MULTIPLE MYELOMA
= malignant proliferation of a single clone of plasma cells (terminally differentiated B cell)
- The malignant cells secretes a monoclonal Ig (IgG, IgA, IgM) or light chain (it is filtered by kidney, known as Bence Jones protein in urine)
- Normal Ig production is suppressed
- Diffuse bone marrow infiltration
- Osteoclast activity increases resulting in bone reabsorption
- Amyloidosis affects 10% cases
INCIDENCE
5 per 100 000 (1% of all malignancies, 10-15% of all haematological malignancies)
About 13,200 cases were diagnosed in 2000, 11,200 died from the disease
CLINICAL PRESENTATION
- Age >40, mean age of 65, Male are more affected than females
- Lassitude – from anaemia, renal failure, dehydration
- Bone pain from osteolytic lesions & pathological fractures – affect 2/3 patients – back, sternum, ribs, long bones,
-persistent localised pain, precipitated by movement- lesion are
caused by proliferation of tumour cells, and activation of osteoclasts. Myeloma cells releases OAF (Osteoclast activating factor)
- Recurrent bacterial infections –neutropenia and hypogammaglobulinaemia – most common infections are pneumonia & pylonephritis
- Renal failure- hypercalcaemia, amyloid, hyperuricaemia, recurrent infections. Tubular damage assoc with light chains excretion- inability to concentrate urine and hyponatraemia.
- Anaemia (80%)
- Spinal cord compression from compression by tumour or vertebral collapse
- Polymerisation of monoclonal antibody occasionally results in hyperviscosity – visual disturbance, confusion, headache, retinopathy
- Abnormal bleeding – low platelet
- Peripheral neuropathy occurs with amyloidosis
- Hepatosplenomegaly – occasionally
many clinical feats of myelomae.g cord compression, pathological #, sepsis, hyperviscosity and hypercalcaemia presents in medical emergencies- need immediate management
INVESTIGATIONS
- FBC: normochromic normocytic anaemia
- Blood film: Rouleaux (RBC sticking together) and background Ig staining may be seen
- ESR
- Serum protein electrophoresis: monoclonal band and immunoparesis
- Urine: Bence-Jones protein (free Ig light chains)
- Skeletal survey: generalised osteopenia, “punched-out” lytic lesions, (pepper-pot skull: palpable), pathological fractures
- Bone marrow biopsy: >10% bone marrow are plasma cells
- Ca, Normal Alk Phosphatase
- Urate
- Renal failure
DIAGNOSIS CRITERIA: (1 major & 1 minor, or 3 minors)
Major- Plasmacytoma on biopsy (A discrete, presumably
solitary mass of neoplastic plasma cells in bone or in one of various extramedullary sites; in man, such lesions are probably the initial phase of developing plasma cell myeloma)
->30% plasma cells on bone marrow biopsy
-monoclonal band on electrophoresis>35g/L for IgG, 20g/l for IgA, or >1.0 of light chains excreted on urine per day
Minor- 10-30% plasma cells on bone marrow
-Abnormal monoclonal band but levels less than listed above
-Lytic bone lesions
-Immunosuppression (other Ig )
TREATMENT
- Observation in asymptomatic, uncomplicated disease
- Supportive Rx: antibiotics, transfusion, analgesics, correction of hypercalcaemia when needed (biphosphonates), plasmapheresis (remove light chains), Allopurinol
- Encourage high fluid intake
- Chemotherapy: Melphalan (alkylating agent) & high dose Prednisolone control symptoms and reduces tumour burden
- Combined chemotherapy (VAD) in refractory disease
- Radiotherapy on localised bone pain
- High-dose chemotherapy with autologous/allogeneic stem cell marrow transplantation in selected patients
- ? -interferon :prolongs duration of response, but highly toxic, and does not prolongs survival
PROGNOSIS
- median survival: 3 years
- Death from infection, renal failure, haemorrhage
- Poor prognostic factors are:
-2- microglobulin levels
- urea (>10mmol/L)
- haemoglobin (<7.5g/dL)
- age
- albumin