopsy

II. Bone marrow plasma cell > 30%III. Monoclonal M spike on electrophoresis IgG >

3,5g/dl,

IgA > 2g/dl, light chain > 1g/dl in 24h urinesample

Minor criteriaa. Bone marrow plasma cells 10-30%

b. M spike but less than abovec. Lytic bone lesionsd. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl


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Diagnostic Criteria for Multiple Myeloma

Diagnosis:

I + b, I + c, I + d

II + b, II + c, II + d

III + a, III + c, I II + d

a + b + c, a +b + d


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Replacement of the bone marrow leads initially toanemia and later to general bone marrow failure.

Malignant plasma cells can form tumors(plasmacytomas) that may cause spinal cord

compression. Bone involvement causes bone pain, osteoporosis, lytic

lesions, pathologic fractures, and hypercalcemia.

The activation of osteoclast in myeloma

Very high paraprotein levels (either IgG or IgA) may

cause hyperviscosity. The light chain component of the immunoglobulin often

leads to renal failure (often aggravated byhypercalcemia).

Light chain components may be deposited in tissues as

amyloid

Patophisiology


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a monoclonal paraprotein, the distinction between myeloma andmonoclonal gammopathy of unknown significance (MGUS) must bemade. MGUS is present in 1% of all adults and 3% of adults over age 70

years.

MGUS is far more common than myeloma.

MGUS will have a monoclonal IgG spike less than 2.5 g/dL, and theheight of the spike remains stable

MGUS progresses to overt malignant disease, but this may take manyyears.

Myeloma is distinguished from MGUS by findings of replacement ofthe bone marrow, bone destruction, and progression.

Myeloma must be distinguished from reactive polyclonalhypergammaglobulinemia. Waldenstrom's macroglobulinemia, lymphomas, and primary

amyloidosis (with which it is commonly associated).

Differential Diagnosis


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Most commonly, patients require treatment at diagnosis

because of bone pain or other symptoms related to thedisease.

Chemotherapy: The combination of vincristine, doxorubicin (Adriamycin), and

dexamethasone (VAD)

melphalan as primary treatment in younger patients because ofthe lack of bone marrow and stem cell damage.

The combination of thalidomide plus dexamethasone is aseffective as VAD chemotherapy for initial disease control, and isbeing increasingly used.

The optimal initial therapy for patients under age 70

years with myeloma is autologous stem celltransplantation.

Allogeneic transplantation is potentially curative inmyeloma, but its role has been limited because of theunusually high mortality rate (40-50%) in myeloma

patients.

Definite Therapy


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Prognosis The median survival of patients with myeloma

has been 3 years The prognosis is affected by : high paraprotein

spikes, renal failure, hypercalcemia, or extensivebony disease.

(stage I) if the IgG spike is less than 5 g/dL,there is no more than one lytic bone lesion, andthere is no evidence of hypercalcemia or renalfailure. A median survival of 5-6 years.

(stage III) have an IgG spike greater than 7 g/dL,hematocrit less than 25%, calcium greater than12 mg/dL, or more than three lytic bone lesions.

A median survival of 1-2 years

Broader use of immunotherapy with allogeneictransplantation may improve the outlook further


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POLYCYTHEMIA VERAEssentials of Diagnosis

Increased red blood cell mass.

Splenomegaly.

Normal arterial oxygen saturation.

Usually elevated white blood count and platelet count.


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Causes of polycythemia

Spurious polycythemia

Secondary polycythemia

Hypoxia: cardiac disease, pulmonary disease,high altitude

Carboxyhemoglobin: smoking

Renal lesions

Erythropoietin-secreting tumors (rare)

Abnormal hemoglobins (rare)

Polycythemia vera


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General Considerations

acquired myeloproliferative disorder

overproduction of all three hematopoietic celllines, most prominently the red blood cells.

The hematocrit is elevated (at sea level) whenvalues exceed 54% in males or 51% in females(Table 13-15).

Must determine whether true polycythemia or

relative polycythemia exists. Normal values for red blood cell mass are 26-34

mL/kg in men and 21-29 mL/kg in women.


