Perth Haematology :: Dr Steven Ward
Myeloma and Plasma Cell Disorders
MULTIPLE MYELOMA Waldenström's Macroglobulinaemia Amyloid
Myeloma is a cancer of the bone marrow plasma cells. The characteristic features are lytic bone lesions (fractures), accumulation of plasma cells and the presence of a paraprotein (abnormal monoclonal antibody).
Plasma cells in the marrow are part of the immune system. These cells produce antibody (to help kill invading bacteria).
§ The diagnosis relies on a cluster of features; as the individual features may be seen in other disorders
§ Paraproteins can be seen in lymphoma, Waldenstrom’s macroglobulinaemia, CLL, Primary Amyloid, heavy chain disease, CHAD or less commonly transiently.
§ Lytic bone lesions and fractures can be seen in solid tumours invading bone – prostate cancer or breast cancer
§ Myeloma requires:
§ Increased plasma cells in the marrow
§ Paraprotein (in serum or urine)
§ Bony lesions
§ Renal failure requires rehydration and treatment for gout
§ Hypercalcaemia (high serum Calcium) requires iv fluids, diuresis, and drugs to reduce the calcium (often biphosphonates – Aredia, Zometa, Bonefos)
§ Bone compression of the spine and spinal cord requires urgent neurosurgery, steroids and radiotherapy / chemotherapy
§ Bone pain due to lytic lesions often responds to radiotherapy
§ Anaemia – transfusion
§ Severe recurrent infections – antibiotics, regular immunoglobulin infusions
§ The type of therapy will depend on the patient’s age, general health, extent of myeloma and its complications.
§ Palliative therapy: This type of treatment is aimed at reducing or preventing the problems associated with myeloma without causing excessive side-effects of treatment. Treatment is not curative but aimed at providing a decent quality of life. Elderly patients with lots of additional medical problems would be best served by this approach.
§ Standard chemotherapy: This is used to bring the disease under control, but again without the prospect of cure. Substantial remission and good quality of life is often achieved but the disease becomes active eventually.
§ High-dose therapy (Stem cell transplant): This is reserved for younger patients who are fit enough to tolerate the treatment. Even in this group cure is rarely (if ever) achieved, but a long period of good life with the disease being dormant is possible.
Drug combinations used in Myeloma (some are used as initial treatment, some later in relapse):
§ Melphalan & prednisolone
§ Cyclophosphamide & prednisolone
§ VAD (Vincristine, Adriamycin and Dexamethasone)
§ CTD (Cyclophosphamide, Thalidomide, Dexamathasone)
§ Dexamathasone alone (high-dose pulsed)
§ Z-Dex (Idarubicin and Dexamethasone)
§ DT-PACE (Dexamethsaone, Thalidomide, carboPlatin, Adriamycin, Cyclophosphamide, Etoposide)
§ Thalidomide alone
§ Newer agents: Lenalidomide, Bortezomib (Velcade) are in clinical trials currently.
Stem cell transplantation is usually performed after 4 cycles of VAD chemotherapy; stem cells are mobilised using high-dose cyclophosphamide and G-CSF; then the myeloablative therapy is high-dose melphalan. See the section on Stem Cell Transplantation.
Outcomes are improving with the improvements in detecting disease, managing the complications of the disease as well as better drugs to treat the disease. The median survival is now 3 years (bear in mind many people with myeloma are elderly, with a short survival anyway), and extended with high-dose therapy.
Myeloma is not curable, but 70-90% of patients will respond well to initial treatment, with 40-50% achieving a complete response (no measurable disease). However relapse is inevitable. The time between treatment and relapse is good time without symptoms or problems usually. The timing of the relapse is highly variable. 15% of myeloma patients are alive after 10 years.
International Staging System for Multiple Myeloma
JCO 23:3412-3240; 2005
Recognised Prognostic Factors
Cytogenetic / FISH abnormalities & prognosis
Smouldering (indolent) Myeloma Diagnosis
(=Stage 1A Durie/Salmon)
Solitary Plasmacytoma of bone diagnosis