Multiple myeloma - Paraproteinaemias

Paraproteinaemias

Multiple myeloma

Definition

Multiple myeloma is a malignant clonal proliferation of plasma cells.

Incidence

3 per 100,000.

Age

Most commonly diagnosed 60–65 years.

Sex

2M : 1F

Pathophysiology

There is expansion of a single clone of plasma cells that replace normal bone marrow and produce monoclonal immunoglobulins. Cleavage of these immunoglobulins result in the production of Fab and Fc fragments; the Fab fragment is termed the Bence-Jones protein and is found in the urine of patients with myeloma. If the antibody polymerises there may be hyperviscosity of the blood. There is also production of osteoclast stimulation factor causing lytic bone lesions, bone pain and hypercal-caemia. Incomplete immunoglobulins may precipitate in the tissues as amyloid. Renal damage may result from deposition of light chains, amyloid or hypercalcaemia.

Clinical features

Marrow infiltration results in anaemia, thrombocy-topenia and leucopenia.

Lytic bone lesions most commonly in the axial skeleton may result in pathological fractures and bone pain. Spinal cord compression occurs in approximately 10–20% of patients at some time during the course of disease. Hypercalcaemia causes thirst, polyuria, constipation and abdominal pain.

Renal failure.

Investigations

The diagnosis of myeloma is made if there are:

·        Bone marrow aspirate has at least 10–15% plasma cells.

·        Lytic lesions on skeletal survey.

·        Monoclonal immunoglobulins in the urine or blood. Other investigations include:

·        FBC may show signs of marrow infiltration anaemia, thrombocytopenia, leucopenia.

·        The ESR is raised if there is a serum paraprotein. Serum calcium may be raised.

·        Hyperuricemia due to increased cell turnover.

Management

Chemotherapy with single alkylating agents improves prognosis. High dose combination chemotherapy with or without haemapoetic progenitor cell transplantation is used in younger patients. Recently, thalidomide has been demonstrated to produce a significant response in 30% of patients whose disease progressed following other therapy. Supportive care includes blood transfusion, radiotherapy for localised bone pain, correction of hypercalcaemia with bisphosphonates and management of renal impairment.