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Relative ("spurious") polycythemia presents in middle-aged men who are overweight and hypertensive (often

on diuretic therapy); the hematocrit is almost always lessthan 60%, and they have a high-normal red cell massand a low-normal plasma volume.

If the red blood cell mass is increased, it is necessary to

determine whether the increase is primary or secondary. Primary polycythemia (polycythemia vera) is a bone

marrow disorder characterized by autonomousoverproduction of erythroid cells.

Erythroid production is independent of erythropoietin,

and the serum erythropoietin level is low. In vitro, erythroid progenitor cells grow without added

erythropoietin, a finding not seen in normal individuals.


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Symptoms and Signs

Symptoms related to expanded blood volume and increased bloodviscosity.

Common complaints include headache, dizziness, tinnitus, blurredvision, and fatigue.

Generalized pruritus, especially following a warm shower or bath,may be a striking symptom and is related to histamine release

Epistaxis. This is probably related to engorgement of mucosal bloodvessels in combination with abnormal hemostasis due to qualitativeabnormalities in platelet function.

Sixty percent of patients are men, and the median age at

presentation is 60 years. Polycythemia rarely occurs in persons under age 40 years.


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Physical examination

Plethora and engorged retinal veins.

Sleen is palpable in 75% of cases but is nearly alwaysenlarged when imaged.

Thrombosis is the most common complication of

polycythemia vera and the major cause of morbidity anddeath in this disorder.

Thrombosis appears to be related to increased bloodviscosity and abnormal platelet function.

Uncontrolled polycythemia leads to a very high incidenceof thrombotic.

Paradoxically, in addition to thrombosis, increasedbleeding also occurs. (peptic ulcer disease).


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Laboratory Findings

The hallmark of polycythemia vera is a hematocrit above normal, attimes greater than 60%.

Red blood cell morphology is normal.

Red blood cell mass is elevated.

White blood count is elevated to 10,000-20,000/uL

platelet count is variably increased, sometimes to counts exceeding1,000,000/uL.

Platelet morphology is usually normal.

White blood cells are usually normal, but basophilia and eosinophiliaare frequently present.

The bone marrow is hypercellular, with panhyperplasia of all

hematopoietic elements. Iron stores are usually absent from the bone marrow

Vitamin B12 levels are strikingly elevated because of increasedlevels of transcobalamin III (secreted by white blood cells).

Overproduction of uric acid may lead to hyperuricemia.


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Differential Diagnosis

Spurious polycythemia, in which an elevated hematocrit is due tocontracted plasma volume rather than increased red cell mass

A secondary cause of polycythemia should be suspected ifsplenomegaly is absent and the high hematocrit is not accompaniedby increases in other cell lines.

Arterial oxygen saturation should be measured to determine ifhypoxia is the cause.

A smoking history should be taken; carboxyhemoglobin levels maybe elevated in smokers.

A renal CT scan or sonogram may be considered to look for anerythropoietin-secreting cyst or

Polycythemia vera should be differentiated from othermyeloproliferative disorders (ET, CML)


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Treatment

Phlebotomy. One unit of blood (approximately 500 mL) is removedweekly until the hematocrit is less than 45%; the hematocrit ismaintained at less than 45% by repeated phlebotomy as necessary.

myelosuppressive therapy is indicated. Indications include a highphlebotomy requirement, thrombocytosis, and intractable pruritus.

Alkylating agents have been shown to increase the risk to acuteleukemia

Hydroxyurea is now being widely used when myelosuppressivetherapy is indicated Anagrelide is used in treatment ofthrombocytosis and may prove valuable.

Low-dose aspirin (81-325 mg daily) has been shown to reduce therisk of thrombosis without excessive bleeding

Allopurinol may be indicated for hyperuricemia.

Antihistamine may be helpful for control of pruritus,.


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Prognosis

Polycythemia is an indolent disease with mediansurvival of 11-15 years.

The major cause of morbidity and mortality isarterial thrombosis.

Polycythemia vera may convert to myelofibrosisor to chronic myelogenous leukemia.

In approximately 5% of cases, the disorderprogresses to acute myelogenous leukemia,which is usually refractory to therapy.

multiple mieloma dan pv

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