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osteoblasts, which disrupts bone homeostasis
. For this reason, all patients with MM receive regular bisphosphonate therapy that acts to reduce osteoclast activity( by induced apoptosis or inhibiting osteoclast attachment to bone), thus reducing bone resorption. Patients on bisphosphonate therapy require monitoring for complications such as hypocalcaemia, hypophosphataemia, renal injury and the rare complication of osteonecrosis of the jaw.
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Box 3. Risk factors for progression of MGUS
A useful established model focuses on three main risk factors for progression:
1. Paraprotein greater than 15g / L. 2. Non-IgG paraprotein. 3. Serum free light chain ratio less than 0.26 or greater than 1.65.
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Hypercalcaemia occurs most com- |
Source: Rajkumar SV et al 2005 12 |
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monly at presentation, and patients | ||||
may experience confusion, weakness, |
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dehydration, constipation and, at high levels, arrhythmia. Acute management requires hospitalisation for IV fluids and bisphosphonate therapy.
The presence of MM in the marrow
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Table 5. Risk-stratification models to predict progression of monoclonal gammopathy of undetermined significance to myeloma or related disorders |
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impedes regular immune function, including reduced normal immunoglobulins( seen as hypogammaglobulinemia), impaired T-cell functions, and aberrant monocyte and macrophage function. 10 This, combined with treatment induced immunosuppression, puts patients at high |
Number of risk factors
0 risk factors 5 %
1 risk factor 21 %
2 risk factors 37 %
Absolute risk of progression at 20 years
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risk of infection. Ensure vaccinations are current in all patients, and those undergoing an autologous transplant |
3 risk factors 58 %
Source: Rajkumar SV et al 2005 12
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require a complete schedule of childhood |
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vaccinations. Patients undergoing intensive treatments will often be on prophylactic medications for opportunistic infections( such as trimethoprim with sulfamethoxazole for |
Figure 7. A CT skeletal survey demonstrating a vertebral body myeloma lesion with breach of the posterior cortex. |
detected by either an increasing quantity of paraprotein detected by SPE or increasing light chain imbalance( see box 3 and table 5). Patients deemed to have lower risks of pro- |
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Pneumocystis jirovecii pneumonia). |
gression can be monitored in the |
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Viral infections are common, particularly herpes zoster, Epstein-Barr virus and cytomegalovirus, so prophylaxis |
myeloma-defining events, they are called solitary plasmacytomas. These lesions require a biopsy to confirm |
condition is characterised by a serum paraprotein less than 30g / L or an abnormal free light chain( kappa |
50 or older, and about 5 % of those older than 70. 11 MGUS is frequently detected and given its high prevalence |
community by sequentially observing their paraprotein and serum free light chain levels and moni- |
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is often administered. Other bacte- |
they originate from plasma cells, and |
to lambda) ratio of less than 0.26 |
and the often non-specific presenting |
toring for end-organ complications |
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rial infections and ongoing hypogam- |
a bone marrow biopsy is also required |
or greater than 1.65, as well as the |
symptoms of MM, there is great diffi- |
as MM develops. |
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maglobulinemia may prompt the use of regular IV immunoglobulin to prevent recurrent infections.
Solitary plasmacytoma
Plasmacytomas are localised tumours
comprised of plasma cells, which can occur inside the bone or in soft tissue( extramedullary). When there are multiple bony lesions, it is termed MM.
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to demonstrate the absence of a clonal plasma cell disorder in the marrow. Solitary plasmacytomas are treated with focal radiotherapy or surgical resection.
MONOCLONAL GAMMOPATHY OF UNCERTAIN SIGNIFICANCE
AS alluded to earlier, MGUS is a pre-
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absence of myeloma-defining events and less than 10 % clonal plasma cells in the bone marrow. 7
In essence, this condition represents an asymptomatic disorder with a relatively low level of protein detected in the blood and the absence of significant complications. The clinical significance is difficult to determine and becomes increasingly so as we age and
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culty identifying those who will progress to myeloma. MGUS is associated with progression to MM at a rate of 1 % per year. 11 Yearly risk is a difficult number to conceptualise but the risk of malignancy for a 50-year-old patient with a 25-year life span is 25 %, and this risk does not diminish with time.
MGUS requires no treatment and the purpose of follow-up is to detect
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SMOULDERING MYELOMA
SIMILAR to MGUS, smouldering
myeloma is an asymptomatic clonal plasma disorder that is a precursor state of myeloma. The distinction between MGUS and SMM is that the latter has increased amount of paraprotein and / or a higher population on
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However, as these can occasionally |
malignant clonal plasma cell dis- |
the disease becomes more common. |
progression to myeloma as early as |
plasma cells in the bone marrow; both |
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occur as a single solitary lesion without |
order and precedes myeloma. The |
MGUS affects up to 3 % of people aged |
possible. Progression is usually first |
of these convey a significantly higher |
M protein levels( g / L) |
100
8
60
40
20
Asymptomatic
0
Active myeloma
MGUS SMM
Remission
Relapse
Symptomatic
Time
Relapse
|
Relapsed refractory |
Cancer Drug Resistance Open Access Review MYC inhibitors in multiple myeloma; 4. 842-65, 2021 / CC BY 4.0 / bit. ly / 4mETbkN |
Figure 8. The responserelapse pattern in multiple myeloma patients. Monoclonal gammopathies that undergo malignant transformation are likely to respond initially to the therapy and enter in remission. However, the disease eventually relapses, and the response becomes less durable until resistance appears, resulting in relapsed refractory myeloma. |