Myeloma is a clonal B cell malignancy characterised by the expansion of plasma cells (B-lymphocytes differentiated to produce immunoglobulins) in the bone marrow. These plasma cells can secrete whole monoclonal immunoglobulins or just immunoglobulin light chains, which are known as paraproteins.
Myeloma accounts for 1% of malignancies world-wide, is most common over 60 years of age and rare below the age of 40.
The aetiology of Myeloma is still under question and may be caused by several genetic events. Dysregulated or increased expression of cyclin D (which controls cell cycle progression) is thought to be an early event in the development of Myeloma as well as chromosomal translocations. There are many identified translocations but the most common are the Myc and Ras oncogene mutations, though these are commonly mutated in other cancers as well.
Bone disease, a common presentation in Myeloma, is due to increased osteoclast activation and osteoblast inhibition. This produces the characteristic punched out lytic lesions on skull X ray particularly and also leads to the hypercalcaemia. Osteoclasts are stimulated by a variety of factors produced by the Myeloma cells, which include MIP-1a, RANK-L, VEGF, TNF-a and IL-6. These are pro-growth signals that increase cell turnover and activity. As the disease is osteoclastic in nature it is important to note that bone scans do not diagnose myeloma bone disease. This is because bone scans measure osteoblastic activity using radiolabelled mineral tracers, which are deposited by osteoblasts in response to lytic bone disease e.g. prostate cancer metastasising to bone. Thus bone scans identify sclerotic rather than lytic lesions.
Due to the wide array of symptoms that a Myeloma patient can develop they could potentially present to any speciality. It is important to note that 20% of patients are asymptomatic and that the paraproteinaemia is detected on routine testing.
Common presenting features:
Other rarer presenting fatures may include: amyloidosis (carpal tunnel syndrome, diarrhoea, macroglossia) and hyperviscosity syndrome (headaches, vision distubances, haemorrhages, neuropathies, heart failure, )
To diagnose myeloma the patient must have:
There is no conventional cure for Myeloma, so the mainstay of treatment is aimed at symptomatic relief and prolonging the length and quality of life. This is achieved by chemotherapy, stem cell transplantation if the patient is elligible and supportive therapy. A small number of younger patients have achieved remission or been cured by an allogeneic stem cell transplantation, which remains the best option for a cure.
Chemotherapy for patients that are not candidates for stem cell transplantation
The first line regime in these patients is often chemotherapy with Melphalan, Prednisolone and Thalidomide (MPT). The main actions of Thalidomide are to inhibit angiogenesis and to inhibit the growth and survival of the tumour cells. Thalidomide has numerous side effects such as constipation, sedation, rash and peripheral neuropathy. If it cannot be tolerated then it can be removed from the regime or Lenalidomide can be substituted.
Treatment for patients elligible for stem cell transplantation
If patients are elligible for a stem cell transplant then as many of the malignant plasma cells in the bone marrow need to be eradicated as possible. This is achieved by an initial 4-6 cycles of high dose Dexamethasone or Dexamethasone and Thalidomide chemotherapy. Stem cells are then harvested from the host if the patient is going to have an autologous stem cell transplant. This is followed by an intensive course of high dose Melphalan and then the patient will have the transplant. The stem cell transplant can be autologous (from the host) or allogeneic (from a donor). Autologous transplants are never curative but prolong life by an average of a year. Allogeneic transplants offer a 33% chance of a cure but are only generally available for patients under 50 years of age. Despite the reasonable chance of a cure, mortality related to allogeneic transplant remains high with a third of patients developing infections or graft vs. host disease.
Treatment of relapse
Bortezomib or Lenalidomide +/- Dexamethasone are both used in the management of relapse
Although the 5-year survival for Myeloma is improving, the prognosis is still poor with only 34% of patients surviving at 5 years. At present, the median survival with non-intensive chemotherapy is 3-4 years.
MGUS (monclonal gammmopathy of uncertain significance) is a premalignant condition where there is isolated paraproteinaemia without the accompanying plasma cell abnormalities found in myeloma, it is a diagnosis of exclusion following dection of a paraproteinaemia. The annual conversion rate from monoclonal gammopathy of undetermined significance (MGUS) to myeloma or another B cell malignancy is 1%.
The International prognostic index is used to determine the prognosis for Myeloma patients. This is based on the serum B2-microglobulin and albumin levels. Patients with a B2M >5.5mg/L and an Albumin of <35g/L generally have a poor survival.
Fastbleep © 2019.