Myeloma cancer - multiple myeloma symptom, treatment, prognosis

Myeloma is part of a spectrum of diseases characterized by the presence of a paraprotein in the serum that can be demonstrated as a monoclonal band on protein electrophoresis. The paraprotein is produced by abnormal, proliferating plasma cells that produce, most often, IgG or IgA and rarely IgD. The paraproteinaemia may be associated with excretion of light chains in the urine, which are either kappa or lambda; the excess light chains have for many years been known as Bence Jones protein.

Clinical features of Myeloma

Myeloma is a disease of the elderly, the median age at presentation being 60 years. It is a complex illness which represents the interrelationship between:

• bone destruction , often causing fractures of long bones or vertebral collapse (which can cause spinal cord compression), and hypercalcaemia
• bone marrow infiltration resulting in anaemia, neutropenia and thrombocytopenia, together with production of the paraprotein which may (rarely) result in symptoms of hyperviscosity
• renal impairment owing to a combination of factors - deposition of light chains, hypercalcaemia, hyperuricaemia and (rarely) in patients who have had the disease for some time, deposition of amyloid.

All of this is further complicated by a reduction in the normal immunoglobulin levels, contributing to the tendency for patients with myeloma to have recurrent infections.

Diagnosis of Myeloma ( thalidomide, smoldering myeloma )

In order to make a diagnosis of myeloma, patients must have two out of three diagnostic features:

• paraprotein or Bence Jones protein
• radiological evidence of lytic lesions
• an increase in bone marrow plasma cells.

Anaemia and renal failure at presentation used to be the two factors associated with a very poor prognosis, 50% of patients dying within 9 months. The availability of renal dialysis has reduced the impact of renal failure. In patients without these features at presentation, the median survival with treatment is of the order of 2 years. The serum ß 2 -microglobulin level carries independent prognostic significance, as does the clinical stage of the disease at presentation. Staging is performed according to the Durie-Salmon criteria into three stages, with stage I being the earliest and stage III the most advanced. With conventional treatment, the median survival for patients with myeloma may be 3-4 years. Younger patients receiving more intensive therapy may live longer.

Symptoms of Myeloma

• Bone pain - most commonly backache owing to vertebral involvement.
• Symptoms of anaemia.
• Recurrent infections.
• Symptoms of renal failure.
• Symptoms of hypercalcaemia.
• Rarely, symptoms of hyperviscosity and bleeding resulting from thrombocytopenia.

Treatment of Myeloma

Patients with myeloma may present with a number of symptomatic and life-threatening complications.

• Anaemia should be corrected and infection treated.
• Bone pain can be helped most quickly by radiotherapy.
• Pathological fractures may also be prevented by prompt orthopaedic surgery with pinning of lytic bone lesions seen on the skeletal survey.

Myeloma is generally regarded to be incurable; no known therapy, including allogeneic bone marrow transplantation, is associated with indefinite remission. There is some debate as to whether patients with stage I myeloma should be treated with chemotherapy, or whether they should merely be monitored. Chemotherapy with melphalan has not been shown to improve survival of stage I disease, but may prevent the onset of debilitating complications such as fractures. Patients with bony lesions, bone marrow failure and renal impairment should receive chemotherapy immediately.

The use of alkylating agents (melphalan or cyclophosphamide) given in conjunction with prednisolone has improved the median survival of patients with advanced stage myeloma from 7 months to 2.5 years. More intensive doxorubicin-containing regimens may improve response rates, and might improve survival. High-dose melphalan supported by autologous BMT or PBPC support in younger patients seems to result in longer periods of remission. Adjuvant interferon therapy following both standard chemotherapy and high-dose melphalan have been shown to prolong remission, but may not significantly improve overall survival.

More recently, thalidomide has been shown to prolong remissions in myeloma. The mechanism of action is unclear, and studies continue. In addition, bony complications may be reduced in patients in 'plateau phase' by long-term administration of bisphosphonates.

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