Supportive Treatment of Multiple Myeloma

Supportive Treatment of Multiple Myeloma

• Supportive treatment is the treatment that aim to treat the signs & symptoms or reduce them; it is not aim to treat the disease itself.

Renal Impairment :-

• Rehydrate.
• Treat the underlying cause (e.g. hypercalcemia, hyperuricemia).
• Dialysis.
• Drink at least 3 Liter of fluid daily (all multiple myeloma cases).

Bone disease and hypercalcemia :-

• Bisphosphonates (such as pamidronate, clodronate or zoledronic acid) reduce the progression of bone disease.
• Rehydration with isotonic saline, a diuretic and corticosteroids followed by a biphosphonate (to treat acute hypercalcemia).

Compression paraplegia :-

• Use decompression laminectomy or irradiation. 
• Also corticosteroid therapy may help.

Anemia :-

• Erythropoietin.
• Transfusion.

Bleeding (Bleeding caused by paraprotein interference with coagulation and hyperviscosity syndrome) :-

• May be treated by repeated plasmapheresis.

Infections :-

• Must treated rapidly.
• Prophylactic infusions of immunoglobulin concentrates together with oral broad - spectrum antibiotics and antifungal agents may be needed for recurrent infections.

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Multiple Myeloma: An Overview

Multiple Myeloma: An Overview

Definition:-

• Multiple myeloma (MM) is a malignant bone marrow–based, plasma cell neoplasm associated with abnormal protein production.

• Multiple myeloma also called myelomatosis.

Epidemiology:-

• 1~2% of all types of malignant diseases
• ~10% of hematological malignancies.
• 15% of lymphoid malignancies.
• ~ 50 cases per million.
• Twice common in black than white people.
• Slightly more common in males than in females.
• 98% of cases occur over the age of 40 years with a peak incidence in the 7th decade.

Etiology (Causes):-

- Exact cause is unknown, but the following are suspects:

• Radiation.
• Viral infections.
• Toxins.
• Chemicals.
• Chromosomal abnormalities ( 8 % - 35 % of MM patients ).

- MM patients with chromosomal damage have a worse prognosis, a higher rate of disease acceleration, and decreased survival. 

Clinical Signs & Symptoms:-

• Fatigue: caused by anemia
• Excessive thirst and urination: caused by excess calcium.
• Nausea: caused by excess calcium.
• Bone pain in back and ribs: caused by plasma cell acceleration.
• Bone fractures: caused by calcium leeching from bones into circulation.
• Unexpected infections: caused by compromised immunity.
• Weakness and numbness in the legs: caused by vertebrae compression. 
• Renal insufficiency.(Myeloma kidney).
• Hypercalcemia.
• Amyloidosis (in 5% of cases).
• Weight loss & night sweats (in advanced cases).
• Abnormal bleeding tendency: myeloma protein may interfere with platelet function and coagulation factors
• Thrombocytopenia (in advanced cases).

Laboratory Findings:-

• Anemia (2/3 of cases). ( Normocytic normochromic anemia ).
• Leukopenia (1/3 of cases).
• Thrombocytopenia.
• ESR > 100 mm/hr.
• Blood film shows rouleaux with a bluish background staining.
• Bone marrow shows >10% plasma cells.
• ↑ Total protein.
• ↑ Uric Acid.
• ↑ LDH.
• Hypercalcemia.
• Protein electrophoresis (monoclonal spike in the gamma region).
• Bence-Jones protein (immunoglobulin light chain) in urine. (in some cases).
• Serum β₂ microglobulin (β₂M) often raised and higher levels correlate with worse prognosis.

Radiology:-

X-rays, CT scan, MRI or PET.

Prognostic Data:-

Prognostic data include:-

• Hb.
• β₂M.
• Creatinine.
• Albumin. &
• Extent of skeletal disease.

Treatment:-

• Chemotherapy.
• Supportive.
• Radiation.
• Transplantation (bone marrow; stem cell).

Prognosis:-
 

• The prognosis of MM is poor.
• Median survival of only 6 months without therapy.
• The median survival can be increased to 3 years with chemotherapy.
• Increased survival has been reported with autologous bone marrow & peripheral blood stem cell transplants.
• Infection is a major cause of death.

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Hemophilia: An Overview

Hemophilia A (Classic Hemophilia; Factor VIII Deficiency)

Ø   The most common inherited coagulation disorder (after Von Willebrand Disease).

Ø     The factor VIII gene is on the X chromosome so inheritance is sex-linked with the severe disease occurring in males.

Ø     Hemophilia A accounts for 80–85% of all cases of hemophilia with a prevalence of approximately 1 in 5,000–10,000 male births.

Ø     Genetic changes of the factor VIII gene.

Ø     Each son has a 50% chance of inheriting the affected gene.

Ø     Approximately 30% of the affected individuals have no positive family history of the disease.

Clinical Features

Ø     These range from severe spontaneous bleeding, especially into joints (hemarthroses) and muscles, to mild symptoms, depending on the factor VIII level.

Ø     Generally individuals with > 30% activity do not have hemophilia symptoms.

Ø     Onset in early childhood (e.g. post-circumcision).

Ø     Pseudotumours as a result of extensive bleeds.

Ø     Hemarthrosis (usually in severe cases) is the most common feature of severe hemophilia.

Ø     Joint bleeds, particularly into the knee and ankle.

Ø     Chronic debilitating joint disease caused by repeated bleeds.

Ø     Increased risk of post-operative or post-traumatic hemorrhage.

Ø     Subcutaneous hematomas can begin with slight trauma and spread to involve a large mass of tissue, causing purple discoloration of the skin.

Ø     Epistaxis is rare in hemophilia.

Ø     Hematuria.

Ø     Deep muscle bleeding.

Ø     Excess bleeding from dental extractions.

Ø     Bleeding with intramuscular injections.

Ø     Delayed bleeding after minor cuts.

Ø     The most common cause of death (after exclusion of viral infections transmitted by the replacement product) is intracranial hemorrhage, which can occur spontaneously or after trauma.

Ø     Mild deficiencies can be asymptomatic and unsuspected until a surgical procedure or major traumatic injury results in severe bleeding.

Laboratory Data

Ø     APTT >> ↑

Ø     PT >> N

Ø     PFA-100 test >> N

Ø     Plasma Factor VIII >> ↓

Ø     Von Willebrand factor (vWF) >> N

Ø     Carriers have factor VIII levels in plasma approximately 50% of normal. If the levels are <40% they may have clinical features of mild hemophilia. DNA analysis is helpful in carrier detection and antenatal diagnosis.

Treatment

Ø     Infusions of factor VIII (either recombinant or concentrate from normal donated plasma “Cryoprecipitate”).

Ø     Avoid aspirin, other antiplatelet drugs and intramuscular injections.

Ø     Gene Therapy.

Complications of Treatment

Ø     Infections.

Ø     Neutralizing antibodies (inhibitors) to factor VIII in 15% of severe patients may require:

§        Immunosuppressive therapy,

§        Treatment with porcine factor VIII, or

§        Plasma exchange.

Hemophilia B  (Factor IX Deficiency; Christmas Disease)

Ø     15–20% of hemophilia.

Ø     ~1 in 30.000 males.

Ø     Factor IX is coded by a gene close to the gene for factor VIII.

Ø     Specific Factor IX Assay.

Ø     Bleeding episodes are treated with high - purity factor IX concentrates. Because of its longer biological half-life, infusions do not have to be given as frequently as do factor VIII concentrates in haemophilia A.

Ø     Recombinant factor IX.

Ø     Gene Therapy.

Ø     Clinical features & other laboratory data are same as in hemophilia A.

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