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risk of conversion of SMM into MM
when compared with MGUS.
SMM is defined by the presence
of a serum paraprotein 30g / L or greater, or a urinary monoclonal protein 500mg or greater / 24hours and / or 10-60 % clonal bone marrow plasma cells. 7 This again must occur without the presence of myeloma-defin-
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Box 4. Risk factors to predict the progression of SMM
1. Paraprotein greater than 20g / L. 2. Involved to uninvolved light chain ratio greater than 20. 3. Clonal bone marrow plasma cell infiltration greater than 20 %.
Source: Mateos MV et al 2020 15
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paraprotein, it is referred to as the more commonly known Waldenström macroglobulinaemia.
The presentation may be similar to that of patients with myeloma. However, because the of the IgM protein( that is usually present as a pentamer) hyperviscosity is significantly more likely, especially
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paraproteinemia. In one study, these lymphomas were estimated to have a paraprotein associated in 17 % of cases. 16
While usually diagnosed by the presence of a lymphocytosis, the lymphoproliferative disorder chronic lymphocytic leukemia( CLL) can be associated with a paraprotein
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lupus erythematous( the likely cause for her anaemia).
However, her initial investigations reveal an IgA kappa paraprotein of 21g / L( normally undetectable) with normal serum free light chains. She is referred to a haematologist who performs a bone marrow biopsy that finds 5 % clonal plasma cells. She has
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ing events. |
when the paraprotein is greater than |
and is infrequently diagnosed this |
no myeloma-defining events and is |
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The natural history of the disease |
60g / L. A minority of patients may |
way. In a study with 1500 patients, |
therefore diagnosed as having MGUS. |
is diverse and three patient populations are described. The first shows no progression of the disease state and resembles a stable MGUS, the second group slowly progresses to MM, and the third rapidly develops into overt myeloma within two years of diagnosis. 13 Unlike with MGUS, the risk of progression across all three |
Table 6. IMWG 20 / 20 / 20 model for risk stratification of smouldering myeloma
Number of risk factors
Low risk( 0 risk factors)
Risk of progression to myeloma in two years
6.2 %
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present with lymphadenopathy and
IgM and IgG paraproteins were esti-
MGUS affects up to 3 % of people aged 50 or older, and about 5 % of those older than 70.
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She has two risk factors( a paraprotein greater than 15g / L and a non- IgG paraprotein) and thus her risk of progressing to myeloma is 37 % in the next 20 years. 12
Case study two
Oliver, a 75-year-old male, is incidentally
found to have an acute
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groups decreases with time. The overall risk of progression is 10 % per year for the first five years( 50 % in five years), 3 % per year for the next five years( 65 % in 10 years), and 1 % per year thereafter( similar to the risk of progression from MGUS). 14
Multiple models have been developed to predict the progression of SMM. The International Myeloma Working Group( IMWG) 20 / 20 / 20 utilises three risk factors to estimate progression( see box 4 and table 6). As with MGUS, there is no evidence to suggest treatment of SMM
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Intermediate risk( 1 risk factor)
High risk( 2-3 risk factors)
17.9 %
44.2 %
Source: Mateos MV et al 2020 13
OTHER CONDITIONS ASSOCIATED WITH A PARAPROTEIN
Lymphoplasmacytic lymphoma
LYMPHOPLASMACYTIC lymphoma
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hepatosplenomegaly.
Diagnosis is usually made on
bone marrow or lymph node biopsy supplemented by genetic testing to identify the characteristic genetic mutation MYD88.
Other lymphomas and lymphoproliferative disorders
Paraproteins can also be associated
with a variety of lymphomas. While there have been cases of paraproteins associated with aggressive
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mated at 4.8 % and 10 % respectively in this condition. 17
CASE STUDIES
Case study one
ANNA, a 50-year-old female, sees
her GP complaining of feeling fatigued, experiencing myalgias and mild weight loss. Her initial FBC shows a mild normocytic anaemia with a Hb 100g / L( normal 120g / L or higher) and an MCV of 87fL( range 80-100fL). Her iron studies, folate and B12 are normal and she has no
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kidney injury on routine bloods ordered by with his GP. A urine dipstick shows no blood, no white cells but an elevated protein. He has no clear pre-renal injury and no new medications have been initiated.
A renal tract ultrasound does not demonstrate an obstructive cause, and his GP orders SPE and immune electrophoresis and a serum free light chain. No paraprotein is detected on electrophoresis; however, his kappa light chains are 2700mg / L and his lambda light chains are 15mg / L, resulting
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leads to a clinical benefit; follow up is based on monitoring for progression to myeloma. There are, however, |
is a malignant neoplasm comprising small B lymphocytes, plasmacytoid lymphocytes and plasma cells. |
lymphomas such as diffuse large B-cell lymphoma, overall, these more immature lymphomas rarely |
demonstrable blood loss. Her GP orders an SPE, immunoelectrophoresis and serum free |
in a ratio of 180( reference range 0.31 – 1.56).
A subsequent bone marrow
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ongoing clinical studies investigating |
It usually involves the bone mar- |
have an associated paraprotein. |
light chains to investigate another |
biopsy confirms an infiltrate of 34 % |
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early therapy for patients with high- |
row and sometimes the spleen and |
Non-Hodgkin’ s lymphomas that |
potential cause of anaemia. Anna |
clonal population of plasma cells. |
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risk SMM that may change practice in |
lymph nodes. When it occurs in com- |
originate from a mature B-cell are |
develops joint pain and she is sub- |
He is diagnosed with MM and rap- |
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the future. |
bination with an IgM monoclonal |
more likely to have an associated |
sequently found to have systemic |
idly progresses to treatment to prevent |
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further kidney injury. |