Hematology Lecture (10) (Multiple Myeloma) د. علاء الدين مظفر

Multiple Myeloma

Multiple Myeloma (myelomatosis) is a neoplastic monoclonal proliferation of bone marrow plasma cells, characterized by lytic bone lesions, plasma cell accumulation in the bone marrow and the presence of monoclonal protein in the serum and urine.

Myeloma is mainly a disease of the middle age and elderly. It is rare under 40 years.

The incidence is 4/100000/year.

Clinical Features:

  1. Bone pain (especially backache) and pathological fractures.
  2. Features of anemia: lethargy, weakness, dyspnea, pallor, tachycardia …..
  3. Repeated infections: these are related to deficient antibody production and in advanced disease to neutropenia.
  4. Features of renal failure &/or hypercalcemia: polydipsia, polyuria, anorexia, vomiting, constipation and mental disturbance.
  5. Abnormal bleeding tendency: myeloma protein may interfere with platelet function and coagulation factors. Thrombocytopenia occurs in advanced disease.
  6. Occasionally there is macroglossia, carpaltunnel syndrome, and diarrhea due to amyloidosis.
  7. In about 2% of cases there is hyperviscosity syndrome with purpura, hemorrhage, visual failure, CNS symptoms, neuropathies and heart failure.

Diagnosis:

This depends on three principal findings:

  1. In 98% of patients monoclonal protein occurs in the serum or urine or both. The serum paraprotien isIgG in⅔ of cases, IgA in⅓ of cases, with rare IgM or IgD or mixed cases.

In doubtful cases, follow up will show a progressive rise in paraprotien concentration in untreated myeloma. Normal serum immunoglobulins (IgG, IgA, and IgM) are depressed.

The urine contains Bence Jones protein in ⅔ of cases. This consist of free light chains, either Ҡ or λ (kappa or lambda), of the same type as the serum paraprotien. In 15% of cases, however Bence Jones protienuria is present without a serum paraprotien.

  1. The bone marrow shows increased plasma cells (usually > 30%) often with abnormal forms ((Myeloma cells)).Immunological testing shows these cells to be monoclonal B cells and to express the same immunoglobulin heavy and light chains as the serum monoclonal protein.
  2. Skeletal survey shows osteolytic areas without evidence of surrounding osteoblastic reaction in 60% of patients or generalized bone rarefaction in 20%. Pathological fractures are common. No bone lesions are found in 20% of patients.

Other Laboratory Findings:

There is usually anormochromic normocytic or macrocytic anemia. Rouleaux formation is marked in most cases. Neutropenia and thrombocytopenia occur in advanced disease. Abnormal plasma cells appear in the blood film in 15% of patients.

High Erythrocyte Sedimentation Rate (ESR) usually above 100 mm/hr.

Hypercalcemia occurs in 45% of patients. Serum alkaline phosphatase is normal except following pathological fractures.

Blood urea and serum creatinine are raised in most of the cases. Despite from Bence Jones protrienuria, hypercalcemia, uric acid, amyloid and pyelonephritis may all contribute to renal failure.

Low serum albumin occurs with advanced disease.

Serum β2-microglobulin (the light chain of HLA class I antigen) is a useful indicator of prognosis. It partly reflects renal function.

Prognosis:

The median survival is 2 years with a 20% 4 years survival. The most serious prognostic features are the blood urea level. Other bad prognostic features are:

Severe anemia,

Low serum albumin at presentation,

Heavy Bence Jones protienuria,

Increased β2-microglobulin levels.

1